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Tissue scaffold engineering technology can eliminate the impediments in revision surgery. A decent understanding of the mechanical compression properties of biomaterials is required for producing increasingly suitable materials for their use as tissue engineering scaffolds. The biomaterial must not only possess structural integrity but also appropriate biodegradability with sufficient sustainability. This study presents a numerical simulation method and the material behavior results that quantify the mechanical compression properties of a polycaprolactone (PCL) cube-cell model using the finite element method (FEM). The main interest of this study is to observe and quantify the quasi-static compression behavior and the effective thermal conductivity of the PCL scaffolds. It is modeled as such as it undergoes degradation due to surface erosion by the body fluid onto the scaffold. The effective elastic modulus, 0.2% offset yield stress, plateau stress and effective thermal conductivity were evaluated numerically. Results show a phenomenologically decreasing trend of these general properties for PCL scaffolds computed by numerical methods. The volumetric decrease in PCL promotes weakening of the scaffold at its strut causing failure under compression. The effective thermal conductivity decreases as the volume decreases due to the lower PCL substance possessed in the unit cell, which is naturally a thermal insulator. [ABSTRACT FROM AUTHOR]

Hydrogel 3D printing holds immense potential in fields like personalized medicine, regenerative therapies, and organ creation, offering biocompatible structures similar to the extracellular matrix. Gelatin‐Methacryloyl (GelMA) emerges as a promising candidate, while its high viscosity poses a significant challenge, especially in vat photopolymerization‐based 3D printing. Here, a new approach is presented by using Hofmeister ionic effect to substantially reduce the viscosity of high‐content (up to 60%) Gelatin bioink at room temperature with enhanced mechanical performance of the printed structures. The thinning effect induced by chaotropic Hofmeister ions is investigated through complex viscosity analysis, optical rotation measurements, and sol–gel conversion studies. The thinning effect induced by chaotropic ions enables precise 3D printing of Gelatin hydrogel, achieving accuracy comparable to prints made with polymers. Furthermore, after polymerization, the cations of the chaotropic salt change their role to cross‐linkers, leading to stronger scaffolds that exhibit biocompatibility with robust cell attachment, proliferation, and suitability for cell growth. The combination facilitates the creation of customizable structures and high printing accuracy will promote the wide application of Gelatin in the development of patient‐specific implants, drug delivery systems, and tissue scaffolds, further improving medical treatment efficacy and personalized healthcare. [ABSTRACT FROM AUTHOR]

Biodegradable polymers such as polylactic‐co‐glycolic acids (PLGA) are used for various implantable devices such as tissue scaffolds, drug delivery devices, and biosensors in different forms. However, high‐resolution patterning of biodegradable polymers on implantable devices has not been explored much yet. While electrohydrodynamic printing (EHD) can achieve high‐resolution printing compared to other printing methods, EHD printing of PLGA solutions is rarely attempted due to unstable printing. Such printing instability originates from the volatile nature of PLGA inks, and it causes nozzle clogging or change of ink conditions during printing. Here, PLGA ink formulation and a voltage input profile are studied for stable and high‐resolution EHD printing. Addition of glycerol at an optimal ratio as well as the control of voltage pulse shape strongly influenced both the stability and resolution of EHD printing of PLGA patterns. With the optimized inks and voltage inputs, stable printing of PLGA micropatterns down to 5 µm is achieved on both conductive and insulating surfaces for controlled drug release. Furthermore, use of a ring type electrode allows for EHD printing of PLGA micropatterns on 3D surfaces of PLLA tubes and stent struts. [ABSTRACT FROM AUTHOR]

Background: With the rapid growth of the ageing population, chronic diseases such as osteoarthritis have become one of the major diseases affecting the quality of life of elderly people. The main pathological manifestation of osteoarthritis is articular cartilage damage. Alleviating and repairing damaged cartilage has always been a challenge. The application of cartilage tissue engineering methods has shown promise for articular cartilage repair. Many studies have used cartilage tissue engineering methods to repair damaged cartilage and obtained good results, but these methods still cannot be used clinically. Therefore, this study aimed to investigate the effect of incorporating nerve growth factor (NGF) into a silk fibroin (SF)/chitosan (CS) scaffold containing bone marrow-derived mesenchymal stem cells (BMSCs) on the repair of articular cartilage defects in the knees of rabbits and to explore the possible underlying mechanism involved. Materials and methods: Nerve growth factor-loaded sustained-release microspheres were prepared by a double emulsion solvent evaporation method. SF/CS scaffolds were prepared by vacuum drying and chemical crosslinking. BMSCs were isolated and cultured by density gradient centrifugation and adherent culture. NGF-SF/CS-BMSC composites were prepared and implanted into articular cartilage defects in the knees of rabbits. The repair of articular cartilage was assessed by gross observation, imaging and histological staining at different time points after surgery. The repair effect was evaluated by the International Cartilage Repair Society (ICRS) score and a modified Wakitani score. In vitro experiments were also performed to observe the effect of different concentrations of NGF on the proliferation and directional differentiation of BMSCs on the SF/CS scaffold. Results: In the repair of cartilage defects in rabbit knees, NGF-SF/CS-BMSCs resulted in higher ICRS scores and lower modified Wakitani scores. The in vitro results showed that there was no significant correlation between the proliferation of BMSCs and the addition of different concentrations of NGF. Additionally, there was no significant difference in the protein and mRNA expression of COL2a1 and ACAN between the groups after the addition of different concentrations of NGF. Conclusion: NGF-SF/CS-BMSCs improved the repair of articular cartilage defects in the knees of rabbits. This repair effect may be related to the early promotion of subchondral bone repair. [ABSTRACT FROM AUTHOR]

Collagen is one main component of the extracellular matrix (ECM) in natural tissues and is, therefore, well suited as a biomaterial for tissue engineering. In this study, a method is presented to 3D‐bioprint collagen into a precipitation bath comprising recombinantly produced spider silk protein eADF4(C16) yielding a composite with excellent mechanical properties. The spider silk precipitation bath induced assembly of the collagen into fibrils, and subsequent addition of potassium phosphate buffer lead to the formation of silk particles and stabilization of the collagen fibrils. The produced collagen‐silk composite scaffolds show an internal structure of homogeneously distributed and interacting collagen fibrils and spider silk particles with significantly better mechanical properties compared to plain collagen scaffolds. Further, enzymatic degradation assays of the scaffolds over a 7‐day period show higher stability of the collagen‐silk scaffolds compared to plain collagen scaffolds in the presence of wound proteases. Using the spider silk variant eADF4(C16‐RGD) further increases compressive stress and elastic modulus compared to that of the unmodified variant. Finally, it is shown that the unique collagen‐spider silk composite scaffolds comprising the cell‐binding domains of collagen and the RGD sequence in the spider silk variant represent a promising material for soft tissue regeneration. [ABSTRACT FROM AUTHOR]

Regenerative biomedicine has emerged as a forefront area in medical research, heralding a new era of therapeutic strategies. This review delineates the integration of 2D materials (2DMs) within the area of biomedical engineering, leveraging their superior physicochemical attributes for enhance biomedical outcomes. The synergistic interaction between biomacromolecules and 2DMs is explored, demonstrating their potential to mitigate the limitations inherent to each while simultaneously augmenting their beneficial properties. In particular, incorporating 2DMs into hydrogels highlights their capability to enhance the mechanical strength of hydrogels, providing a biomimetic scaffold for tissue engineering regeneration and cancer diagnosis and therapy. An overview of the synthetic methodologies are provided for 2DMs, elucidating their interaction dynamics with biomacromolecules. The review primarily concentrates on the applications of biomacromolecule‐reinforced 2DM hydrogels across various biomedical fields, including bone tissue engineering, wound healing, neural tissue engineering, cardiac tissue engineering, as well as in the delivery of drugs and genes, cancer therapy, and biosensing technologies. Finally, the review discusses the existing challenges and future outlook for developing and using biomacromolecule‐reinforced 2DM hydrogels, underlining their transformative potential in regenerative medicine. [ABSTRACT FROM AUTHOR]

The regeneration of bone tissue is a complex process requiring innovative biomaterials with enhanced osteogenic properties to facilitate successful tissue engineering. Herein, a 3D bionic scaffold comprised of covalently bound graphene/carbon nanotube monoliths are present (3DGp/CNTs) exhibiting long‐range ordered porous characteristics, showcasing promising attributes for bone tissue applications. The lightweight, all‐carbon scaffolds not only demonstrate excellent mechanical performance in the hydrated state but also mimic the structural and functional features of the extracellular matrix, actively promoting cellular adhesion, proliferation, and differentiation. Significantly, the osteogenic differentiation of dental pulp stem cells (DPSCs) is observed, as evidenced by the upregulation of RUNX2, OSX, BSP, ALP, OPN, and OCN expression. This notable outcome can be attributed to the synergistic effect of 3DGp/CNTs, which create a conducive microenvironment for DPSCs and promote osteogenic differentiation by activating the BMP pathway. This observation elucidates the mechanism through which 3DGp/CNTs induce DPSC mineralization. The combination of these advantages, along with its straightforward and cost‐effective preparation technique, positions 3DGp/CNTs as a promising candidate for dental clinical engineering. [ABSTRACT FROM AUTHOR]

The biophysical heterogeneity of the bone–cartilage interface requires complex materials to mimic differences in bone density, extracellular matrix composition, and mineralization. Biomaterial approaches to repair osteochondral tissue typically use multilayer scaffolds, which require multistep fabrication and may undergo delamination at the construct interface. This work describes the development of functionalized microgels for the repair of osteochondral tissues using an N‐cadherin peptide, bone morphogenetic protein‐2 (BMP‐2) peptide, and changes in stiffness to create pro‐osteogenic and prochondrogenic microgels. Microgels, when annealed into a scaffold, outperforms bulk hydrogel controls evidenced by upregulation of osteogenic and chondrogenic markers in mesenchymal stromal cells (MSCs). The macroporous void space present in microgel anneals scaffolds enabled robust cell proliferation and extracellular matrix (ECM) deposition throughout the entire scaffold. A bilayer functionalized annealed microgel scaffold is then created and the ability to spatially control the differentiation of MSCs is assessed. Osteochondral bilayer scaffolds exhibit distinct regions of osteogenic and chondrogenic protein expression as a function of microgel population upon immunostaining for osteocalcin and aggrecan, respectively. Spatial transcriptomics confirm osteogenic and chondrogenic genes are upregulated in their respective microgel regions. These studies highlight the tunable and functionalizable nature of microgels and the importance of macroporous void space. [ABSTRACT FROM AUTHOR]

The ability to precisely arrange and control the assembly of diverse cell types into intricate 3D structures remains a critical challenge in tissue engineering. Herein, a versatile and programmable 3D cell sheet assembly is described technology by developing a biodegradable nanochannel (BNC) membrane to fulfill this unmet need. This membrane, hierarchically assembled from 2D nanomaterial aggregates, exhibits both exceptional fluid permeability and rapid biodegradation under physiological conditions. The unique properties of the BNC membrane enable precise spatial and temporal control over cell assembly, facilitating the creation of complex 3D cellular architectures. The BNC membrane is integrated with a programmable negative‐pressure‐based cell assembly strategy to form single and multicellular 3D sheets in a highly controllable manner. To demonstrate the feasibility and translatability of this technology in the field of tissue engineering approaches to screen stem cell‐derived therapeutics with “core–shell” macrophage‐fibroblast multicellular patterns and treat murine diabetic skin wounds via scaffold‐free 3D adipose‐derived mesenchymal stem cell (ADMSC) sheets are devised. In summary, the results demonstrate that the BNC membrane‐based 3D cell sheet assembly approach significantly advances current tissue engineering capabilities, offering substantial potential for both regenerative medicine applications and the development of physiologically relevant disease models. [ABSTRACT FROM AUTHOR]

Liver cancer, characterized as a kind of malignant tumor within the digestive system, poses great health harm, and immune escape stands out as an important reason for its occurrence and development. Chemokines, pivotal in guiding immune cells' migration, is necessary to initiate and deliver an effective anti-tumor immune response. Therefore, understanding the chemotactic environment and identifying chemokines that regulate recruitment of immune cells to the tumor microenvironment (TME) are critical to improve current immunotherapy interventions. Herein, we report a well-defined inverse opal scaffold generated with a microfluidic emulsion template for the construction of a vascularized liver tumor model, offering insights into immune cells' recruitment. Due to the excellent 3D porous morphology of the inverse opal scaffold, human hepatocellular carcinoma cells can aggregate in the pores of the scaffold to form uniform multicellular tumor spheroids. More attractively, the vascularized liver tumor model can be achieved by constructing a 3D co-culture system involving endothelial cells and hepatocellular carcinoma cells. The results demonstrate that the 3D co-cultured tumor cells increase the neutrophil chemokines remarkably and recruit neutrophils to tumor tissues, then promote tumor progression. This approach opens a feasible avenue for realizing a vascularized liver tumor model with a reliable immune microenvironment close to that of a solid tumor of liver cancer. [ABSTRACT FROM AUTHOR]

Skin injuries are common problems and large skin defects or infected skin needs extra attention that make the researchers find new solutions. Herein, a novel biocompatible, biodegradable antibacterial scaffold containing gelatin, TiO2, polycaprolactone, and silk fibroin loaded with different ratios of curcumin (0.5, 1, and 1.5% wt.) was fabricated with electrospinning technique and was tested with various in vitro tests. The cellular investigations (cell adhesion, cell viability, and in vitro migration test) and antibacterial assay revealed the higher efficiency of the scaffold with 1% wt. curcumin and further investigation were performed on this scaffold. The morphological observation confirmed the nanofibrous structure of the scaffold, with 0.10 ± 0.015 μm average fiber diameter. This scaffold showed hydrophilic nature with high swelling ratio absorption and 76.45 ± 5.19% degradation ratio after 2 weeks. Also, it could provide adequate mechanical properties for skin regeneration. The drug-releasing investigation revealed Cur's controlled release over 48 h. Therefore, this biocompatible and antibacterial scaffold showed high potential for treating skin injuries and is suggested for future in vivo studies. [ABSTRACT FROM AUTHOR]

Hydrogel skin grafts provide a moist environment and act as a regenerative template to the newly formed tissue. In this study, we developed 3D-bio-printed hydrogels using methacrylated pectin and methacrylated gelatin together with an antibacterial agent (curcumin), a bioactive agent (Vitamin-C) and fibroblast cells. Curcumin release was almost 10 times higher at pH 7.4 than pH 5.0, and it demonstrated antimicrobial affinity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The developed 3D-bio-printed hydrogels containing cells and bioactive agents demonstrated high cell viability, cell proliferation, and collagen production, and are promising skin graft candidates for the treatment of full-thickness problematic wounds. [ABSTRACT FROM AUTHOR]

Articular cartilage regeneration is a challenge in tissue engineering. Although diverse materials have been developed for this purpose, cartilage regeneration remains suboptimal. The integration of nanomaterials into 3D network materials holds great potential in the improvement of key mechanical properties, particularly important for osteochondral replacement scaffolds and even to function as carriers for disease‐modifying drugs or other regulatory signals. In this study, a simple yet effective cell‐free nanoenabled Col‐PLA scaffold specially designed to enhance cartilage regeneration and modulate inflammatory response is proposed, by incorporating poly(lactic‐co‐glycolic acid) (PLGA) ibuprofen nanoparticles (NPs) into a collagen/polylactide (Col‐PLA) matrix. The developed nanoenabled scaffold successfully decreases IL‐1β release and leads to primary human chondrocytes survival, ultimately restoring extracellular matrix (ECM) production under inflammatory conditions. The nanoenabled Col‐PLA scaffolds secretome effectively decreases macrophage invasion in vitro, as well as neutrophil infiltration and inflammatory mediators', namely the complement component C5/C5a, C‐reactive protein, IL‐1β, MMP9, CCL20, and CXCL1/KC production in vivo in a rodent air‐pouch model. Overall, the established nanoenabled scaffold has the potential to support chondrogenesis as well as modulate inflammatory response, overcoming the limitations of traditional tissue engineering strategies. [ABSTRACT FROM AUTHOR]

Silk fibroin hydrogels are extensively explored for tissue engineering and regenerative medicine as an artificial extracellular matrix (ECM) that can support tissue growth. However, the nanometer pore size of hydrogels limits adequate cell, tissue, and vascular infiltration. Microgel scaffolds are an emerging class of microporous biomaterials formed by annealing small microscale hydrogels (microgels) into a 3D construct. In this work, silk microgels are generated using a microfluidic device that allows tuning of the microgel diameter (100–400 µm) and are stabilized via visible light‐initiated photo‐crosslinking of native tyrosine residues in silk. Microgels are then covalently annealed using silk solution as glue and the same cytocompatible visible light‐initiated crosslinking to form microgel scaffolds. Unlike the nano‐porosity of bulk photo‐crosslinked silk hydrogels, the microgel scaffolds have an average pore diameter of 29 ± 17 or 192 ± 81 µm depending on the microgel size, with enhanced mechanical properties compared to bulk hydrogels. This microporosity supports enhanced cell spreading and proliferation in vitro and increases scaffold remodeling in vivo, encouraging improved tissue infiltration and matrix deposition. The microgel size and material format also affect inflammatory responses in vivo. This work demonstrates that silk microgels and microgel scaffolds are promising candidates for tissue engineering and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

In recent years, people have had more expectations from the developed technology in medicine, especially in the field of orthopedics and traumatology. Tissue engineers are interested in techniques that benefit from patients' cells and biomaterials, instead of prostheses and implants. On the other hand, researchers have begun to use various medicinal plants for regeneration and anti-cancer studies. In the present study, we aimed to produce cartilage and bone inductive scaffolds for osteochondral tissue engineering applications with the addition of hawthorn or elderberry extracts. Firstly, wet electro-spun poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) fibers were integrated with a loofah mat. Then, they were impregnated into chitosan solution with/without hawthorn or elderberry extract. Composite hydrogel scaffolds were obtained by cross-linking with 0.3% (w/v) genipin. Fabricated scaffolds had more than 90% porosity and showed swelling capacity in the range of 1500–2200%. Based on the in vitro biocompatibility analyses using mesenchymal stem cells (MSCs), all the fabricated scaffolds were found to be biocompatible by WST-1, ALP activity, and GAG content analysis. Also, histological/immunohistochemical analyses showed that hawthorn and elderberry extract addition increased MSCs proliferation and collagen type I and II positivity. Consequently, all the scaffolds showed promising features for osteochondral tissue engineering applications. [ABSTRACT FROM AUTHOR]

Decellularization of plant tissues is an emerging route to fabricate scaffolds for tissue engineering and regenerative medicine. Although significant progress has been made in the field of plant tissue decellularization, functionalization of plant scaffolds is still an emerging field, and loading them with L-ascorbic acid to promote skin regeneration has not yet been reported. L-ascorbic acid is an antioxidant that plays a key role in collagen synthesis as a cofactor of lysyl hydroxylase and prolyl hydroxylase. It has been shown to have significant importance in physiological wound healing by stimulating fibroblasts to produce collagen at both the molecular and the genetic levels. In this work, we aimed to fabricate an ascorbic acid-releasing bioactive scaffold by introducing a stable form of ascorbic acid, L-ascorbic acid 2-phosphate (AA2P), into decellularized baby spinach leaves and investigated its biological activity in vitro. Our results demonstrated that AA2P could be easily introduced into decellularized baby spinach leaf scaffolds and subsequently released within the effective dose range. AA2P-releasing baby spinach leaves were found to increase metabolic activity and enhance collagen synthesis in L929 fibroblasts after 21 days. In conclusion, this study demonstrated the fabrication of a novel functionalized skin tissue engineering scaffold and made a significant contribution to the fields of plant decellularization and skin tissue engineering. [ABSTRACT FROM AUTHOR]

Advanced therapeutic dressings are the current research interest that achieves rapid and complete wound healing. The healing of skin wounds demonstrates a remarkable cellular function process that is distinct in nature and involves the interaction of various cells, growth factors, and cytokines. In this study, nanofibrous scaffolds were prepared using poly(ε-caprolactone) and polylactic acid as mat scaffolds. Also, copper nanoparticles (CuNPs) and curcumin were added to fabricate a hybrid nanocomposite scaffold using the electrospinning technique. The fabricated scaffolds were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), tensile analysis, porosity, and water vapor transmission rate. SEM analysis proved the nanostructured fibers have suitable porosity without any beads. The presence of CuNPs in the PCL-Cu nanofibrous mat was confirmed by TEM analysis. The tensile test confirmed an increase and decrease in the elongation ratio by CuNPs and curcumin addition, respectively. The biocompatibility and cell attachment to the nanofibers were proved by MTT and DAPI staining which proved a significantly positive effect of curcumin in the cell growth. The scaffold can hinder both the gram-negative and gram-positive bacteria through direct contact with them. This research study showed that the addition of CuNPs and curcumin in the hybrid nanocomposite scaffold compensates for each other's shortcomings and has the potential to be used in wound healing applications. [ABSTRACT FROM AUTHOR]

Tissue engineering applications in bone defect treatment have shown promising outcomes over the past decade. In this context, taking advantage of bioactive scaffolds mimicking the intrinsic composition of bone has resulted in remarkable effects on bone regeneration. In this study, Zirconium-based metal-organic framework, known as MOF 801, was synthesized and incorporated into the gelatin matrix as an osteoconductive agent to fabricate a nanocomposite bone scaffold by freeze-drying method. Physical and chemical characteristics of MOF 801 and nanocomposite scaffolds were analyzed using FE-SEM, EDS, XRD, ICP and FTIR. Besides, the biological activity of the prepared scaffolds was evaluated by MTT, alizarin red staining, crystal violet staining, and ALP assays. Inclusion of MOF 801 NPs into the scaffolds resulted in enhancement of their compressive strength up to 15 ± 0.05 MPa. The nanocomposite samples containing MOF 801 NPs also exhibited favorable bioactive feature that was confirmed by their apatite-forming ability on their surfaces upon immersion in SBF solution. The Zr ion and fumarate release studies illustrated sustained release profiles from the gelatin matrix, leading to both antioxidant and anti-inflammatory properties. MTT assay results affirmed biocompatibility of scaffolds containing up to 5 % w/w MOF 801, besides the crystal violet assay exhibited proper cell confluency and adhesion. Eventually, Alizarin red and ALP activity assays revealed that an increment of MOF 801 could induce calcium mineralization and Alkaline Phosphatase enzyme production in MG-63 cells confirming the potential of prepared scaffolds for related bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Self-assembling peptide-based hydrogels have become a highly attractive scaffold for three-dimensional (3D) in vitro disease modeling as they provide a way to create tunable matrices that can resemble the extracellular matrix (ECM) of various microenvironments. Alzheimer's disease (AD) is an exceptionally complex neurodegenerative condition; however, our understanding has advanced due to the transition from two-dimensional (2D) to 3D in vitro modeling. Nonetheless, there is a current gap in knowledge regarding the role of amyloid structures, and previously developed models found long-term difficulty in creating an appropriate model involving the ECM and amyloid aggregates. In this report, we propose a multi-component self-assembling peptide-based hydrogel scaffold to mimic the amyloid-beta (β) containing microenvironment. Characterization of the amyloid-β-mimicking hydrogel (Col-HAMA-FF) reveals the formation of β-sheet structures as a result of the self-assembling properties of phenylalanine (Phe, F) through π−π stacking of the residues, thus mimicking the amyloid-β protein nanostructures. We investigated the effect of the amyloid-β-mimicking microenvironment on healthy neuronal progenitor cells (NPCs) compared to a natural-mimicking matrix (Col-HAMA). Our results demonstrated higher levels of neuroinflammation and apoptosis markers when NPCs were cultured in the amyloid-like matrix compared to a natural brain matrix. Here, we provided insights into the impact of amyloid-like structures on NPC phenotypes and behaviors. This foundational work, before progressing to more complex plaque models, provides a promising scaffold for future investigations on AD mechanisms and drug testing. In this study, we engineered two multi-component hydrogels: one to mimic the natural extracellular matrix (ECM) of the brain and one to resemble an amyloid-like microenvironment using a self-assembling peptide hydrogel. The self-assembling peptide mimics β-amyloid fibrils seen in amyloid-β protein aggregates. We report on the culture of neuronal progenitor cells within the amyloid-mimicking ECM scaffold to study the impact through marker expressions related to inflammation and DNA damage. This foundational work, before progressing to more complex plaque models, offers a promising scaffold for future investigations on AD mechanisms and drug testing. [Display omitted] [ABSTRACT FROM AUTHOR]

Advancements in new treatment methods are becoming increasingly necessary due to a longer life expectancy, particularly in the field of osteochondral tissue engineering. In the present study, osteochondral tissue scaffolds with/without the addition of hawthorn or elderberry extracts were fabricated. Poly(ethylene glycol) diglycidyl ether (PEGDE) cross‐linked carboxymethyl chitosan hydrogel scaffold matrix was used as a control group. The addition of the plant extracts resulted in open porous structures with pore sizes around 100–450 μm and elastic modulus between 0.5 and 0.7 MPa, biomimicking the osteochondral tissue. Scaffolds containing either plant extract showed a high swelling tendency (1500–1750%) and a delayed release of the extracts after a week. Furthermore, the weight loss of the scaffolds after an enzymatic degradation for 56 days was ~30%. In addition, in vitro biocompatibility analyses were performed using bone marrow‐derived mesenchymal stem cells confirming non‐cytotoxicity for all the scaffold types. Biochemical assessment of alkaline phosphatase activity and glycosaminoglycan content yielded results consistent with osteochondral scaffold requirements. Finally, immunohistochemical analyses indicated that the plant extract addition, especially elderberry, increased collagen type I and type II formation. As a result, the addition of both hawthorn and elderberry extracts is a promising approach to osteochondral tissue regeneration. [ABSTRACT FROM AUTHOR]

Scaffolds play a key role in cultured meat production by providing an optimal environment for efficient cell attachment, growth, and development. This study investigated the effects of gelatin coating on the adhesion, proliferation, and adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) cultured on soy protein–agarose scaffolds. Gelatin-coated scaffolds were prepared using 0.5% and 1.0% (w/v) gelatin solutions. The microstructure, water absorption rate, mechanical strength, cytotoxicity, cell adhesion, proliferation, and differentiation capabilities of the scaffolds were analyzed. Field emission scanning electron microscopy revealed the porous microstructure of the scaffolds, which was suitable for cell growth. Gelatin-coated scaffolds exhibited a significantly higher water absorption rate than that of non-coated scaffolds, indicating increased hydrophilicity. In addition, gelatin coating increased the mechanical strength of the scaffolds. Gelatin coating did not show cytotoxicity but significantly enhanced cell adhesion and proliferation. The gene expression levels of peroxisome proliferator-activated receptor gamma, CCAT/enhancer-binding protein alpha, and fatty acid-binding protein 4 were upregulated, and lipid accumulation was increased by gelatin coating. These findings suggest that gelatin-coated scaffolds provide a supportive microenvironment for ADSC growth and differentiation, highlighting their potential as a strategy for the improvement of cultured meat production and adipose tissue engineering. [ABSTRACT FROM AUTHOR]

Tendon injuries are common orthopedic ailments with a challenging healing trajectory, especially in cases like the Achilles tendon afflictions. The healing trajectory of tendon injuries is often suboptimal, leading to scar formation and functional impairment due to the inherent low metabolic activity and vascularization of tendon tissue. As pressing is needed for effective interventions, efforts are made to explore biomaterials to augment tendon healing. However, tissue engineering approaches face hurdles in optimizing tissue scaffolds and nanomedical strategies. To navigate these challenges, an injectable hydrogel amalgamated with human umbilical vein endothelial cells-derived exosomes (HUVECs-Exos) was prepared and named H-Exos-gel in this study, aiming to enhance tendon repair. In our research involving a model of Achilles tendon injuries in 60 rats, we investigated the efficacy of H-Exos-gel through histological assessments performed at 2 and 4 weeks and behavioral assessments conducted at the 4-week mark revealed its ability to enhance the Achilles tendon's mechanical strength, regulate inflammation and facilitate tendon regeneration and functional recovery. Mechanically, the H-Exos-gel modulated the cellular behaviors of macrophages and tendon-derived stem cells (TDSCs) by inhibiting inflammation-related pathways and promoting proliferation-related pathways. Our findings delineate that the H-Exos-gel epitomizes a viable bioactive medium for tendon healing, heralding a promising avenue for the clinical amelioration of tendon injuries. [ABSTRACT FROM AUTHOR]

As a 3D rapid prototyping technology, 3D printing (3DP) technology has been widely applied in medical research, fabricating various medical devices or implants. With the development of biomaterials and cell‐related technologies, 3DP, especially bioprinting technology, is quietly bringing great changes and opportunities in the medical industry. Beyond surgical models, medical devices, and implants, traditional 3DP, cell‐based 3D bioprinting, and emerging 4D printing (4DP) have significantly aided in the advancement and manufacture of pharmaceuticals and biological alternatives for tissue engineering. It is envisioned that future healthcare systems, based on evolving 3DP technology and precision medicine, will deliver customized solutions that cater to the unique differences and needs of each patient. In this review work, several mainstream 3D bioprinting technologies are presented, with a focus on recent advances in 3DP for pharmaceutical engineering and important tissue engineering, including vascular and bone tissue engineering. Challenges and future prospects of 3DP for drug discovery, drug delivery systems, artificial blood vessels, vascular and bone tissue engineering scaffolds, and practical applications are also covered. Finally, the differences between 3DP and 4DP, as well as the advantages and disadvantages of different stimulus response mechanisms in 4DP and their potential applications are summarized. [ABSTRACT FROM AUTHOR]

In this study, hydroxyapatite (HAp)/mineralized collagen hydrogel composites were prepared by incorporating different amounts of dopamine‐modified HAp particles during the process of collagen self‐assembly and simultaneous mineralization. Zeta potential results showed that the surface charge of modified HAp particles was altered, and scanning electron microscopy patterns indicated that HAp particles were uniformly distributed in the hydrogels. The occurrence of collagen biomineralization was indirectly reflected by the results of Ca and P content in the hydrogel supernatant, and the results of ash content indicated that the mineral content of the hydrogels could be up to 60% or more, which was close to the inorganic content in natural bone. The results of CCK‐8 and ALP activity assays showed that mineralized collagen hydrogels were favorable for cell proliferation and differentiation, and the hydrogels containing dopamine‐modified HAp particles obtained a higher expression of osteogenic differentiation related transcription factor. The results showed that the excellent adhesion properties of dopamine contributed to enhance the bone repair potential of the composites, suggesting that mineralized collagen hydrogel composites containing dopamine‐modified HAp particles, which could mimic the structure and composition of bone, have a promising potential as bone tissue engineering scaffolds. [ABSTRACT FROM AUTHOR]

Adipose tissues, particularly beige and brown adipose tissue, play crucial roles in energy metabolism. Brown adipose tissues' thermogenic capacity and the appearance of beige cells within white adipose tissue have spurred interest in their metabolic impact and therapeutic potential. Brown and beige fat cells, activated by environmental factors like cold exposure or by pharmacology, share metabolic mechanisms that drive non-shivering thermogenesis. Understanding these two cell types requires advanced, yet broadly applicable in vitro models that reflect the complex microenvironment and vasculature of adipose tissues. Here we present mouse vascularized adipose spheroids of the stromal vascular microenvironment from inguinal white adipose tissue, a tissue with 'beiging' capacity in mice and humans. We show that adding a scaffold improves vascular sprouting, enhances spheroid growth, and upregulates adipogenic markers, thus reflecting increased adipocyte maturity. Transcriptional profiling via RNA sequencing revealed distinct metabolic pathways upregulated in our vascularized adipose spheroids, with increased expression of genes involved in glucose metabolism, lipid metabolism, and thermogenesis. Functional assessment demonstrated increased oxygen consumption in vascularized adipose spheroids compared to classical 2D cultures, which was enhanced by β-adrenergic receptor stimulation correlating with elevated b-adrenergic receptor expression. Moreover, stimulation with the naturally occurring adipokine, FGF21, induced Ucp1 mRNA expression in the vascularized adipose spheroids. In conclusion, vascularized inguinal white adipose tissue spheroids provide a physiologically relevant platform to study how the stromal vascular microenvironment shapes adipocyte responses and influence activated thermogenesis in beige adipocytes. [ABSTRACT FROM AUTHOR]

Previously, we reported successful cellular expansion of a murine colorectal carcinoma cell line (CT-26) using a three-dimensional (3D) engineered extracellular matrix (EECM) fibrillar scaffold structure. CCL-247 were grown over a limited time period of 8 days on 3D EECM or tissue culture polystyrene (TCPS). Cells were then assayed for growth, electroporation efficiency and Vigil manufacturing release criteria. Using EECM scaffolds, we report an expansion of CCL-247 (HCT116), a colorectal carcinoma cell line, from a starting concentration of 2.45 × 105 cells to 1.9 × 106 cells per scaffold. Following expansion, 3D EECM-derived cells were assessed based on clinical release criteria of the Vigil manufacturing process utilized for Phase IIb trial operation with the FDA. 3D EECM-derived cells passed all Vigil manufacturing release criteria including cytokine expression. Here, we demonstrate successful Vigil product manufacture achieving the specifications necessary for the clinical trial product release of Vigil treatment. Our results confirm that 3D EECM can be utilized for the expansion of human cancer cell CCL-247, justifying further clinical development involving human tissue sample manufacturing including core needle biopsy and minimal ascites samples. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function. [ABSTRACT FROM AUTHOR]

The hydrophobic nature of synthetic polymers poses a substantial barrier since it limits cell-seeding and proliferation scaffold performance. To overcome this challenge, the present research attempts to employ in-situ UV electrospinning and plasma surface modification techniques to fabricate a three-dimensional PAN/PVA-gelatin scaffold. The proposed scaffold holds great potential in mitigating hydrophobicity limitations, thereby facilitating enhanced cell adhesion and proliferation. The SEM results indicated that exposure to UV irradiation resulted in the formation of wavy shapes in the PAN microstructures and crosslinking between fibers within the scaffold. Moreover, plasma treatment induced the formation of pores on the PAN surface, with an average diameter of 43 µm, corresponding to the size range of mouse fibroblast cells. Furthermore, the plasma treatment provided roughness augmentation of the scaffold surface, which played a crucial role in enhancing cell adhesion and elongation on the modified scaffold surface. Comparatively, the plasma-modified scaffolds exhibited a higher proportion of viable cells than the unmodified scaffolds (p < 0.05). Moreover, the implementation of perforations in the PAN layer via plasma treatment reduced the number of necrosis cells in comparison to the other samples. In contrast, the unmodified scaffold showed a higher percentage of apoptosis cells (p < 0.05). [ABSTRACT FROM AUTHOR]

Pharmaceutical formulations, polymer-based nanofibers, which have higher surface area per unit mass of solid, enable and contribute to functions linked to surface shape. Nanofibers can be made using a number of different methods, but only electrospinning technology has been specifically focused on producing a wide variety of these common polymer-based nanofibers. The manufacturing potential of just this method is enormous. Electrospinning is also the most versatile, as it can produce a wide range of nanowire assemblies that, with the right tweaks, might improve the performance of goods made from Nanofibers. For these reasons, it is crucial and necessary to study the many factors and procedures that go into making the best possible nanofibers. Standard processes and tools may be used to examine nanofibers' structure, morphology, and geometry, as well as their tensile and elongation characteristics. In this article, we take a look at the various ways in which polymer composite nanofibers can be used in tissue engineering, such as in tissue scaffolds and cutting-edge wound dressings for chronic wound therapy, in addition to their potential roles in drug delivery systems, in clothing protectors, and sensors. There are just a select few of these products that have been released so far, but more nano- and bio-sciences products are expected to hit the market shortly. Polymer-based nanofibers have emerged as a result of efforts to commercialize these applications. A variety of fields, including biology, nutrition, bioengineering, pharmaceuticals, and healthcare, find this structured fiber useful. [ABSTRACT FROM AUTHOR]

Understanding how porous biomaterials interact with cells at their surface and how they either promote or inhibit cellular processes has presented several challenges. Additive manufacturing enables the fabrication of scaffolds with distinct compositions and designs for different tissue engineering applications. To evaluate the in vitro performance of multiple printed materials, biochemical assays can be limiting in providing valuable insight and key information to select the best tissue destination. Omics technologies like proteomics are crucial for studying important cellular events and gathering valuable information about cellular processes and mechanisms. However, only few studies focus on proteomics to decipher cell–material interactions and cell differentiation on additive manufactured scaffolds. Here, scaffolds were fabricated using three polymers (polycaprolactone (PCL), poly(ethylene oxide)–poly(butylene terephthalate) (PEOT/PBT), and polylactic acid (PLA)) through additive manufacturing. Their chondrogenic and osteogenic potential were characterized and compared using human bone marrow‐derived mesenchymal stem cells (hBMSCs) through proteomics analysis. The 3D scaffolds were all hydrophilic and displayed Young's moduli close to those of bone or cartilage for PLA and PCL and PEOT/PBT, respectively. Biochemical assays indicated that PEOT/PBT and PLA scaffolds have a greater chondrogenic potential by higher glycosaminoglycan (GAG) and collagen deposition compared to PCL. PLA and PEOT/PBT showed to be more effective in promoting bone formation, as evidenced by higher calcium deposits detected by alizarin red staining, and higher alkaline phosphatase (ALP), especially for PLA in osteogenic medium. Proteomics data revealed the most distinct separation between conditions in chondrogenic medium, which had the highest protein identification rates. Pathway analysis showed that PCL did not induce any differentiation‐related pathways when compared to PEOT/PBT and PLA in any of the tested media conditions. Analysis of PEOT/PBT proteins showed pathways involved in chondrogenesis in all three media and pathways related to hypertrophic phenotype progression in chondrogenic medium. These data suggests that PEOT/PBT is a valuable candidate for cartilage and osteochondral applications, able to drive hBMSCs differentiation without the need of growth factors. PLA was also a valuable candidate for cartilage and bone applications by upregulating both chondrogenic and osteogenic‐related proteins in maintenance and chondrogenic media. In osteogenic and maintenance media, the upregulation of angiogenic proteins makes PLA a better candidate for bone application where vascularization is key. [ABSTRACT FROM AUTHOR]

Due to the good extracellular matrix biomimetic properties, silk fibroin (SF) hydrogels have been extensively concerned and studied in the fields of tissue engineering scaffold and 3D cell culture. The most widely used ones among them are mild chemical crosslinked SF hydrogels. However, as the inevitable movement and self-assembly of hydrophobic segments of silk fibroin in such hydrogels, the conformation of silk fibroin transforms from random coil to the β-sheet conformation with lower energy level, which will dynamically change the basic characteristics (such as the stiffness and pore size) of the hydrogels. Consequently, unknown and non-negligible impacts on the biomedical application of the hydrogel were induced. Based on this perspective, the SF hydrogel, which was crosslinked by horseradish peroxidase in a mild manner, was chosen as model materials. The strategy of changing related crosslinking density was used to successfully regulate the rate of protein conformational transition in SF hydrogels. At the same time, the effect of protein conformational transition rate in such an SF hydrogel on the proliferation of cells adhering to its surface was investigated. Results showed that the rate of protein conformational transition in corresponding hydrogels was inversely related to the crosslinking density. The lower the crosslinking density was, the faster the conformational transition was. Meanwhile, the proliferation of mouse embryonic fibroblasts (NIH3T3) cells on the hydrogel surface was generally positively correlated with the rate of protein conformational transition in corresponding hydrogels. However, as it also existed the effects of the accompanied initial crosslinking densities, the final trend was that the total number of cells on hydrogels with medium conformational transition rate was relatively low, and that on hydrogels with the fastest conformational transition rate was relatively high. [ABSTRACT FROM AUTHOR]

In animals with germ plasm, embryonic germline precursors inherit germ granules, condensates proposed to regulate mRNAs coding for germ cell fate determinants. In Caenorhabditis elegans, mRNAs are recruited to germ granules by MEG-3, a sequence non-specific RNAbinding protein that forms stabilizing interfacial clusters on germ granules. Using fluorescence in situ hybridization, we confirmed that 441 MEG-3-bound transcripts are distributed in a pattern consistent with enrichment in germ granules. Thirteen are related to transcripts reported in germ granules in Drosophila or Nasonia. The majority, however, are low-translation maternal transcripts required for embryogenesis that are not maintained preferentially in the nascent germline. Granule enrichment raises the concentration of certain transcripts in germ plasm but is not essential to regulate mRNA translation or stability. Our findings suggest that only a minority of germ granule-associated transcripts contribute to germ cell fate in C. elegans and that the vast majority function as non-specific scaffolds for MEG-3. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) structures are actually the state-of-the-art technique to create porous scaffolds for tissue engineering. Since regeneration in cartilage tissue is limited due to intrinsic cellular properties this study aims to develop and characterize three-dimensional porous scaffolds of poly (L-co-D, L lactide-co-trimethylene carbonate), PLDLA-TMC, obtained by 3D fiber deposition technique. The PLDLA-TMC terpolymer scaffolds (70:30), were obtained and characterized by scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, thermal gravimetric analysis, compression mechanical testing and study on in vitro degradation, which showed its amorphous characteristics, cylindrical geometry, and interconnected pores. The in vitro degradation study showed significant loss of mechanical properties compatible with a decrease in molar mass, accompanied by changes in morphology. The histocompatibility association of mesenchymal stem cells from rabbit's bone marrow, and PLDLA-TMC scaffolds, were evaluated in the meniscus regeneration, proving the potential of cell culture at in vivo tissue regeneration. Nine New Zealand rabbits underwent total medial meniscectomy, yielding three treatments: implantation of the seeded PLDLA-TMC scaffold, implantation of the unseeded PLDLA-TMC and negative control (defect without any implant). After 24 weeks, the results revealed the presence of fibrocartilage in the animals treated with polymer. However, the regeneration obtained with the seeded PLDLA-TMC scaffolds with mesenchymal stem cells had become intimal to mature fibrocartilaginous tissue of normal meniscus both macroscopically and histologically. This study demonstrated the effectiveness of the PLDLA-TMC scaffold in meniscus regeneration and the potential of mesenchymal stem cells in tissue engineering, without the use of growth factors. It is concluded that bioresorbable polymers represent a promising alternative for tissue regeneration. [ABSTRACT FROM AUTHOR]

Tissue engineering aims at producing in the laboratory new biological tissues by combining cells, scaffold materials, and biochemistry. Recent successes in the field are promising, but sustainability and reproducibility issues still limit the large-scale applications of this technique. The present work addresses the development of a computational model that describes cell motility in biodegradable hydrogel scaffolds. The goal is to support the understanding and the control of the first stage of tissue formation, when cells seeded into the scaffold congregate to form clusters, necessary precursors of tissue blocks. Cellular migration is treated as an advective/diffusive process modeled via the phase-field approach. The chemo-biological mechanisms incorporated in the modeling framework are: (i) the natural degradation of the hydrogel; (ii) chemotaxis induced by cell-cell signaling pathways; (iii) nutrient diffusion through the construct and its consumption by cells. Each cell initially moves following a random path, subsequently switching to a directed chemically-driven motion when the presence of other cells is sensed in its neighborhood. Numerical results highlight the role of the interplay between nutrient availability in the construct, chemoattractant production, scaffold degradation and cell motility, showing that the proposed model could pave the way towards efficient computationally-aided tools for the optimization of neotissue mass production. [ABSTRACT FROM AUTHOR]

Aerogels are lightweight and highly porous materials that have been found to have great potential in biomedical research because of some of their unique properties, such as their high surface area, tunable porosity, and biocompatibility. Researchers have been exploring ways to use aerogels to create biomimetic scaffolds inspired by natural extracellular matrices (ECMs) for various biomedical applications. Aerogel scaffolds can serve as three-dimensional (3D) templates for cell growth and tissue regeneration, promoting wound healing and tissue repair. Additionally, aerogel-based scaffolds have great potential in controlled drug delivery systems, where their high surface area and porosity enable the efficient loading and release of therapeutic agents. In this review, we discuss biopolymer-based biomimetic aerogel scaffolds for tissue engineering, drug delivery, and biosensors. Finally, we also discuss the potential directions in the development of aerogel-based biomimetic scaffolds. [ABSTRACT FROM AUTHOR]

Ti6Al4V superalloy is recognized as a good candidate for bone implants owing to its biocompatibility, corrosion resistance, and high strength-to-weight ratio. While dense metal implants are associated with stress shielding issues due to the difference in densities, stiffness, and modulus of elasticity compared to bone tissues, the surface of the implant/scaffold should mimic the properties of the bone of interest to assure a good integration with a strong interface. In this study, we investigated the additive manufacturing of porous Ti6Al4V scaffolds and coating modification for enhanced osteoconduction using osteoblast cells. The results showed the successful fabrication of porous Ti6Al4V scaffolds with adequate strength. Additionally, the surface treatment with NaOH and Dopamine Hydrochloride (DOPA) promoted the formation of Dopamine Hydrochloride (DOPA) coating with an optimized coating process, providing an environment that supports higher cell viability and growth compared to the uncoated Ti6Al4V scaffolds, as demonstrated by the higher proliferation ratios observed from day 1 to day 29. These findings bring valuable insights into the surface modification of 3D-printed scaffolds for improved osteoconduction through the coating process in solutions. [ABSTRACT FROM AUTHOR]

The aim of this study is to provide an overview of the current state-of-the-art in the fabrication of bioceramic scaffolds for bone tissue engineering, with an emphasis on the use of three-dimensional (3D) technologies coupled with generative design principles. The field of modern medicine has witnessed remarkable advancements and continuous innovation in recent decades, driven by a relentless desire to improve patient outcomes and quality of life. Central to this progress is the field of tissue engineering, which holds immense promise for regenerative medicine applications. Scaffolds are integral to tissue engineering and serve as 3D frameworks that support cell attachment, proliferation, and differentiation. A wide array of materials has been explored for the fabrication of scaffolds, including bioceramics (i.e., hydroxyapatite, beta-tricalcium phosphate, bioglasses) and bioceramic–polymer composites, each offering unique properties and functionalities tailored to specific applications. Several fabrication methods, such as thermal-induced phase separation, electrospinning, freeze-drying, gas foaming, particle leaching/solvent casting, fused deposition modeling, 3D printing, stereolithography and selective laser sintering, will be introduced and thoroughly analyzed and discussed from the point of view of their unique characteristics, which have proven invaluable for obtaining bioceramic scaffolds. Moreover, by highlighting the important role of generative design in scaffold optimization, this review seeks to pave the way for the development of innovative strategies and personalized solutions to address significant gaps in the current literature, mainly related to complex bone defects in bone tissue engineering. [ABSTRACT FROM AUTHOR]

The umbilical cord is a material that enhances regeneration and is devoid of age-related changes in the extracellular matrix (ECM). The aim of this work was to develop a biodegradable scaffold from a decellularized human umbilical cord (UC-scaffold) to heal full-thickness wounds. Decellularization was performed with 0.05% sodium dodecyl sulfate solution. The UC-scaffold was studied using morphological analysis methods. The composition of the UC-scaffold was studied using immunoblotting and Fourier transform infrared spectroscopy. The adhesion and proliferation of mesenchymal stromal cells were investigated using the LIVE/DEAD assay. The local reaction was determined by subcutaneous implantation in mice (n = 60). A model of a full-thickness skin wound in mice (n = 64) was used to assess the biological activity of the UC-scaffold. The proposed decellularization method showed its effectiveness in the umbilical cord, as it removed cells and retained a porous structure, type I and type IV collagen, TGF-β3, VEGF, and fibronectin in the ECM. The biodegradation of the UC-scaffold in the presence of collagenase, its stability during incubation in hyaluronidase solution, and its ability to swell by 1617 ± 120% were demonstrated. Subcutaneous scaffold implantation in mice showed gradual resorption of the product in vivo without the formation of a dense connective tissue capsule. Epithelialization of the wound occurred completely in contrast to the controls. All of these data suggest a potential for the use of the UC-scaffold. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases remain a leading cause of mortality globally, with atherosclerosis representing a significant pathological means, often leading to myocardial infarction. Coronary artery bypass surgery, a common procedure used to treat coronary artery disease, presents challenges due to the limited autologous tissue availability or the shortcomings of synthetic grafts. Consequently, there is a growing interest in tissue engineering approaches to develop vascular substitutes. This review offers an updated picture of the state of the art in vascular tissue engineering, emphasising the design of scaffolds and dynamic culture conditions following a biomimetic approach. By emulating native vessel properties and, in particular, by mimicking the three-layer structure of the vascular wall, tissue-engineered grafts can improve long-term patency and clinical outcomes. Furthermore, ongoing research focuses on enhancing biomimicry through innovative scaffold materials, surface functionalisation strategies, and the use of bioreactors mimicking the physiological microenvironment. Through a multidisciplinary lens, this review provides insight into the latest advancements and future directions of vascular tissue engineering, with particular reference to employing biomimicry to create systems capable of reproducing the structure–function relationships present in the arterial wall. Despite the existence of a gap between benchtop innovation and clinical translation, it appears that the biomimetic technologies developed to date demonstrate promising results in preventing vascular occlusion due to blood clotting under laboratory conditions and in preclinical studies. Therefore, a multifaceted biomimetic approach could represent a winning strategy to ensure the translation of vascular tissue engineering into clinical practice. [ABSTRACT FROM AUTHOR]

Ice‐templated porous biomaterials possess transformative potential in regenerative medicine; yet, scaling up ice‐templating processes for broader applications—owing to inconsistent pore formation—remains challenging. This study reports an innovative semi‐solid freeze‐casting technique that draws inspiration from semi‐solid metal processing (SSMP) combined with ice cream‐production routines. This versatile approach allows for the large‐scale assembly of various materials, from polymers to inorganic particles, into isotropic 3D scaffolds featuring uniformly equiaxed pores throughout the centimeter scale. Through (cryo‐)electron microscopy, X‐ray tomography, and finite element modeling, the structural evolution of ice grains/pores is elucidated, demonstrating how the method increases the initial ice nucleus density by pre‐fabricating a semi‐frozen slurry, which facilitates a transition from columnar to equiaxed grain structures. For a practical demonstration, as‐prepared scaffolds are integrated into a bilayer tissue patch using biodegradable waterborne polyurethane (WPU) for large‐scale oral mucosal reconstruction in minipigs. Systematic analyses, including histology and RNA sequencing, prove that the patch modulates the healing process toward near‐scarless mucosal remodeling via innate and adaptive immunomodulation and activation of pro‐healing genes converging on matrix synthesis and epithelialization. This study not only advances the field of ice‐templating fabrication but sets a promising precedent for scaffold‐based large‐scale tissue regeneration. [ABSTRACT FROM AUTHOR]

Recent advances in regenerative medicine provide encouraging strategies to produce artificial skin substitutes. Gelatin scaffolds are successfully used as wound-dressing materials due to their superior properties, such as biocompatibility and the ability to mimic the extracellular matrix of the surrounding environment. In this study, five gelatin combination solutions were prepared and successfully electrospun using an electrospinning technique. After careful screening, the optimal concentration of the most promising combination was selected for further investigation. The obtained scaffolds were crosslinked with 25% glutaraldehyde vapor and characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. The incorporation of antibiotic agents such as ciprofloxacin hydrochloride and gentamicin sulfate into gelatin membranes improved the already existing antibacterial properties of antibiotic-free gelatin scaffolds against Pseudomonas aeruginosa and Staphylococcus aureus. Also, the outcomes from the in vivo model study revealed that skin regeneration was significantly accelerated with gelatin/ciprofloxacin scaffold treatment. Moreover, the gelatin nanofibers were found to strongly promote the neoangiogenic process in the in vivo chick embryo chorioallantoic membrane assay. Finally, the combination of gelatin's extracellular matrix and antibacterial agents in the scaffold suggests its potential for effective wound-healing treatments, emphasizing the importance of gelatin scaffolds in tissue engineering. [ABSTRACT FROM AUTHOR]

Background: In bone tissue engineering segment, numerous approaches have been investigated to address critically sized bone defects via 3D scaffolds, as the amount of autologous bone grafts are limited, accompanied with complications on harvesting. Moreover, the use of bone-marrow-derived stem cells is also a limiting factor owing to the invasive procedures involved and the low yield of stem cells. Hence, research is ongoing on the search for an ideal bone graft system promoting bone growth and regeneration. Purpose of the Study: This study aims to develop a unique platform for tissue development via stem cell differentiation towards an osteogenic phenotype providing optimum biological cues for cell adhesion, differentiation and proliferation using biomimetic gelatin-based scaffolds. The use of adipose-derived mesenchymal stem cells in this study also offers an ideal approach for the development of an autologous bone graft. Methods: A gelatin-vinyl acetate-based 3D scaffold system incorporating Bioglass was developed and the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs) on the highly porous freeze-dried gelatin-vinyl acetate/ Bioglass scaffold (GB) system was analyzed. The physicochemical properties, cell proliferation and viability were investigated by seeding rat adipose tissue-derived mesenchymal stem cells (ADSCs) onto the scaffolds. The osteogenic differentiation potential of the ADMSC seeded GeVAc/bioglass system was assessed using calcium deposition assay and bone-related protein and genes and comparing with the 3D Gelatin vinyl acetate coppolymer (GeVAc) constructs. Results and Conclusion: According to the findings, the 3D porous GeVAc/bioglass scaffold can be considered as a promising matrix for bone tissue regeneration and the 3D architecture supports the differentiation of the ADMSCs into osteoblast cells and enhances the production of mineralized bone matrix. [ABSTRACT FROM AUTHOR]

Poly(lactic acid) (PLA) is widely used in the field of medicine due to its biocompatibility, versatility, and cost-effectiveness. Three-dimensional (3D) printing or the systematic deposition of PLA in layers has enabled the fabrication of customized scaffolds for various biomedical and clinical applications. In tissue engineering and regenerative medicine, 3D-printed PLA has been mostly used to generate bone tissue scaffolds, typically in combination with different polymers and ceramics. PLA's versatility has also allowed the development of drug-eluting constructs for the controlled release of various agents, such as antibiotics, antivirals, anti-hypertensives, chemotherapeutics, hormones, and vitamins. Additionally, 3D-printed PLA has recently been used to develop diagnostic electrodes, prostheses, orthoses, surgical instruments, and radiotherapy devices. PLA has provided a cost-effective, accessible, and safer means of improving patient care through surgical and dosimetry guides, as well as enhancing medical education through training models and simulators. Overall, the widespread use of 3D-printed PLA in biomedical and clinical settings is expected to persistently stimulate biomedical innovation and revolutionize patient care and healthcare delivery. [ABSTRACT FROM AUTHOR]

BACKGROUND: Polymeric electrospun mats have been used as scaffolds in tissue engineering for the development of novel materials due to its characteristics. The usage of synthetic materials has gone in decline due to environmental problems associated with their synthesis and waste disposal. Biomaterials such as biopolymers have been used recently due to good compatibility on biological applications and sustainability. OBJECTIVE: The purpose of this work is to obtain novel materials based on synthetic and natural polymers for applications on tissue engineering. METHODS: Aloe vera mucilage was obtained, chemically characterized, and used as an active compound contained in electrospun mats. Polymeric scaffolds were obtained in single, coaxial and tri-layer structures, characterized and evaluated in cell culture. RESULTS: Mucilage loaded electrospun fibers showed good compatibility due to formation of hydrogen bonds between polymers and biomolecules from its structure, evidenced by FTIR spectra and thermal properties. Cell viability test showed that most of the obtained mats result on viability higher than 75%, resulting in nontoxic materials, ready to be used on scaffolding applications. CONCLUSION: Mucilage containing fibers resulted on materials with potential use on scaffolding applications due to their mechanical performance and cell viability results. [ABSTRACT FROM AUTHOR]

BACKGROUND: β-tricalcium phosphate (β-TCP) has been successfully utilized as a 3D printed ceramic scaffold in the repair of non-healing bone defects; however, it requires the addition of growth factors to augment its regenerative capacity. Synthetic bone mineral (SBM) is a novel and extrudable carbonate hydroxyapatite with ionic substitutions known to facilitate bone healing. However, its efficacy as a 3D printed scaffold for hard tissue defect repair has not been explored. OBJECTIVE: To evaluate the biocompatibility and cell viability of human osteoprecursor (hOP) cells seeded on 3D printed SBM scaffolds via in vitro analysis. METHODS: SBM and β-TCP scaffolds were fabricated via 3D printing and sintered at various temperatures. Scaffolds were then subject to qualitative cytotoxicity testing and cell proliferation experiments utilizing (hOP) cells. RESULTS: SBM scaffolds sintered at lower temperatures (600 °C and 700 °C) induced greater levels of acute cellular stress. At higher sintering temperatures (1100 °C), SBM scaffolds showed inferior cellular viability relative to β-TCP scaffolds sintered to the same temperature (1100 °C). However, qualitative analysis suggested that β-TCP presented no evidence of morphological change, while SBM 1100 °C showed few instances of acute cellular stress. CONCLUSION: Results demonstrate SBM may be a promising alternative to β-TCP for potential applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Cryogels represent a valid strategy as scaffolds for tissue engineering. In order to adequately support adhesion and proliferation of anchorage-dependent cells, different polymers need to be combined within the same scaffold trying to mimic the complex features of a natural extracellular matrix (ECM). For this reason, in this work, gelatin (Gel) and chondroitin sulfate (CS), both functionalized with methacrylic groups to produce CSMA and GelMA derivatives, were selected to prepare cryogel networks. Both homopolymer and heteropolymer cryogels were produced, via radical crosslinking reactions carried out at −12 °C for 2 h. All the scaffolds were characterized for their mechanical, swelling and morphological properties, before and after autoclave sterilization. Moreover, they were evaluated for their biocompatibility and ability to support the adhesion of human gingival fibroblasts and tenocytes. GelMA-based homopolymer networks better withstood the autoclave sterilization process, compared to CSMA cryogels. Indeed, GelMA cryogels showed a decrease in stiffness of approximately 30%, whereas CSMA cryogels of approximately 80%. When GelMA and CSMA were blended in the same network, an intermediate outcome was observed. However, the hybrid scaffolds showed a general worsening of the biological performance. Indeed, despite their ability to withstand autoclave sterilization with limited modification of the mechanical and morphological properties, the hybrid cryogels exhibited poor cell adhesion and high LDH leakage. Therefore, not only do network components need to be properly selected, but also their combination and ability to withstand effective sterilization process should be carefully evaluated for the development of efficient scaffolds designed for tissue engineering purposes. [ABSTRACT FROM AUTHOR]

New gelatin methacryloyl (GelMA)—strontium-doped nanosize hydroxyapatite (SrHA) composite hydrogel scaffolds were developed using UV photo-crosslinking and 3D printing for bone tissue regeneration, with the controlled delivery capacity of strontium (Sr). While Sr is an effective anti-osteoporotic agent with both anti-resorptive and anabolic properties, it has several important side effects when systemic administration is applied. Multi-layer composite scaffolds for bone tissue regeneration were developed based on the digital light processing (DLP) 3D printing technique through the photopolymerization of GelMA. The chemical, morphological, and biocompatibility properties of these scaffolds were investigated. The composite gels were shown to be suitable for 3D printing. In vitro cell culture showed that osteoblasts can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-SrHA hydrogel has good cell viability and biocompatibility. The GelMA-SrHA composites are promising 3D-printed scaffolds for bone repair. [ABSTRACT FROM AUTHOR]

This study investigates recent advancements in drug delivery systems (DDS) for tissue engineering, emphasizing their role in the targeted and sustained release of therapeutic agents to promote tissue regeneration. It explores innovative approaches, including nanotechnology, 3D printing, and immunomodulation, which enhance the effectiveness of tissue engineering therapies. This review provides a brief overview of the fundamentals of controlled drug delivery, comparing controlled release and slow release. It also introduces drug delivery vehicles, drug release mechanisms, release kinetics, and recent applications in the field of regenerative medicine. It highlights the benefits of nanotechnology, such as increased drug loading capacity and stability, and identifies 3D-printed scaffolds as a promising method for sustained drug release. Additionally, the growing interest in using DDS for immunomodulation to improve tissue regeneration is discussed. The rapidly evolving field of DDS in tissue engineering presents new opportunities for developing more effective therapeutic strategies. This study contributes to the understanding of these innovations and their potential applications. [ABSTRACT FROM AUTHOR]

Electrospun nanofiber scaffolds mimic the structure of the natural extracellular matrix, making them promising for application in tissue engineering. Based on this, the biopolymers poly(ε-caprolactone) (PCL) and gelatin, with good mechanical and biological properties, respectively, were electrospun with acetic acid as the only solvent, without the crosslinking process in order to reduce the cytotoxic effects of commonly used solvents. This study evaluated the influence of scaffold thicknesses on the physicochemical properties. Scaffolds with 4 different thicknesses were produced by increasing the electrospinning time (A = 1 h, B = 1.5 h, C = 2 h and D = 3 h). Thicker scaffolds (B, C and D, 0.142 ± 0.029 to 0.306 ± 0.053 nm) were manipulated easily, presented higher mechanical strength (from 156.21 to 178.53%) and smaller diameter fibers (approximately 300.0 nm). On the other hand, the longer the processing time, the less uniform the fibers and more melting regions between fibers, which may hinder the use of the scaffold and should be considered. Only the thickest scaffold (D) showed higher wettability (contact angle 31.1° ± 3°). Intermediate thickness scaffolds showed less beads and fiber irregularities. Cell adhesion was good due to gelatin, though cell proliferation remained constant for the thicker scaffold indicating that longer processing time may not be advantageous for cell application. Results showed that intermediate thickness scaffolds of PCL/gelatin (0.142 ± 0.029 to 0.195 ± 0.034 nm) assure good physicochemical properties to be applied for different cell types. [ABSTRACT FROM AUTHOR]

Novel scaffolds of chitosan-reduced functionalized graphene oxide (CH-rfGO) containing different values of hydroxyapatite nanoparticles (npHA) were prepared. npHA was synthesized and rfGO was obtained by the reduction and functionalization of single-layer GO nanosheets. The CH-rfGO scaffolds containing 0, 0.5, 1 and 1.5 g HA were fabricated by freeze-drying technique. The properties of the synthesized materials and the fabricated scaffolds were investigated using FTIR, XRD, FESEM and the rheology analyzer. The compressive strength, pore size and thickness of the pore walls of the scaffolds were measured. According to the FTIR and XRD results, rfGO and npHA were successfully synthesized. The interactions between HA and CH-rfGO were confirmed by XRD. The prepared scaffolds were superhydrophilic and highly porous with a hemispherical morphology that was interconnected. HA significantly changed the porous structure, pore size and pore wall thickness of scaffolds. HA increased the pore wall thickness, but the pore size first increased and then decreased; the average values were 80–230 µm (for 0, 0.5 and 1.5 HA) and 230–480 µm (for 1 HA). With regard to the rheological behavior of the slurries, the behavior of shear thinning was observed. The viscosity and shear stress changed with HA, being highest for the 1 HA sample. HA significantly improved the compressive strength of the scaffolds, reaching 963 kPa for 1.5 HA. [ABSTRACT FROM AUTHOR]