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Purpose: To assess the healing process of the extraction socket and the dimensional changes that occur after alveolar ridge preservation utilizing a polylactide-co-glycolide scaffold (PLGA). Materials and Methods: The present study involved the extraction of 28 teeth from 14 patients. The total number of sockets was 28, which were divided into two groups consisting of 14 test sockets and 14 control sockets. The study group (SG) was subjected to socket preservation with a PLGA scaffold while the control group (CG) was left for spontaneous healing. The dimensions were measured before and after operation at 1, 3, and 5 mm below the alveolar crest horizontally and the height of buccolingual bone vertically. Results: According to the histologic analyses, the PLGA scaffold was resorbed within 4 months. CBCT imaging revealed a decrease in the horizontal crest dimension at three distinct coronoapical levels in SG, measuring 2.05 ± 1.05 mm at -1 mm, 1.51 ± 0.89 mm at -3 mm, and 0.92 ± 0.7 mm at -5 mm. CG showed readings of 1.22 ± 1 at -1 mm, 0.92 ± 0.67 at -3 mm, and 0.73 ± 0.69 at -5 mm. In comparison to CG, SG showed a significant reduction in horizontal losses at -1 mm. Vertical crest dimensions decreased by 1.64 ± 1.11 mm for the buccal bone height and by 1.56 ± 1.08 mm for lingual bone height in SG; in CG, the buccal and lingual bone height had mean values of 2.08 ± 1.44 mm and 1.73 ± 1.27 mm, respectively. There was no statistically significant difference observed in the vertical losses between the groups. Conclusions: Following a period of 4 months, the PLGA scaffold was completely resorbed. Based on CBCT measurements, horizontal resorption was lower than CG at -1 mm coronally. [ABSTRACT FROM AUTHOR]

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.

Purpose: To compare bone substitutes composed of glycated collagen with synthetic micro-sized (1 to 10 µm) hydroxyapatite (OB) vs non-cross-linked collagen matrix with large-particle (250 to 1,000 µm) bovine-derived hydroxyapatite (BOC). Materials and Methods: The P1 to P4 premolars were bilaterally extracted from the mandibles of 19 Beagle dogs. After 21 days, osteotomies were created in each dog that received OB or BOC and were covered with a collagen membrane or were left untreated. The animals were randomly divided into three groups based on sacrifice time (4, 12, or 24 weeks). The right and left hemimandibles were trimmed to facilitate imaging and histology, and all tissues were placed in 10% neutral-buffered formalin. Microcomputed tomography (MicroCT 40 Scanner, Scanco) was used to analyze bone sections. Bone volume, residual material volume, and bone mineral density were determined for each treatment site (OB and BOC) based on a volume of interest that encompassed the original defect. Additionally, blinded histopathologic assessment (based on the ISO 10993-6 scoring system) and histomorphometry were performed on sections ground to < 100 µm thick and stained with Stevenel's blue. Results: No clinical side effects were noted. No statistical differences were observed for OB vs BOC regarding the mineral volume percentage. Compared to OB, BOC had significantly higher mean mineralization densities at 12 weeks (P < .01), but this difference did not extend to 24 weeks. For residual grafting material, bone maturation, alveolar ridge restoration, and inflammatory response, OB showed a residual amount of bone graft and no statistical differences compared to BOC. Conclusion: Both OB and BOC represent valid treatment options for critically sized bone defects. Both bone fillers outperformed the sham-operated, ungrafted (empty) control, demonstrating statistically improved bone growth and ridge restoration. [ABSTRACT FROM AUTHOR]

Performing soft tissue augmentation (STA) at implant sites to improve esthetics, patient satisfaction, and peri-implant health is common. Several soft tissue grafting materials can be used to increase soft tissue thickness at the second-stage surgery, including human dermal matrices and xenogeneic collagen scaffolds. This study assessed and compared the volumetric outcomes, from second-stage surgery to crown delivery, around implants that received STA with a xenogeneic cross-linked collagen scaffold (XCCS) vs nonaugmented implant sites. Thirty-one patients (31 implant sites) completed the study. Intraoral digital scans were taken at the second stage and prior to crown delivery, and the STL files were imported in an image-analysis software to assess volumetric changes. XCCS-augmented implants showed significantly greater volumetric changes compared to control sites, which showed volume loss. The mean thickness of the XCCS-augmented area was 0.73 mm. There was no difference in patient-reported esthetic evaluations between groups. STA with XCCS provided significantly greater volumetric outcomes compared to nonaugmented sites. Further studies are needed to evaluate the long-term behavior of the augmented peri-implant mucosa and the effects of STA on peri-implant health. [ABSTRACT FROM AUTHOR]

Skinless, hierarchical porous 3D polymer scaffolds are of critical importance in tissue engineering, enabling improved cell infiltration, nutrient, metabolite and energy exchange, and biomimetic structures, crucial for regenerative medicine, drug delivery, and advanced material applications. However, it is still a great challenge to construct this kind of material with traditional 3D printing techniques. Herein, a novel simple, and versatile in situ precipitation‐assisted direct‐write‐3D printing strategy for skinless, hierarchical porous 3D scaffolds is reported. Homogenous ink containing molecularly dissolved fructose (soluble porogen molecule) and polymer (whether it is hydrophilic, hydrophobic or amphiphilic) is directly extruded into a nonsolvent bath, where simultaneously solidification of the polymer and in situ precipitation of the porogen molecules both on the exterior surface and inside the separated polymer fibers happen. Subsequently, by simply leaching the in situ formed porogen particles, skinless hierarchical porous polymeric 3D scaffolds can be obtained. It is believed that 3D printing, polymer/macromolecule‐based scaffolds, especially the skinless hierarchical porous biomaterials, and the tissue engineering market can benefit tremendously from this simple and versatile approach. [ABSTRACT FROM AUTHOR]

Bioactive ceramic bone scaffolds are limited by their brittleness. To address this limitation, we developed a new method for preparing β-tricalcium phosphate (β-TCP)/polycaprolactone (PCL) porous composite scaffolds with a gradient structure using digital light processing technology and an impregnation process. The composite scaffolds exhibited compressive strength comparable to that of pure β-TCP scaffolds but with substantially higher toughness and reliability, especially during in vitro degradation. Owing to the gradient structure, the composite scaffolds could gradually shift from high strength and stiffness to moderate strength and low stiffness, which is beneficial for bone healing and remodeling. In femoral condyle defects without mechanical stimulation, the β-TCP/PCL composite scaffolds exhibited slightly lower cellular compatibility and osteoinductive ability than those of the pure β-TCP scaffolds. However, in radial defects, composite scaffolds demonstrated a better mechanical response and bone growth capacity. The composite scaffolds maintained their structural integrity after 2–4 months, whereas the β-TCP scaffolds fractured within 2 months. This study provides a novel methodology for the development of effective scaffold fabrication strategies for load-bearing or large segmental defects with complex stress applications for use in bone healing and remodeling. [ABSTRACT FROM AUTHOR]

Recent interest in tissue engineering (TE) has focused on electrically conductive biomaterials. This has been inspired by the characteristics of the cells' microenvironment where signalling is supported by electrical stimulation. Numerous studies have demonstrated the positive influence of electrical stimulation on cell excitation to proliferate, differentiate, and deposit extracellular matrix. Even without external electrical stimulation, research shows that electrically active scaffolds can improve tissue regeneration capacity. Tissues like bone, muscle, and neural contain electrically excitable cells that respond to electrical cues provided by implanted biomaterials. To introduce an electrical pathway, TE scaffolds can incorporate conductive polymers, metallic nanoparticles, and ceramic nanostructures. However, these materials often do not meet implantation criteria, such as maintaining mechanical durability and degradation characteristics, making them unsuitable as scaffold matrices. Instead, depositing conductive layers on TE scaffolds has shown promise as an efficient alternative to creating electrically conductive structures. A stratified scaffold with an electroactive surface synergistically excites the cells through active top-pathway, with/without electrical stimulation, providing an ideal matrix for cell growth, proliferation, and tissue deposition. Additionally, these conductive coatings can be enriched with bioactive or pharmaceutical components to enhance the scaffold's biomedical performance. This review covers recent developments in electrically active biomedical coatings for TE. The physicochemical and biological properties of conductive coating materials, including polymers (polypyrrole, polyaniline and PEDOT:PSS), metallic nanoparticles (gold, silver) and inorganic (ceramic) particles (carbon nanotubes, graphene-based materials and Mxenes) are examined. Each section explores the conductive coatings' deposition techniques, deposition parameters, conductivity ranges, deposit morphology, cell responses, and toxicity levels in detail. Furthermore, the applications of these conductive layers, primarily in bone, muscle, and neural TE are considered, and findings from in vitro and in vivo investigations are presented. Tissue engineering (TE) scaffolds are crucial for human tissue replacement and acceleration of healing. Neural, muscle, bone, and skin tissues have electrically excitable cells, and their regeneration can be enhanced by electrically conductive scaffolds. However, standalone conductive materials often fall short for TE applications. An effective approach involves coating scaffolds with a conductive layer, finely tuning surface properties while leveraging the scaffold's innate biological and physical support. Further enhancement is achieved by modifying the conductive layer with pharmaceutical components. This review explores the under-reviewed topic of conductive coatings in tissue engineering, introducing conductive biomaterial coatings and analyzing their biological interactions. It provides insights into enhancing scaffold functionality for tissue regeneration, bridging a critical gap in current literature. [Display omitted] [ABSTRACT FROM AUTHOR]

Articular cartilage damage and wear can result in cartilage degeneration, ultimately culminating in osteoarthritis. Current surgical interventions offer limited capacity for cartilage tissue regeneration and offer only temporary alleviation of symptoms. Tissue engineering strategies are increasingly recognized as promising modalities for cartilage restoration. Currently, various biological scaffolds utilizing tissue engineering materials are extensively employed in both fundamental and clinical investigations of cartilage repair. In order to optimize the cartilage repair ability of tissue engineering scaffolds, researchers not only optimize the structure and properties of scaffolds from the perspective of materials science and manufacturing technology to enhance their histocompatibility, but also adopt strategies such as loading cells, cytokines, and drugs to promote cartilage formation. This review provides an overview of contemporary tissue engineering strategies employed in cartilage repair, as well as a synthesis of existing preclinical and clinical research. Furthermore, the obstacles faced in the translation of tissue engineering strategies to clinical practice are discussed, offering valuable guidance for researchers seeking to address these challenges. [ABSTRACT FROM AUTHOR]

Background: Different materials have been used as wound dressings after vital pulp therapies. Some of them have limitations such as delayed setting, difficult administration, slight degree of cytotoxicity, crown discoloration and high cost. Therefore, to overcome these disadvantages, composite scaffolds have been used in regenerative dentistry. This study aims to construct and characterize the physicochemical behavior of a novel injectable alginate hydrogel loaded with different bioactive glass nanoparticles in various concentrations as a regenerative pulpotomy filling material. Methods: Alginate hydrogels were prepared by dissolving alginate powder in alcoholic distilled water containing mesoporous bioactive glass nanoparticles (MBG NPs) or boron-doped MBG NPs (BMBG NPs) at 10 and 20 wt% concentrations. The mixture was stirred and incubated overnight in a water bath at 50 0 C to ensure complete solubility. A sterile dual-syringe system was used to mix the alginate solution with 20 wt% calcium chloride solution, forming the hydrogel upon extrusion. Then, constructed hydrogel specimens from all groups were characterized by FTIR, SEM, water uptake percentage (WA%), bioactivity and ion release, and cytotoxicity. Statistical analysis was done using One-Way ANOVA test for comparisons between groups, followed by multiple pairwise comparisons using Bonferroni adjusted significance level (p < 0.05). Results: Alginate/BMBG loaded groups exhibited remarkable increase in porosity and pore size diameter [IIB1 (168), IIB2 (183) (µm)]. Similarly, WA% increased (~ 800%) which was statistically significant (p < 0.05). Alginate/BMBG loaded groups exhibited the strongest bioactive capability displaying prominent clusters of hydroxyapatite precipitates on hydrogel surfaces. Ca/P ratio of precipitates in IIA2 and IIB1 (1.6) were like Ca/P ratio for stoichiometric pure hydroxyapatite (1.67). MTT assay data revealed that the cell viability % of human gingival fibroblast cells have declined with increasing the concentration of both powders and hydrogel extracts in all groups after 24 and 48 h but still higher than the accepted cell viability % of (˃70%). Conclusions: The outstanding laboratory performance of the injectable alginate/BMBGNPs (20 wt%) composite hydrogel suggested it as promising candidate for pulpotomy filling material potentially enhancing dentin regeneration in clinical applications. [ABSTRACT FROM AUTHOR]

Electroactive scaffolds are increasingly used to mimic the microenvironment of electroactive tissues such as the heart and nerves. Multi-network hydrogels have emerged as an important platform in the field of tissue engineering. In this study, alginate (Alg)-based conductive and multi-network nanocomposite hydrogels were prepared and characterized as promising scaffolds for electroactive tissues. Alg, which is derived from natural sources, was modified with methacrylate (AlgMA) to render it photosensitive (photoactive). Multiwall carbon nanotubes (MWCNTs) were chosen as potential nanomaterials for electrical conductivity. MWCNTs were modified with –COOH groups to produce MWCNT–COOH nanomaterials. Nanocomposite hydrogels were fabricated by incorporating 0.5%, 1.0%, and 3.0 wt% of MWCNT–COOH into the AlgMA network. The hydrogel scaffolds were assessed for their chemical, physical, mechanical, electrical, and biological characteristics. This study demonstrated that incorporating modified MWCNTs into an AlgMA network enhances its electrical activity. According to our results, good rheological properties, natural tissue-like mechanical properties, optimal electrical conductivity, and biological performance make AlgMA/MWCNT–COOH multi-network nanocomposite hydrogels crucial in the field of electroactive tissues. [ABSTRACT FROM AUTHOR]

AbstractOral diseases are a prevalent global issue, causing significant health and economic burdens that greatly diminish the quality of life for affected individuals. Tissue engineering strategies employing scaffolds offer a promising approach to restoring the original structures and biological functions of dental and dentoalveolar tissues. Among the various building materials, polysaccharides, known for their inherent biocompatibility, have gained significant attention. Topical advances in tissue engineering have led to the fabrication of composite scaffolds with the greatest utilization of favorable properties of each material. This review aims to explore the application of polysaccharide-based composite scaffolds for regenerating dental and dentoalveolar tissues, including both hard and soft tissues, as well as tissue complexes. To begin, we will provide a brief overview to commonly used polysaccharides. Subsequently, we will introduce the commonly used forms of composite polysaccharide scaffolds together with fabricating, engineering, and optimizing methods for dental and dentoalveolar tissue regeneration. Next, we will examine the latest progress and the potential of polysaccharide composite scaffolds in dental and dentoalveolar tissue regeneration applications. To conclude, this review will reflect on the limitations and prospects associated with polysaccharide composite scaffolds for dental and dentoalveolar tissue regeneration. By addressing these aspects, we aim to contribute to the understanding and development of effective strategies for improving oral health outcomes. [ABSTRACT FROM AUTHOR]

One of the challenges and limitations of bone tissue engineering includes fast degradation rates, reduced bioactivity, donor site morbidity, and unresolved risks of pathogen transmission. In the field of bone tissue engineering, gradient materials are promising for treating bone defects because they can create graded structures and compositions similar to natural bone. By controlling the amount of components in the structure, the degradation rate, bioactivity, and osteogenic capacity can be manipulated. In the current study, a gradient, multilayer, porous nanocomposite of calcium sulfate/glass (Gn CS/BG) with a gelatin coating (Gn CS/BG-Gel) was prepared using rotational casting technique. The SEM results showed an average pore size of approximately 400 μm within the Gn CS/BG-Gel nanocomposite. An elastic modulus (E) of around 240 MPa and an ultimate tensile strength (σ) of approximately 5.5 MPa were achieved for Gn CS/BG-Gel nanocomposite. The degradation analysis in a dynamic tris-buffer environment revealed a degradation rate of 68 % over a 63-day period, with a decrease in degradation rate as the bioactive glass (BG) content increased in each layer, indicating the influence of BG on the degradation process. The bioactivity results in a dynamic simulated body fluid suggested that increased BG content in each layer promoted hydroxyapatite formation, indicating improved bioactive behavior. The evaluation of ion release with ICP-OES, MTT and Acridine Orange assays using human bone marrow-derived mesenchymal stem cells (hBMSCs) confirmed the non-toxic nature of Gn CS/BG-Gel. Assessments of alkaline phosphatase (ALP) activity, calcium content, Alizarin Red staining and cell attachment behavior substantiated the osteogenic potential of Gn CS/BG-Gel. Collectively, the three-dimensional structure along with the Gn CS/BG-Gel composition contributed to the enhanced cellular responses. These findings hold significant promise for the development of biomaterials with potential applications in bone tissue engineering, and they contribute valuable insights to the field. [Display omitted] [ABSTRACT FROM AUTHOR]

Degenerative disc disease is the leading cause of lower back and leg pain, considerably impacting daily life and incurring substantial medical expenses for those affected. The development of annulus fibrosus tissue engineering offers hope for treating this condition. However, the current annulus fibrosus tissue engineering scaffolds fail to accurately mimic the natural biological environment of the annulus fibrosus, resulting in limited secretion of extracellular matrix produced by the seeded cells and poor biomechanical properties of the constructed biomimetic annulus fibrosus tissue. This inability to match the biomechanical performance of the natural annulus fibrosus hinders the successful treatment of annulus fibrosus defects. In this study, we fabricated decellularized annulus fibrosus matrix (DAFM)/chitosan hydrogel-1 (DAFM: Chitosan 6:2) and DAFM/chitosan hydrogel-2 (DAFM: Chitosan 4:4) by varying the ratio of DAFM to chitosan. Rat annulus fibrosus (AF)-derived stem cells were cultured on these hydrogel scaffolds, and the cell morphology, AF-related gene expression, and Interleukin-6 (IL-6) levels were investigated. Additionally, magnetic resonance imaging, Hematoxylin and eosin staining, and Safranine and Fast Green staining were performed to evaluate the repair effect of the DAFM/chitosan hydrogels in vivo. The gene expression results showed that the expression of Collagen type I (Col-I), Collagen type I (Col-II), and aggrecan by annulus fibrosus stem cells (AFSCs) cultured on the DAFM/chitosan-1 hydrogel was higher compared with the DAFM/chitosan-2 hydrogel. Conversely, the expression of metalloproteinase-9 (MMP-9) and IL-6 was lower on the DAFM/chitosan-1 hydrogel compared with the DAFM/chitosan-2 hydrogel. In vivo, both the DAFM/chitosan-1 and DAFM/chitosan-2 hydrogels could partially repair large defects of the annulus fibrosus in rat tail vertebrae. In conclusion, the DAFM/chitosan-1 hydrogel could be regarded as a candidate scaffold material for the repair of annulus fibrosus defects, offering the potential for improved treatment outcomes. [ABSTRACT FROM AUTHOR]

Many withered leaves or flowers spontaneously curl and transform from flattened structures into tubular constructs upon dehydration. Inspired by this phenomenon, an innovative strategy is developed to design stimuli‐responsive scaffolds that are capable of programmable transformation from flattened 2D constructs into various curled 3D tissue‐mimicking structures. Specifically, Janus‐structured scaffolds consisting of a passive layer of polycaprolactone and an active, triggered‐transforming layer of methacrylate gelatin/alginate hydrogel are 3D‐printed, which replicate the asymmetrical structure of leaves and enabled on‐demand transformation into desired curvatures and shapes through mimicking the regulation mechanism of leaves curling behavior by mesophyll matrix stiffness and vein patterns. Particularly for vascular reconstruction, multi‐step transformation scaffolds capable of primary 2D‐to‐3D transformation into tubular constructs induced by dehydration, and secondary transformation to adapt to the local intravascular geometry in vivo, are successfully developed. In addition, the oriented polycaprolactone layer of the printed scaffold can enable the adhesion, proliferation, and orientation of endothelial cells, thus demonstrating a novel strategy for the design of tissue‐engineered blood vessels. In general, this study provides an innovative design strategy for programmable biomaterials capable of shape morphing and adaptation in physiological conditions, thereby opening up a new avenue for the design of intelligent biomaterials in regenerative medicine. [ABSTRACT FROM AUTHOR]

The electrospinning process is an effective technique for creating micro- and nanofibers from synthetic and natural polymers, with significant potential for biomedical applications and drug delivery systems due to their high drug-loading capacity, large surface area, and tunable release times. Poly(L-lactic acid) (PLLA) stands out for its excellent thermo-mechanical properties, biodegradability, and bioabsorbability. Electrospun PLLA nanofibrous structures have been extensively investigated as wound dressings, sutures, drug delivery carriers, and tissue engineering scaffolds. This study aims to create and characterize electrospun PLLA membranes loaded with spironolactone (SP), mimicking active compounds of Ganoderma lucidum (GL), to develop a biodegradable patch for topical wound-healing applications. GL, a medicinal mushroom, enhances dermal wound healing with its bioactive compounds, such as polysaccharides and ganoderic acids. Focusing on GL extracts—obtained through green extraction methods—and innovative drug delivery, we created new fibers for wound-healing potential applications. To integrate complex mixtures of bioactive compounds into the fibers, we developed a prototype using a single pure substance representing the extract mixture. This painstaking work presents the results of the fabricating, wetting, moisture properties, material resilience, and full characterization of the product, providing a robust rationale for the fabrication of fibers imbued with more complex extracts. [ABSTRACT FROM AUTHOR]

Objectives: The high porosity of tissue engineering scaffolds is advantageous as they provide a high degree of infiltration of nutrients, enable cell penetration, and support vascularisation. However, the mechanical strength is also critical for providing structural support to the defect site throughout the regeneration process. In this study, we aimed to establish a relationship between internal phase volume and emulsion-templated scaffolds' physical, morphological and mechanical characteristics. Methods: In this work, tetra methacrylate functionalised polycaprolactone (4PCLMA) polymers were synthesised via ring-opening polymerisation followed by methacrylation. 4PCLMA-based emulsion templated matrices with 60%, 75% and 82% internal phase volumes were fabricated (P60, P75, and P82). These scaffolds' densities, porosities, average pore and window sizes, degree of interconnectivity values, and mechanical properties were investigated. Results: Increasing internal phase volume reduced the density of the foams by almost two-fold. No direct correlation was observed between average pore size and internal phase volume. Both the average window sizes and the degree of interconnectivity values increase with increasing internal phase volume. Compression modulus values are calculated as 0.46±0.04 MPa, 0.23±0.02 MPa and 0.14±0.01 MPa for P60, P75, and P82, respectively. Increasing internal phase volume from 60% to 82% caused a more than 2-fold reduction in the stiffness of the emulsion-templated matrices. Conclusions: Accordingly, by reporting on this experimental framework, we established a relationship between internal phase volume and the physical, morphological and mechanical characteristics of 4PCMA-based scaffolds to precisely engineer these characteristics for specific tissue engineering applications. [ABSTRACT FROM AUTHOR]

Fe-Ca-SAPO-34/CS/PANI, a novel hybrid bio-composite scaffold with potential application in dental tissue engineering, was prepared by freeze drying technique. The scaffold was characterized using FT-IR and SEM methods. The effects of PANI on the physicochemical properties of the Fe-Ca-SAPO-34/CS scaffold were investigated, including changes in swelling ratio, mechanical behavior, density, porosity, biodegradation, and biomineralization. Compared to the Fe-Ca-SAPO-34/CS scaffold, adding PANI decreased the pore size, porosity, swelling ratio, and biodegradation, while increasing the mechanical strength and biomineralization. Cell viability, cytotoxicity, and adhesion of human dental pulp stem cells (hDPSCs) on the scaffolds were investigated by MTT assay and SEM. The Fe-Ca-SAPO-34/CS/PANI scaffold promoted hDPSC proliferation and osteogenic differentiation compared to the Fe-Ca-SAPO-34/CS scaffold. Alizarin red staining, alkaline phosphatase activity, and qRT-PCR results revealed that Fe-Ca-SAPO-34/CS/PANI triggered osteoblast/odontoblast differentiation in hDPSCs through the up-regulation of osteogenic marker genes BGLAP, RUNX2, and SPARC. The significance of this study lies in developing a novel scaffold that synergistically combines the beneficial properties of Fe-Ca-SAPO-34, chitosan, and PANI to create an optimized microenvironment for dental tissue regeneration. These findings highlight the potential of the Fe-Ca-SAPO-34/CS/PANI scaffold as a promising biomaterial for dental tissue engineering applications, paving the way for future research and clinical translation in regenerative dentistry. [ABSTRACT FROM AUTHOR]

Tendinopathy is a leading cause of mobility issues. Currently, the cell–matrix interactions involved in the development of tendinopathy are not fully understood. In vitro tendon models provide a unique tool for addressing this knowledge gap as they permit fine control over biochemical, micromechanical, and structural aspects of the local environment to explore cell–matrix interactions. In this study, direct-write, near-field electrospinning of gelatin solution was implemented to fabricate micron-scale fibrous scaffolds that mimic native collagen fiber size and orientation. The stiffness of these fibrous scaffolds was found to be controllable between 1 MPa and 8 MPa using different crosslinking methods (EDC, DHT, DHT+EDC) or through altering the duration of crosslinking with EDC (1 h to 24 h). EDC crosslinking provided the greatest fiber stability, surviving up to 3 weeks in vitro. Differences in stiffness resulted in phenotypic changes for equine tenocytes with low stiffness fibers (∼1 MPa) promoting an elongated nuclear aspect ratio while those on high stiffness fibers (∼8 MPa) were rounded. High stiffness fibers resulted in the upregulation of matrix metalloproteinase (MMPs) and proteoglycans (possible indicators for tendinopathy) relative to low stiffness fibers. These results demonstrate the feasibility of direct-written gelatin scaffolds as tendon in vitro models and provide evidence that matrix mechanical properties may be crucial factors in cell–matrix interactions during tendinopathy formation. [ABSTRACT FROM AUTHOR]

Here, a novel kind of composite scaffold was fabricated by loading vascular endothelial growth factor (VEGF) and gastrodin liposome (GAS-LP) into electrospun silk fibroin/graphene oxide(SF/GO)nanofibrous and silk fibroin sponge-filled, respectively. Our results demonstrated that VEGF and GAS exhibited different release patterns in vitro which VEGF showed rapid release rate in the first few days while GAS was released slowly and continuously as encapsulated in liposomes. The scaffolds realized the combination of intraneural vascularization drugs and electrical stimulation effectively, leading to enhanced growth of RSC96 cells. Furthermore, the scaffolds could protect RSC96 cells in an inflammatory environment. [ABSTRACT FROM AUTHOR]

Nerve repair and regeneration are still challenging issues in the world, mainly due to the complex anatomic structure and limited regeneration ability of natural nerves. Tissue engineering provides a structure and function similar to nerve tissue through scaffold materials, seed cells, and active factors, which is a promising method to treat nerve injury. Gelatin methacrylate (GelMA) hydrogel is a kind of gelatin modified by methacrylamide, which possesses adjustable mechanical properties, convenient processability, and excellent biocompatibility, has been widely used in nerve tissue engineering. In this paper, the research progress of GelMA-based hydrogel in nerve repair and regeneration in recent five years is reviewed, with emphasis on the advanced manufacturing technologies of three-dimensional (3D) GelMA scaffold and the application systems that can effectively promote nerve repair and regeneration. We also evaluated the challenges and prospects of GelMA-based hydrogels in the field of nerve repair and regeneration, which is of guiding significance to the research of nerve tissue engineering. [ABSTRACT FROM AUTHOR]

Revitalization has emerged as an innovative treatment approach for immature permanent teeth with necrotic pulp. This article presents a comprehensive analysis of revitalization, focusing on its principles, clinical protocols and outcomes. The article highlights the importance of thorough diagnosis and assessment of the pulp and peri-apical condition to determine the suitability of revitalization. Various factors influencing the success of revitalization, such as the use of scaffolds, growth factors and stem cells, are discussed. Additionally, a case that was treated with a PRP scaffold is also presented. Overall, revitalization shows promise in promoting pulp regeneration and improving treatment outcomes in selected cases of pulp necrosis. CPD/Clinical Relevance: To introduce research-based knowledge to GDPs about the procedure and prognosis of tooth revitalization. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop multifunctional magnetic poly(ε‐caprolactone) (PCL) mats with antibacterial properties for bone tissue engineering and osteosarcoma prevention. To provide good dispersion of magnetic iron oxide nanoparticles (IONs), they were first grafted with PCL using a novel three‐step approach. Then, a series of PCL‐based mats containing a fixed amount of ION@PCL particles and an increasing content of ascorbic acid (AA) was prepared by electrospinning. AA is known for increasing osteoblast activity and suppressing osteosarcoma cells. Composites were characterized in terms of morphology, mechanical properties, hydrolytic stability, antibacterial performance, and biocompatibility. AA affected both the fiber diameter and the mechanical properties of the nanocomposites. All produced mats were nontoxic to rat bone marrow‐derived mesenchymal cells; however, a composite with 5 wt.% of AA suppressed the initial proliferation of SAOS‐2 osteoblast‐like cells. Moreover, AA improved antibacterial properties against Staphylococcus aureus and Escherichia coli compared to PCL. Overall, these magnetic composites, reported for the very first time, can be used as scaffolds for both tissue regeneration and osteosarcoma prevention. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: There are different situations in which an extrahepatic bile duct replacement or substitute is needed, such as initial and localized stages of bile duct cancer, agenesis, stenosis, or bile duct disruption. Materials and Methods: A prosthesis obtained by electrospinning composed of Poly (D,L-lactide-co-glycolide) (PGLA) - Polycaprolactone (PCL) - Gelatin (Gel) was developed, mechanical and biological tests were carried out to evaluate resistance to tension, biocompatibility, biodegradability, cytotoxicity, morphological analysis and cell culture. The obtained prosthesis was placed in the extrahepatic bile duct of 15 pigs with a 2-year follow-up. Liver function tests and cholangioscopy were evaluated during follow-up. Results: Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable. The prosthesis implanted in the experimental model allowed cell adhesion, migration, and proliferation, maintaining bile duct permeability without altering liver function tests. Immunohistochemical analysis indicates the presence of biliary epithelium. Conclusions: A tubular scaffold composed of electrospun PGLA-PCL-Gel nanofibers was used for the first time to replace the extrahepatic bile duct in pigs. Mechanical and biological evaluations indicate that this scaffold is biocompatible and biodegradable, making it an excellent candidate for use in bile ducts and potentially in other tissue engineering applications. [ABSTRACT FROM AUTHOR]

Tissue engineering is a set of techniques for producing or reconstructing tissue that primarily aims to restore or improve the function of tissues in the human body. The aim of the present study was to evaluate the mechanical and histological characteristics of decellularized tracheal scaffolds prepared in comparison with fresh trachea for use in tracheal repair. In order to prepare the scaffold, sheep's trachea was prepared and after cleaning the waste tissues, they were decellularized. Then decellularized scaffolds were evaluated histologically and laboratory and numerical study of the nonlinear mechanical behavior of tracheal tissue and scaffold and their comparison. Examining the results of histological evaluations showed that the decellularization of the scaffolds was completely done. These results were confirmed by hematoxylin–eosin staining. Also, the exact hyperelastic properties of tracheal tissue and scaffold were used in biomechanical models, and according to the presented results, the five-term Mooney–Rivlin strain energy density function became a suitable behavioral model for modeling the hyperelastic behavior of trachea and scaffold. In total, the results of this research showed that the scaffolds obtained from decellularization by preserving the main compositions of the desired tissue can be a suitable platform for investigating cell behaviors. [ABSTRACT FROM AUTHOR]

Osteomyelitis is a complex infectious disease caused by bacterial infection, which has always been a difficult problem for clinical orthopedic surgeons. Although the traditional methods are effective in treating osteomyelitis, the heavy use of antibiotics and surgical treatment cause serious side effects and lead to bone loss and healing difficulties after surgery. Chitosan (CS), a natural polymer material, is a deacetylated derivative of chitin, which has good biodegradability, antibacterial, and osteogenic properties, and has been widely used in the treatment of osteomyelitis. In this review, the recent research progress in the application of CS based composites such as micro-nano drug delivery carriers, hydrogels, coating materials, and bone tissue engineering scaffolds for the treatment of osteomyelitis is summarized, in order to provide certain experimental and theoretical support for the development of CS based composites. [ABSTRACT FROM AUTHOR]

Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel scaffold was superior to MSC-embedded Pluronic hydrogel in supporting tissue development and vascularization of a subcutaneous site. While the scaffold alone promoted vascular tissue formation, the inclusion of MSCs in the bio-ink further enhanced angiogenesis. Our findings highlight the use of simple cell-laden degradable bioprinted structures to generate a supportive microenvironment for cell delivery. [ABSTRACT FROM AUTHOR]

This study investigates the synthesis of hydroxyapatite nanoparticles via aqueous precipitation at pH 9 and Ca/P molar ratio of 1.67, exploring the effects of various synthesis parameters. Moreover, porous hydroxyapatite scaffolds were created using a pore-forming agent. These parameters' effects on the crystal structure, chemical composition, morphology, porosity, and pore size of hydroxyapatite powders and porous scaffolds were determined by various analytical techniques such as x-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), simultaneous thermal analysis (TGA/DSC), electron microscopy (SEM), pycnometry, and optical microscopy (OM). The XRD results revealed good crystallization of the hydroxyapatite with the formation of TCP and TTCP secondary phases resulting from the decomposition of hydroxyapatite (HA). The FTIR spectra of sintered HA confirmed the presence of the main absorption bands corresponding to phosphate and hydroxide groups with different peaks in intensity. The TGA/DSC analysis confirmed the results previously obtained by FTIR and XRD. SEM analysis showed the formation of various shapes of hydroxyapatite nanoparticles. According to different synthesis parameters, a porous HA scaffold up to 61% porosity can be prepared using ammonium bicarbonate as a pore-forming agent. [ABSTRACT FROM AUTHOR]

Extrusion-based three-dimensional (3D) printing of gelatin (Gel) is crucial for fabricating bone tissue engineering scaffolds via additive manufacturing. However, the thermal instability of Gel remains a persistent challenge, as it tends to collapse at mild temperatures. Current approaches often involve simply mixing Gel particles with various materials, resulting in biomaterial inks that lack uniformity and have inconsistent degradation characteristics. In this study, acetic acid was used to dissolve Gel and polycaprolactone (PCL) separately, producing homogeneous Gel/PCL dispersions with optimal pre-treatment performance. These dispersions were then combined and hybridized with nano-hydroxyapatite (n-HA) to create a composite printing ink. By evaluating the printability of the ink, the optimal conditions were identified: a n-HA concentration of 50% (w/w), a printing temperature of 10–15 ℃, a printing pressure of 2.5 bar, and a printing speed of 7 mm/s. The resulting biomaterial inks, with a composition of 25% Gel, 25% PCL, and 50% n-HA, demonstrated excellent printability and stability, along with significantly enhanced mechanical properties. As a result, 3D scaffolds with high printability and shape fidelity can be printed at room temperature, followed by deep freezing at -80 ℃ and cross-linking with vanillin. The Gel-based composite scaffolds demonstrated excellent biocompatibility, cell adhesion, cell viability and nano-hydroxyapatite absorption in vitro. Additionally, in vivo experiments revealed that the bioactive scaffold biodegraded during implantation and significantly promoted bone regeneration at the defect site. This provides a promising strategy for treating bone defects in clinical setting. In conclusion, the Gel/PCL/n-HA biomaterial inks presented here offer an innovative solution for extrusion bioprinting in the field of bone tissue engineering. [ABSTRACT FROM AUTHOR]

The development of tissue engineering and regeneration research has created new platforms for bone transplantation. However, the preparation of scaffolds with good fiber integrity is challenging, because scaffolds prepared by traditional printing methods are prone to fiber cracking during solvent evaporation. Human skin has an excellent natural heat-management system, which helps to maintain a constant body temperature through perspiration or blood-vessel constriction. In this work, an electrohydrodynamic-jet 3D-printing method inspired by the thermal-management system of skin was developed. In this system, the evaporation of solvent in the printed fibers can be adjusted using the temperature-change rate of the substrate to prepare 3D structures with good structural integrity. To investigate the solvent evaporation and the interlayer bonding of the fibers, finite-element analysis simulations of a three-layer microscale structure were carried out. The results show that the solvent-evaporation path is from bottom to top, and the strain in the printed structure becomes smaller with a smaller temperature-change rate. Experimental results verified the accuracy of these simulation results, and a variety of complex 3D structures with high aspect ratios were printed. Microscale cracks were reduced to the nanoscale by adjusting the temperature-change rate from 2.5 to 0.5 °C s−1. Optimized process parameters were selected to prepare a tissue engineering scaffold with high integrity. It was confirmed that this printed scaffold had good biocompatibility and could be used for bone-tissue regeneration. This simple and flexible 3D-printing method can also help with the preparation of a wide range of micro- and nanostructured sensors and actuators. ARTICLE HIGHLIGHTS: • A controllable and cost-effective high-resolution E-jet 3d-printing fabrication technology inspired by skin thermal management was developed. • The solvent-evaporation path in the printed structure and its stress–strain development under the influence of temperature were obtained. • High-aspect-ratio 3D structures with good structural integrity were prepared by adjusting the evaporation of the solvent using the temperature-change rate. • A PCL/PVP scaffold with fiber diameters close to the size of living cells was printed, which exhibited high biocompatibility for bone-tissue regeneration. [ABSTRACT FROM AUTHOR]

AbstractTissue engineering has emerged as a biological alternative aimed at sustaining, rehabilitating, or enhancing the functionality of tissues that have experienced partial or complete loss of their operational capabilities. The distinctive characteristics of electrospun nanofibrous structures, such as their elevated surface-area-to-volume ratio, specific pore sizes, and fine fiber diameters, make them suitable as effective scaffolds in tissue engineering, capable of mimicking the functions of the targeted tissue. However, electrospun nanofibers, whether derived from natural or synthetic polymers or their combinations, often fall short of replicating the multifunctional attributes of the extracellular matrix (ECM). To address this, nanomaterials (NMs) are integrated into the electrospun polymeric matrix through various functionalization techniques to enhance their multifunctional properties. Incorporation of NMs into electrospun nanofibrous scaffolds imparts unique features, including a high surface area, superior mechanical properties, compositional variety, structural adaptability, exceptional porosity, and enhanced capabilities for promoting cell migration and proliferation. This review provides a comprehensive overview of the various types of NMs, the methodologies used for their integration into electrospun nanofibrous scaffolds, and the recent advancements in NM-functionalized electrospun nanofibrous scaffolds aimed at regenerating bone, cardiac, cartilage, nerve, and vascular tissues. Moreover, the main challenges, limitations, and prospects in electrospun nanofibrous scaffolds are elaborated. [ABSTRACT FROM AUTHOR]

Background: Bone defects, especially critical-size bone defects, and their repair pose a treatment challenge. Osteoinductive scaffolds have gained importance given their potential in bone tissue engineering applications. Methods: Polycaprolactone (PCL) scaffolds are used for their morphological, physical, cell-compatible and osteoinductive properties. The PCL scaffolds were prepared by electrospinning, and the surface was modified by layer-by-layer deposition using either graphene or graphene oxide. Results: Graphene oxide-coated PCL (PCL-GO) scaffolds showed a trend for enhanced physical properties such as fibre diameter, wettability and mechanical properties, yield strength, and tensile strength, compared to graphene-modified PCL scaffolds (PCL-GP). However, the surface roughness of PCL-GP scaffolds showed a higher trend than PCL-GO scaffolds. In vitro studies showed that both scaffolds were cell-compatible. Graphene oxide on PCL scaffold showed a trend for enhanced osteogenic differentiation of human umbilical cord Wharton's jelly-derived Mesenchymal Stem Cells without any differentiation media than graphene on PCL scaffolds after 21 days. Conclusion: Graphene oxide showed a trend for higher mineralisation, but this trend is not statistically significant. Therefore, graphene and graphene oxide have the potential for bone regeneration and tissue engineering applications. Future in vivo studies and clinical trials are warranted to justify their ultimate clinical use. [ABSTRACT FROM AUTHOR]

Hydrogels are useful drug release systems and tissue engineering scaffolds. However, synthetic hydrogels often require harsh gelation conditions and can contain toxic by‐products while naturally derived hydrogels can transmit pathogens and in general have poor mechanical properties. Thus, there is a need for a hydrogel that forms under ambient conditions, is non‐toxic, xeno‐free, and has good mechanical properties. A recombinant spider silk protein‐derived hydrogel that rapidly forms at 37 °C is recently developed. The temperature and gelation times are well‐suited for an injectable in situ polymerising hydrogel, as well as a 3D cell culture scaffold. Here, it is shown that the diffusion rate and the mechanical properties can be tuned by changing the protein concentration and that human fetal mesenchymal stem cells encapsulated in the hydrogels show high survival and viability. Furthermore, mixtures of recombinant spider silk proteins and green fluorescent protein (GFP) form gels from which functional GFP is gradually released, indicating that bioactive molecules are easily included in the gels, maintain activity and can diffuse through the gel. Interestingly, encapsulated ARPE‐19 cells are viable and continuously produce the growth factor progranulin, which is detected in the cell culture medium over the study period of 31 days. [ABSTRACT FROM AUTHOR]

Background: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. Methods: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. Results: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). Conclusions: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we attempted to create skeletal muscle sheets made of directly converted myoblasts (dMBs) with a nanogel scaffold on a biosheet using a mouse gastroschisis model. Methods: dMBs were prepared by the co-transfection of MYOD1 and MYCL into human fibroblasts. Silicon tubes were implanted under the skin of NOG/SCID mice, and biosheets were formed. The nanogel was a nanoscale hydrogel based on cholesterol-modified pullulan, and a NanoClip-FD gel was prepared by freeze-drying the nanogel. 7 mm in length was created in the abdominal wall of NOG/SCID mice as a mouse gastroschisis model. Matrigel or NanoCliP-FD gel seeded with dMBs was placed on the biosheet and implanted on the model mice. Results: Fourteen days after surgery, dMBs with Matrigel showed a small amount of coarse aggregations of muscle-like cells. In contrast, dMBs with NanoCliP-FD gel showed multinucleated muscle-like cells, which were expressed as desmin and myogenin by fluorescent immunostaining. Conclusion: Nanogels have a porous structure and are useful as scaffolds for tissue regeneration by supplying oxygen and nutrients supply to the cells. Combining dMBs and nanogels on the biosheets resulted in the differentiation and engraftment of skeletal muscle, suggesting the possibility of developing skeletal muscle sheets derived from autologous cells and tissues. [ABSTRACT FROM AUTHOR]

In the recent years, electroconductive scaffolds have shown promising capabilities in guided regeneration of electroactive tissues including nerve, heart muscle, bone, cartilage, and skin. Herein, the fabrication of a novel electroconductive poly (L‐lactic acid) (PLLA)/polyamidoamine (PAMAM) dendrimer nanofibrous scaffold containing graphene oxide (GO) nanosheets is described. The presence of PAMAM with amine terminal groups successfully aminolyzed PLLA. Interestingly, both PAMAM (5% w/w) and GO (0.5, 1, 2% w/w) not only contributed to reducing the fiber diameter, increasing the hydrophilicity and degradation rate, but also provided a nanocomposite scaffold with enhancement in electrical conductivity. By incorporating 1% w/w of GO, the nanocomposite scaffold exhibited optimized properties, including electrical conductivity (≈3.09 × 10−5 S m−1), crystallinity (≈ 47%), Young's modulus (≈16.95 MPa), as well as strength (≈1.58 MPa). This nanocomposite also demonstrated significant antibacterial activity of ≥ 90% against both gram‐positive and gram‐negative bacteria. Cellular assays confirmed acceptable cytocompatibility of the nanocomposite scaffolds containing GO and PAMAM, which can support the viability and proliferation of PC‐12 cells. In conclusion, the presence of GO nanosheets alongside PAMAM dendrimers can synergically promote the properties of the prepared nanofibrous mats which can be used as potential electroconductive scaffolds for guided tissue regeneration. [ABSTRACT FROM AUTHOR]

Silk fibroin (SF) extracted from silk is non-toxic and has excellent biocompatibility and biodegradability, making it an excellent biomedical material. SF-based soft materials, including porous scaffolds and hydrogels, play an important role in accurately delivering drugs to wounds, creating microenvironments for the adhesion and proliferation of support cells, and in tissue remodeling, repair, and wound healing. This article focuses on the study of SF protein-based soft materials, summarizing their preparation methods and basic applications, as well as their regenerative effects, such as drug delivery carriers in various aspects of tissue engineering such as bone, blood vessels, nerves, and skin in recent years, as well as their promoting effects on wound healing and repair processes. The authors expect SF soft materials to play an important role in the field of tissue repair. [ABSTRACT FROM AUTHOR]

Bone tissue exhibits self-healing properties; however, not all defects can be repaired without surgical intervention. Bone tissue engineering offers artificial scaffolds, which can act as a temporary matrix for bone regeneration. The aim of this study was to manufacture scaffolds made of poly(lactic acid), poly(ε-caprolactone), poly(propylene fumarate), and poly(ethylene glycol) modified with bioglass, beta tricalcium phosphate (TCP), and/or wollastonite (W) particles. The scaffolds were fabricated using a gel-casting method and observed with optical and scanning electron microscopes. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), wettability, and degradation tests were conducted. The highest content of TCP without W in the composition caused the highest hydrophilicity (water contact angle of 61.9 ± 6.3°), the fastest degradation rate (7% mass loss within 28 days), moderate ability to precipitate CaP after incubation in PBS, and no cytotoxicity for L929 cells. The highest content of W without TCP caused the highest hydrophobicity (water contact angle of 83.4 ± 1.7°), the lowest thermal stability, slower degradation (3% mass loss within 28 days), and did not evoke CaP precipitation. Moreover, some signs of cytotoxicity on day 1 were observed. The samples with both TCP and W showed moderate properties and the best cytocompatibility on day 4. Interestingly, they were covered with typical cauliflower-like hydroxyapatite deposits after incubation in phosphate-buffered saline (PBS), which might be a sign of their excellent bioactivity. [ABSTRACT FROM AUTHOR]

Background: Tissue engineering represents a promising field in regenerative medicine, with bioresorbable polymers such as polycaprolactone (PCL) playing a crucial role as scaffolds. These scaffolds support the growth and repair of tissues by mimicking the extracellular matrix. Objective: This study aimed to assess the in vivo performance of three-dimensional PCL scaffolds by evaluating their effects on bone repair in rat calvaria and the tissue reaction in subcutaneous implant sites, as well as their impact on major organs such as the kidneys, lungs, and liver. Methods: Three-dimensional scaffolds made of PCL were implanted in the subcutaneous tissue of rats' backs and calvaria. Histological analyses were conducted to observe the bone repair process in calvaria and the tissue response in subcutaneous implant sites. Additionally, the kidneys, lungs, and livers of the animals were examined for any adverse tissue alterations. Results: The histological analysis of the bone repair in calvaria revealed newly formed bone growing towards the center of the defects. In subcutaneous tissues, a thin fibrous capsule with collagenous fibers enveloping the implant was observed in all animals, indicating a positive tissue response. Importantly, no harmful alterations or signs of inflammation, hyperplasia, metaplasia, dysplasia, or hemorrhage were detected in the kidneys, lungs, and liver. Conclusions: The findings demonstrate that PCL scaffolds produced through additive manufacturing are biocompatible, non-cytotoxic, and bioresorbable, promoting osteoconduction without adverse effects on major organs. Hence, PCL is confirmed as a suitable biomaterial for further studies in tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the chondrogenic potential of chondrocyte transplants cultured in vitro on polyethersulfone (PES) membranes. Forty-eight rabbits (96 knee joints) were used in the project. The synthetic, macro-porous PES membranes were used as scaffolds. Fragments of articular cartilage were harvested from non-weight-bearing areas of the joints of the animals. Chondrocytes were isolated and then cultivated on PES scaffolds for 3 weeks. The animals were divided into four groups. All the lesions in the articular cartilage were full thickness defects. In Group I, autogenic chondrocytes on PES membranes were transplanted into the defect area; in Group II, allogenic chondrocytes on PES membranes were transplanted into the defect area; in Group III, pure PES membranes were transplanted into the defect area; and in Group IV, lesions were left untreated. Half of the animals from each group were terminated after 8 weeks, and the remaining half were terminated 12 weeks postoperatively. The samples underwent macroscopic evaluation using the Brittberg scale and microscopic evaluation using the O'Driscoll scale. The best regeneration was observed in Groups II and I. In Group I, the results were achieved with two surgeries, while in Group II, only one operation was needed. This indicates that allogenic chondrocytes do not require two surgeries, highlighting the importance of further in vivo studies to better understand this advantage. The success of the study and the desired properties of PES scaffolds are attributed mainly to the presence of sulfonic groups in the structure of the material. These groups, similar to chondroitin sulfate, which naturally occurs in hyaline cartilage, likely enable mutual affinity between the scaffold and cells and promote scaffold colonization by the cells. [ABSTRACT FROM AUTHOR]

The periodontium is a complex hierarchical structure composed of alveolar bone, periodontal ligament, cementum, and gingiva. Periodontitis is an inflammatory disease that damages and destroys the periodontal tissues supporting the tooth. Periodontal therapies aim to regenerate the lost tissues, yet current treatments lack the integration of multiple structural/biochemical instructive cues to induce a coordinated regeneration, which leads to limited clinical outcomes. Hierarchical biomaterial scaffolds offer the opportunity to recreate the organization and architecture of the periodontium with distinct compartments, providing structural biomimicry that facilitates periodontal regeneration. Various scaffolds have been fabricated and tested preclinically, showing positive regenerative results. This review provides an overview of the recent research on hierarchical scaffolds for periodontal tissue engineering (TE). First, the hierarchical structure of the periodontium is described, covering the limitations of the current treatments used for periodontal regeneration and presenting alternative therapeutic strategies, including scaffolds and biochemical factors. Recent research regarding hierarchical scaffolds is highlighted and discussed, in particular, the scaffold composition, fabrication methods, and results from in vitro/in vivo studies are summarized. Finally, current challenges associated with the application of hierarchical scaffolds for periodontal TE are debated and future research directions are proposed. [ABSTRACT FROM AUTHOR]

The assembly of peptide and peptide‐inspired building blocks into functional, well‐defined, multi‐length scale materials represents an exciting, rapidly expanding research field that bridges the principles of polymer science and engineering with a tremendous breadth of biomolecular interactions. The advantageous features of peptides, including their biocompatibility, functional diversity, and high purity, are complemented by the breadth of potential applications that may arise from their resultant structures and assemblies. Applications in biology (tissue scaffolding and drug conjugation), electronics (electron and/or ion‐conduction), and membranes (ion capture and ultrafiltration) represent a few of many examples where such biologically rich materials hold potential for enabling new routes to enhanced materials performance. Achieving successful solution and interfacial assembly techniques for peptides and other peptidomimetic materials requires obtaining a deep understanding of their design principles and limitations, as well as their amenability to structure formation when subjected to a variety of environmental conditions, such as pH, solvent, and temperature, to which such assembly methods may be exquisitely sensitive. This review especially focuses on mechanisms and the product of oligo‐ and polypeptide assembly, often resulting in the formation of extended, wire‐like structures obtained by solution methods, with inclusion of peptoid‐based structures and the complementary roles of polymerizations and step‐by‐step synthetic methods. Moreover, we describe relationships between naturally occurring peptide‐based structures, such as Geobacter pili, that in turn inspire self‐assembly of peptide‐based structures, composites with polymer materials, and assemblies therefrom. [ABSTRACT FROM AUTHOR]

Nerve injury can lead to defects in related motor functions. It is critical to achieve long‐term and convenient real‐time evaluation of motor function recovery status during nerve injury repair. In this study, an implantable PLLA/BTO piezoelectric sensor (PBPS) with good biodegradability and biocompatibility for real time evaluation of the motor function recovery after nerve injury is developed. PLLA fibers doped with BTO are employed as piezoelectric material in PBPS, which can convert the biomechanical signals generated by motion into electrical signals. PBPS can be implant simultaneously with commonly used tissue scaffolds for treatment in the rats with sciatic nerve injury. The linearity of the pressure and the output voltage of PBPS is ≈0.9445. For the evaluation effectiveness, as the treatment process progresses, the signals generated by PBPS exhibited good consistency with EMG signals, indicating effectively evaluation of the motor function. Moreover, the integration of PBPS and wireless module can break the limitations of time and space for sensing and realize wireless evaluation of motor function in rat. The implantable sensor based on PBPS may bring new ideas for the development of implantable bioelectronics. [ABSTRACT FROM AUTHOR]

Soft tissue engineering has focused on green, solvent-free biopolymers with rubber-like characteristics. One of the well-known elastomeric polyesters is polyglycerol sebacate (PGS). The present investigation involves the synthesis of a novel biopolymer composed of PGS-co-poly(ε-caprolactone) (PCL) copolymer, alongside hydroxyapatite (HA) using bovine bone. These synthesized materials were utilized to build scaffolds using 18–22 kV electrospinning. By in situ polymerization, PGS-co-PCL/HA nanocomposites with 5% and 10% hydroxyapatite nanoparticles were developed. Various analysis such as FTIR, TGA, SEM, and DSC were utilized to examine the prepared samples. Introducing 10% HA to the PGS-co-PCL copolymer blends boosted nanocomposite mechanical strength by 300%. Meanwhile, PGS-co-PCL-based samples and their nanocomposites demonstrated promising biocompatibility and antibacterial characteristics. Biodegradability experiments revealed that at pH 7, PGS-co-PCL-HA10% was degraded by 45% within 30 days, whereas at pH 11, degradation accelerated to 65%. This study's findings provide a novel approach for soft tissue engineers to construct effective scaffolds with great biocompatibility and enhanced mechanical properties by combining PGS with co-PCL and adding HA nanoparticles. [ABSTRACT FROM AUTHOR]

Recent advancements in tissue engineering have witnessed luffa-derived scaffolds, exhibiting their exceptional potential in cellular proliferation, biocompatibility, appropriate interconnectivity, and biomechanical strength. In vivo studies involved implanting fabricated scaffolds subcutaneously in Wistar rats to evaluate their impact on the heart, liver, and kidneys. This approach provided a safe and minimally invasive means to evaluate scaffold compatibility with surrounding tissues. Male Wistar rats were categorized into four distinct groups, Group A, B, C, and D are referred to as 3% LC implanted scaffolds, 5% LC implanted scaffolds, control (without luffa scaffolds), and Sham (without any scaffold implantation), respectively. Histological analysis in all the groups indicated that the animal models did not exhibit any signs of inflammation or toxicity, suggesting favorable tissue response to the implanted scaffolds. Initial observations revealed elevated levels of enzymes and biomarkers in the experimental groups after a 24 h interval, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatine kinase-MB (CK-MB), and serum creatinine. However, these parameters normalized 3 weeks post-implantation, with no significant increase compared to the control groups, suggesting that the implanted luffa-based scaffolds did not induce adverse effects on the heart, liver, and kidneys. Furthermore, the scaffold's significant pore size and porosity enable it to release drugs, including antibacterial medications. This study demonstrates promising results, indicating excellent scaffold porosity, sustained drug release, affirming the in vivo biocompatibility, absence of inflammatory responses, and overall tissue compatibility highlighting the immense potential of these luffa-based scaffolds in various tissue engineering and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

Extensive research efforts have been focused on customizing the microstructure, macrostructure, and phase composition of calcium phosphate for enhanced biocompatibility and bioactivity in scaffolds for bone substitutes. Despite significant progress, achieving precise phase composition and microstructure remains a challenge, primarily due to the necessity of scaffold sintering. This study addresses the challenges in developing customized patient‐specific bone substitutes by proposing a sequential approach that reduces processing steps while providing control over the phase and morphology of the scaffolds’ structure. The methodology utilizes freeze‐casting and sintering for highly porous the scaffolds’ preparation, followed by hydrothermal treatment to modify the microstructure. The introduction of CaCO3 induces a phase transformation of tricalcium phosphate, increasing the hydroxyapatite content, while the overall macrostructure retains the characteristics of freeze‐casting. The surface morphology undergoes a transition from equiaxial grains to whiskers‐like structures and hexagonal rods, impacting compressive strength. Following hydrothermal treatment, the formation of whiskers‐like hydroxyapatite grains leads to a notable strength increase from 2.8 to 5.7 MPa. Remarkably, the scaffolds undergo nearly complete phase transformation, shifting from 100% tricalcium phosphate to 99% hydroxyapatite, all while conserving the macrostructure. [ABSTRACT FROM AUTHOR]

Traditional metallic biomaterials including titanium and its alloys, stainless steel, cobalt‐chromium alloys, magnesium alloys are gold standards for load bearing hard tissue applications, because of adequate mechanical properties such as elastic modulus, ductility and strength for long term support and stability. However, metallic implants suffer from poor osteointegration and early degradation in host body, owing to an array of factors which include stress shieling effect, corrosion, metal toxicity, microbial contamination and low bioactivity. Therefore, to improve integration of implants with host tissue and overall mechanical and biological functions, metallic implants are coated with bioactive glasses (BG). BG are one of the most promising implant coating materials used for bone repair and reconstruction, mainly because of excellent angiogenic, osteoconductive, osteoinductive, corrosion resistance, resorbability, biocompatibility, bioactivity and anti‐microbial properties. Various BG compositions are employed for diverse biomedical applications ranging from wound healing, bone formation, corrosion resistance, drug delivery to scaffolds in tissue engineering and different methods are used for coating BG on implants to enhance stability and bond strength between implant and coating. This narrative review gives a detailed overview on metallic implants, issues of metal alloys when used in implants and how metallic implants are improved by various BG compositions and coating methods. This review provides an updated information on advantages of different BG compositions in implants fabrication in order to address challenges and tailor mechanical and biological properties of implants for future applications. [ABSTRACT FROM AUTHOR]

In this study, the aim is to investigate the effect of engineering the cell size and porosity of 3D‐printed poly lactic acid (PLA) porous scaffolds from the Kelvin model for bone tissue engineering applications. The Kelvin model is used as a bone tissue scaffold with different cell sizes and porosities. PLA, as a biodegradable and biocompatible polymer, is used to fabricate these scaffolds using the FDM technique. A compression test is used to evaluate the mechanical properties of scaffolds. The MTT assay has been used to investigate cell viability. For osteogenic differentiation studies, ALP activity and ARS assays are used. Increasing the porosity reduces the mechanical properties of the scaffold. While increasing the cell size at constant porosity increases the Young's modulus and yield stress in the samples, it is also observed that, in high porosities, the increase in cell size weakens the mechanical properties. Also, Kelvin model scaffolds help the proliferation and osteogenic differentiation of cells and have no toxic effect. It is demonstrated that this approach promotes the effectiveness of the Kelvin architecture for bone tissue engineering. As a result, designing the most suitable model based on cell size and porosity for the treatment process in the targeted area could be promising. [ABSTRACT FROM AUTHOR]

Polycaprolactone (PCL) is a pivotal biopolymer in biomedicine, especially in tissue engineering for scaffolds and biomaterials. Recognized for its effectiveness as a drug carrier with superior controlled release properties, PCL is commonly processed via electrospinning, typically employing chlorinated or fluorinated solvents known for cellular toxicity. As an environmentally conscious alternative, this study explores glacial acetic acid (AA) as a solvent for electrospinning solutions. Investigating PCL's molecular degradation through acid hydrolysis in acidic solvents (AA/formic acid) (FA), the study assesses the impact of storage time on resulting structures. Solutions containing 30% PCL in AA/FA (9:1) were stored at 35°C for up to 14 days, revealing a 50% molar mass reduction during solubilization through gel permeation chromatography, x‐ray diffraction, and Fourier‐transform infrared analyses. This reduction influenced chain packing, raising crystallinity indices from approximately 37% to 49% with prolonged storage. The reduced molar mass resulted in unstable Taylor cones, generating diverse mat morphologies. Intriguingly, this degradation enhanced water adsorption capacity, indicating exposed hydrogen bonds from acid hydrolysis as an advantageous trait for regenerative medicine. This underscores the hydrolyzed materials' potential for cell anchoring in tissue engineering. [ABSTRACT FROM AUTHOR]