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Biomaterials play an important role in treating bone defects. The functional characteristics of scaffolds, such as their structure, mechanical strength, and antibacterial and osteogenesis activities, effectively promote bone regeneration. In this study, mineralized collagen and polycaprolactone were used to prepare loaded porous scaffolds with bilayer-structured microspheres with dual antibacterial and osteogenesis functions. The different drug release mechanisms of PLGA and chitosan in PLGA/CS microspheres caused differences in the drug release models in terms of the duration and rate of Pac-525 and BMP-2 release. The prepared PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffolds were analyzed in terms of physical characteristics, bioactivity, and antibacterial properties. The scaffolds with a dimensional porous structure showed similar porosity and pore diameter to cancellous bone. The release curve of the microspheres and scaffolds with high encapsulation rates displayed the two-stage release of Pac-525 and BMP-2 over 30 days. It was found that the scaffolds could inhibit S. aureus and E. coli and then promote ALP activity. The PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffold could be used as a dual delivery system to promote bone regeneration. [ABSTRACT FROM AUTHOR]

Alginates are salts of alginic acid derived mainly from sea algae of the genus brown algae. They are also synthesized by some bacteria. They belong to negatively charged polysaccharides exhibiting some rheological properties. High plasticity and the ability to modify the structure are the reasons for their application in numerous industries. Moreover, when in contact with the living tissue, they do not trigger an immune response, and for this reason they are the most often tested materials for medical applications. The paper discusses the latest applications, including 3D bioprinting, drug delivery systems, and sorptive properties. Recognizing alginates as biomaterials, it emphasizes the necessity for precise processing and modification to industrialize them for specific uses. This review aims to provide a thorough understanding of the advancements in alginate research, underscoring their potential for innovative applications. [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]

Severe injuries to skeletal muscles, including cases of volumetric muscle loss (VML), are linked to substantial tissue damage, resulting in functional impairment and lasting disability. While skeletal muscle can regenerate following minor damage, extensive tissue loss in VML disrupts the natural regenerative capacity of the affected muscle tissue. Existing clinical approaches for VML, such as soft-tissue reconstruction and advanced bracing methods, need to be revised to restore tissue function and are associated with limitations in tissue availability and donor-site complications. Advancements in tissue engineering (TE), particularly in scaffold design and the delivery of cells and growth factors, show promising potential for regenerating damaged skeletal muscle tissue and restoring function. This article provides a brief overview of the pathophysiology of VML and critiques the shortcomings of current treatments. The subsequent section focuses on the criteria for designing TE scaffolds, offering insights into various natural and synthetic biomaterials and cell types for effectively regenerating skeletal muscle. We also review multiple TE strategies involving both acellular and cellular scaffolds to encourage the development and maturation of muscle tissue and facilitate integration, vascularization, and innervation. Finally, the article explores technical challenges hindering successful translation into clinical applications. [ABSTRACT FROM AUTHOR]

Proteins are one of the most prevalent components of the extracellular matrix, which are used in bone tissue engineering for construction of scaffolds. Due to their biocompatibility, biodegradability, non-immunogenicity and having cell motifs (cell recognition sites), they are capable of providing cell adhesion and favorable scaffold-cell interactions. However, proteins have crucial disadvantages, including lack of mechanical strength required for bone regeneration, as well as rapid degradation rate, which have restricted their implementation as a sole component in the construction of scaffolds. To overcome such disadvantages and at the same time, benefit from their properties, proteins are combined with other materials, such as carbohydrates and synthetic polymers and glass-ceramides. This review summarizes different types of protein hybrid scaffolds for bone tissue engineering and also discusses the function and significance of proteins in bone regeneration. [ABSTRACT FROM AUTHOR]

The biochemical and physical properties of a scaffold can be tailored to elicit specific cellular responses. However, it is challenging to decouple their individual effects on cell‐material interactions. Here, we solvent‐cast 3D printed different ratios of high and low molecular weight (MW) poly(caprolactone) (PCL) to fabricate scaffolds with significantly different stiffnesses without affecting other properties. Ink viscosity was used to match processing conditions between inks and generate scaffolds with the same surface chemistry, crystallinity, filament diameter, and architecture. Increasing the ratio of low MW PCL resulted in a significant decrease in modulus. Scaffold modulus did not affect human mesenchymal stromal cell (hMSC) differentiation under osteogenic conditions. However, hMSC response was significantly affected by scaffold stiffness in chondrogenic media. Low stiffness promoted more stable chondrogenesis whereas high stiffness drove hMSC progression toward hypertrophy. These data illustrate how this versatile platform can be used to independently modify biochemical and physical cues in a single scaffold to synergistically enhance desired cellular response. [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]

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]

Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuliresponsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials. [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]

Skin is the largest protective tissue of the body and is at risk of damage. Hence, the design and development of wound dressing materials is key for tissue repair and regeneration. Although silk fibroin is a known biopolymer in tissue engineering, its degradation rate is not correlated with wound closure rate. To address this disadvantage, we mimicked the hierarchical structure of skin and also provided antibacterial properties; a hydrogel with globular structure consisting of silk fibroin, pluronic F127, and curcumin was developed. In this regard, the effect of pluronic and curcumin on the structural and mechanical properties of the hydrogel was studied. The results showed that curcumin affected the particle size, crystallinity, and ultimate elongation of the hydrogels. In vitro assays confirmed that the hydrogel containing curcumin is not cytotoxic while the diffused curcumin and pluronic provided a considerable bactericidal property against Methicillin-resistant Staphylococcus aureus. Interestingly, presence of pluronic caused more than a 99% reduction in planktonic and adherent bacteria in the curcumin-free hydrogel groups. Moreover, curcumin improved this number further and inhibited bacteria adhesion to prevent biofilm formation. Overall, the developed hydrogel showed the potential to be used for skin tissue regeneration. [ABSTRACT FROM AUTHOR]

Cultivated meat, an advancement in cellular agriculture, holds promise in addressing environmental, ethical, and health challenges associated with traditional meat production. Utilizing tissue engineering principles, cultivated meat production employs biomaterials and technologies to create cell-based structures by introducing cells into a biocompatible scaffold, mimicking tissue organization. Among the cell sources used for producing muscle-like tissue for cultivated meats, primary adult stem cells like muscle satellite cells exhibit robust capabilities for proliferation and differentiation into myocytes, presenting a promising avenue for cultivated meat production. Evolutionarily optimized for growth in a 3D microenvironment, these cells benefit from the biochemical and biophysical cues provided by the extracellular matrix (ECM), regulating cell organization, interactions, and behavior. While plant protein-based scaffolds have been explored for their utilization for cultivated meat, they lack the biological cues for animal cells unless functionalized. Conversely, a decellularized bovine placental tissue ECM, processed from discarded birth tissue, achieves the biological functionalities of animal tissue ECM without harming animals. In this study, collagen and total ECM were prepared from decellularized bovine placental tissues. The collagen content was determined to be approximately 70% and 40% in isolated collagen and ECM, respectively. The resulting porous scaffolds, crosslinked through a dehydrothermal (DHT) crosslinking method without chemical crosslinking agents, supported the growth of bovine myoblasts. ECM scaffolds exhibited superior compatibility and stability compared to collagen scaffolds. In an attempt to make cultivate meat constructs, bovine myoblasts were cultured in steak-shaped ECM scaffolds for about 50 days. The resulting construct not only resembled muscle tissues but also displayed high cellularity with indications of myogenic differentiation. Furthermore, the meat constructs were cookable and able to sustain the grilling/frying. Our study is the first to utilize a unique bovine placentome-derived ECM scaffold to create a muscle tissue-like meat construct, demonstrating a promising and sustainable option for cultivated meat production. [ABSTRACT FROM AUTHOR]

Simple Summary: Tendon injuries are known to be difficult to heal, making effective treatments crucial. This study examines the potential of stem cells derived from sheep fat tissue for tendon repair, since little information is available on their tenogenic potential. The focus of this study was to understand how these stem cells can be induced to develop into tendon cells. Initially, the cells were grown in the lab to ensure that their essential properties were maintained. Two methods were then employed to promote the acquisition of tendon-like characteristics: exposing the cells to a tenogenic conditioned medium or seeding them on a scaffold that mimics a tendon structure. The results indicated that these stem cells could be expanded without aging or changes in their characteristics. When exposed to the tendon medium, the cells were able to start the tendon differentiation process but were not able to complete it. Conversely, when seeded on the scaffold, the cells changed their naïve genetic and protein profile and acquired that of the typical tendon cells. This suggests that these stem cells can be addressed towards tendon cells, being more effective when seeded on a tendon biomimetic scaffold. These findings highlight the potential use of these stem cell treatments for tendon injuries, particularly in veterinary medicine. Adipose-derived stem cells (ADSCs) hold promise for tendon repair, even if their tenogenic plasticity and underlying mechanisms remain only partially understood, particularly in cells derived from the ovine animal model. This study aimed to characterize oADSCs during in vitro expansion to validate their phenotypic properties pre-transplantation. Moreover, their tenogenic potential was assessed using two in vitro-validated approaches: (1) teno-inductive conditioned media (CM) derived from a co-culture between ovine amniotic stem cells and fetal tendon explants, and (2) short- (48 h) and long-term (14 days) seeding on highly aligned PLGA (ha-PLGA) electrospun scaffold. Our findings indicate that oADSCs can be expanded without senescence and can maintain the expression of stemness (Sox2, Oct4, Nanog) and mesenchymal (CD29, CD166, CD44, CD90) markers while remaining negative for hematopoietic (CD31, CD45) and MHC-II antigens. Of note, oADSCs' tendon differentiation potential greatly depended on the in vitro strategy. oADSCs exposed to CM significantly upregulated tendon-related genes (COL1, TNMD, THBS4) but failed to accumulate TNMD protein at 14 days of culture. Conversely, oADSCs seeded on ha-PLGA fleeces quickly upregulated the tendon-related genes (48 h) and in 14 days accumulated high levels of the TNMD protein into the cytoplasm of ADSCs, displaying a tenocyte-like morphology. This mechano-sensing cellular response involved a complete SOX9 downregulation accompanied by YAP activation, highlighting the efficacy of biophysical stimuli in promoting tenogenic differentiation. These findings underscore oADSCs' long-term self-renewal and tendon differentiative potential, thus opening their use in a preclinical setting to develop innovative stem cell-based and tissue engineering protocols for tendon regeneration, applied to the veterinary field. [ABSTRACT FROM AUTHOR]

Osteocytes perceive and process mechanical stimuli in the lacuno-canalicular network in bone. As a result, they secrete signaling molecules that mediate bone formation and resorption. To date, few three-dimensional (3D) models exist to study the response of mature osteocytes to biophysical stimuli that mimic fluid shear stress and substrate strain in a mineralized, biomimetic bone-like environment. Here we established a biomimetic 3D bone model by utilizing a state-of-art perfusion bioreactor platform where immortomouse/Dmp1-GFP-derived osteoblastic IDG-SW3 cells were differentiated into mature osteocytes. We evaluated proliferation and differentiation properties of the cells on 3D microporous scaffolds of decellularized bone (dBone), poly(L-lactide-co-trimethylene carbonate) lactide (LTMC), and beta-tricalcium phosphate (β-TCP) under physiological fluid flow conditions over 21 days. Osteocyte viability and proliferation were similar on the scaffolds with equal distribution of IDG-SW3 cells on dBone and LTMC scaffolds. After seven days, the differentiation marker alkaline phosphatase (Alpl), dentin matrix acidic phosphoprotein 1 (Dmp1), and sclerostin (Sost) were significantly upregulated in IDG-SW3 cells (p = 0.05) on LTMC scaffolds under fluid flow conditions at 1.7 ml/min, indicating rapid and efficient maturation into osteocytes. Osteocytes responded by inducing the mechanoresponsive genes FBJ osteosarcoma oncogene (Fos) and prostaglandin-endoperoxide synthase 2 (Ptgs2) under perfusion and dynamic compressive loading at 1 Hz with 5 % strain. Together, we successfully created a 3D biomimetic platform as a robust tool to evaluate osteocyte differentiation and mechanobiology in vitro while recapitulating in vivo mechanical cues such as fluid flow within the lacuno-canalicular network. This study highlights the importance of creating a three-dimensional (3D) in vitro model to study osteocyte differentiation and mechanobiology, as cellular functions are limited in two-dimensional (2D) models lacking in vivo tissue organization. By using a perfusion bioreactor platform, physiological conditions of fluid flow and compressive loading were mimicked to which osteocytes are exposed in vivo. Microporous poly(L-lactide-co-trimethylene carbonate) lactide (LTMC) scaffolds in 3D are identified as a valuable tool to create a favorable environment for osteocyte differentiation and to enable mechanical stimulation of osteocytes by perfusion and compressive loading. The LTMC platform imitates the mechanical bone environment of osteocytes, allowing the analysis of the interaction with other cell types in bone under in vivo biophysical stimuli. [Display omitted] [ABSTRACT FROM AUTHOR]

Regenerative therapy, a key area of tissue engineering, holds promise for restoring damaged organs, especially in bone regeneration. Bone healing is natural to the body but becomes complex under stress and disease. Large bone deformities pose significant challenges in tissue engineering. Among various methods, scaffolds are attractive as they provide structural support and essential nutrients for cell adhesion and growth. Collagen and hydroxyapatite (HA) are widely used due to their biocompatibility and biodegradability. Collagen and nano-scale HA enhance cell adhesion and development. Thus, nano HA/collagen scaffolds offer potential solutions for bone regeneration. This review focuses on the use and production of nano-sized HA/collagen composites in bone regeneration. Article Highlights Current treatment options for bone trauma The skeletal system's structure, consisting of cortical and trabecular bone, is vital for mobility, support, protection, blood cell distribution, nutrient regulation and endocrine function. High-impact incidents, such as vehicle collisions and falls, are primary causes of bone deformities and trauma, leading to significant economic, psychological and social burdens. Large segmental bone abnormalities are mainly treated through surgical procedures like vascularized bone transplantation and bone transfer, with treatment outcomes influenced by various patient-specific factors. Ideal bone transplants should be osteoinductive, osteoconductive, osteogenic, readily available and cost-effective, with autografts being the most superior option due to their high efficacy and low risk of immune reaction. Allografts, derived from the same species, are treated to mitigate immunogenic response and infection risks, available in forms such as intact segments, cortical-spongy segments, bone chips, powder and demineralized bone matrices. Xenografts, particularly from bovine sources, provide a porous hydroxyapatite-based structure that supports mechanical reinforcement, osteoconduction and angiogenesis, commonly used in maxillary sinus floor elevation treatments. Emergence of scaffolds in bone regeneration Scaffolds play a crucial role in supporting tissue repair and regeneration, facilitating cellular deposition and morphogenic signals essential for bone regeneration in conditions like osteoporosis and bone malignancies. Exploration of biomaterials such as bioactive glass and calcium phosphate cements reveals promising outcomes, with bioactive glass demonstrating superior remodeling capabilities over autogenous bone and injectable cements providing customizable defect filling in procedures like cranioplasty. Surface characteristics, including chemistry, topography and roughness, profoundly influence scaffold integration and cellular behavior, impacting bone-forming cell adhesion, proliferation and protein binding essential for effective bone regeneration. Pore size is a critical parameter in scaffold design, with larger pores (>300 μm) favored for bone ingrowth, although optimal bone regeneration may vary with pore size, highlighting the complex connection between pore size, bone growth and scaffold strength. Biomaterial diversity, ranging from natural polymers like chitosan and collagen to synthetic polymers such as PCL, PLA, or PLGA, offers a variety of biodegradable options tailored for bone tissue engineering applications. Role of collagen in bone regeneration Natural biopolymers, such as collagen, are gaining attention in bone regeneration due to their resemblance to native extracellular matrix (ECM) components, reducing the risk of immunological reactions and facilitating tissue regeneration. Collagen, a predominant structural protein in vertebrates, regulates crucial biological processes like cell attachment, migration and differentiation, making it a promising candidate for scaffolds in bone tissue engineering. Despite collagen's favorable biological properties, its mechanical weaknesses hinder widespread utilization, prompting research into enhancing its durability through crosslinking methods. Chemical and physical crosslinking agents, such as choline-based salts, have been explored to strengthen collagen scaffolds, improving their stability and mechanical properties. Incorporating bio-ceramics like HA into collagen matrices can further enhance scaffold strength while maintaining porosity, offering significant potential for advancing bone tissue engineering applications. Hydroxyapatite in bone regeneration Hydroxyapatite (HA), a key component of bone composition, exhibits a complex crystal arrangement with uniform orientation of hydroxyl groups, contributing to its structural integrity and biocompatibility. HA, comprising approximately 20% of bone composition, possesses chemical elements analogous to vertebrate hard tissues, making it a biodegradable biomaterial with significant potential in orthopedics and maxillofacial surgery. The mechanical properties of HA can be tailored through synthesis methods like sintering, influencing its durability and in vivo biodegradability, with lower sintering temperatures enhancing biodegradability while compromising mechanical strength. Recent advancements in artificial bone grafts have focused on HA-based materials, either pure or in composites, due to their biocompatibility, biomineralization capabilities and porous interlinked structure, essential for osteoconduction and osteointegration. Utilization of collagen/HA composites in bone related ailments Collagen/HA composites offer synergistic osteoconductive effects, making them ideal for bone regeneration applications, with potential enhancements through additional active ingredients. Various fabrication techniques such as gel casting, compacting and computer-assisted rapid prototyping enable precise control over the mechanical and biological properties of collagen/HA scaffolds, enhancing their suitability for tissue engineering. The mechanical properties of collagen scaffolds are augmented by HA incorporation, with factors like particle size influencing cellular adhesion and proliferation, demonstrating enhanced osteogenic potential compared with pure collagen scaffolds. Synthesis methods for HA/collagen composites, including co-precipitation and direct blending, yield hierarchical structures resembling natural bone, with potential enhancements through the incorporation of growth factors or biologically active substances. Porosity plays a significant role in the biological characteristics of HA/collagen composites, with increased porosity facilitating cell migration, vascularization and mechanical adaptability, despite potential reductions in mechanical strength. HA/collagen scaffolds can be utilized for drug delivery in bone-related disorders, enabling sustained release of therapeutic agents to target specific sites, with potential applications in tumor inhibition and antimicrobial treatment, offering a promising avenue for personalized medicine in bone therapeutics. Future perspective Collagen and HA ceramics offer strong biocompatibility, tailored mechanical strength and osteoconductivity for bone regeneration. Ongoing research integrates bioactive compounds into HA/collagen hybrids to enhance osteoinductivity and pharmacological intervention in bone pathologies. Nano-HA promotes osteoblast adhesion and bone regeneration, enhancing scaffold effectiveness. Collagen scaffolds, though prone to degradation, are being optimized for stability and controlled degradation, ensuring suitability for bone regeneration. Advanced fabrication techniques like 3D printing aim to improve scaffold mechanical properties and drug delivery capabilities, advancing treatment effectiveness. Multifunctional composites, combining growth stimulants and antibiotics in HA/collagen scaffolds, show promise for tailored therapeutic approaches, enhancing treatment outcomes in bone defects and pathologies. [ABSTRACT FROM AUTHOR]

Two‐photon lithography is considered a promising technology because it can achieve high resolution up to scale of 100 nm among additional processing technologies; further, it can be used to fabricate nano‐/microstructures. However, it requires an unrealistic long time to obtain a practical model that is close to the human organ diameter in the order of millimeters. In this study, an in‐process‐resolution‐tunable (iPRT) stereolithography system is reported, that realizes an optimal laser processing pathway using a new algorithm that automatically generates the processing pathway obtained by dividing the fabrication area by the effect of microstructure disappearance during the surface offset. It is demonstrated that the aforementioned algorithm can produce structures up to 50 times faster than the conventional methods and can be applied to cell culture scaffold for regenerative medicine. [ABSTRACT FROM AUTHOR]

Advanced periodontitis poses a significant threat to oral health, causing extensive damage and loss of both hard and soft periodontal tissues. While traditional therapies such as scaling and root planing can effectively halt the disease's progression, they often fail to fully restore the original architecture and function of periodontal tissues due to the limited capacity for spontaneous regeneration. To address this challenge, periodontal tissue engineering has emerged as a promising approach. This technology centers on the utilization of biomaterial scaffolds, which function as three-dimensional (3D) templates or frameworks, supporting and guiding the regeneration of periodontal tissues, including the periodontal ligament, cementum, alveolar bone, and gingival tissue. These scaffolds mimic the extracellular matrix (ECM) of native periodontal tissues, aiming to foster cell attachment, proliferation, differentiation, and, ultimately, the formation of new, functional periodontal structures. Despite the inherent challenges associated with preclinical testing, the intensification of research on biomaterial scaffolds, coupled with the continuous advancement of fabrication technology, leads us to anticipate a significant expansion in their application for periodontal tissue regeneration. This review comprehensively covers the recent advancements in biomaterial scaffolds engineered specifically for periodontal tissue regeneration, aiming to provide insights into the current state of the field and potential directions for future research. [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]

This review discusses recent studies on the combination of nanoparticles (NPs) and biomaterials for the treatment of chronic wounds, especially diabetic foot ulcers (DFUs). This article provides a concise overview of several types of NPs. We will discuss how these NPs possess inherent characteristics that enhance the bioactivity, mechanical strength, tissue adhesion, and antibacterial properties of wound repairing scaffolds. Additionally, we explore their capacity to carry active substances and genes to the wound site. In this context, a comprehensive elucidation of various notable complexities associated with wound repair is provided, alongside corresponding strategies to mitigate them. So that, the adoption of NPs within wound dressings is advocated as a proficient technological approach to address each of these challenges. Furthermore, this article examines several physical and chemical techniques employed by researchers for the incorporation of NPs into scaffolds. [ABSTRACT FROM AUTHOR]

Ex vivo follicle growth is an essential tool, enabling interrogation of folliculogenesis, ovulation, and luteinization. Though significant advancements have been made, existing follicle culture strategies can be technically challenging and laborious. In this study, we advanced the field through development of a custom agarose micromold, which enables scaffold-free follicle culture. We established an accessible and economical manufacturing method using 3D printing and silicone molding that generates biocompatible hydrogel molds without the risk of cytotoxicity from leachates. Each mold supports simultaneous culture of multiple multilayer secondary follicles in a single focal plane, allowing for constant timelapse monitoring and automated analysis. Mouse follicles cultured using this novel system exhibit significantly improved growth and ovulation outcomes with comparable survival, oocyte maturation, and hormone production profiles as established three-dimensional encapsulated in vitro follicle growth (eIVFG) systems. Additionally, follicles recapitulated aspects of in vivo ovulation physiology with respect to their architecture and spatial polarization, which has not been observed in eIVFG systems. This system offers simplicity, scalability, integration with morphokinetic analyses of follicle growth and ovulation, and compatibility with existing microphysiological platforms. This culture strategy has implications for fundamental follicle biology, fertility preservation strategies, reproductive toxicology, and contraceptive drug discovery. [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]

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]

In this work, we numerically study the hydrodynamic permeability of new-generation artificial porous materials used as scaffolds for cell growth in a perfusion bioreactor. We consider two popular solid matrix designs based on triply periodic minimal surfaces, the Schwarz P (primitive) and D (diamond) surfaces, which enable the creation of materials with controlled porosity gradients. The latter property is crucial for regulating the shear stress field in the pores of the scaffold, which makes it possible to control the intensity of cell growth. The permeability of functionally graded materials is studied within the framework of both a microscopic approach based on the Navier-Stokes equation and an averaged description of the liquid filtration through a porous medium based on the equations of the Darcy or Forchheimer models. We calculate the permeability coefficients for both types of solid matrices formed by Schwarz surfaces, study their properties concerning forward and reverse fluid flows, and determine the ranges of Reynolds number for which the description within the Darcy or Forchheimer model is applicable. Finally, we obtain a shear stress field that varies along the sample, demonstrating the ability to tune spatially the rate of tissue growth. [ABSTRACT FROM AUTHOR]

Abstract 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. Graphical abstract

Freeze casting is an effective way to fabricate the porous ceramics with anisotropic and interconnected porous structures and can be used in various applications, such as filtration, adsorption, and insulation. However, the ceramic‐based scaffolds fabricated by freeze casting have the upper limit of porosity since excessively low solid content in the slurry will lead to structural instability and cracks formation in scaffolds. This study aims at combining the freeze casting and sol–gel method and developing a hybrid process to overcome the limitation of freeze casting. Besides, the effects of solid content and cooling rates on the microstructure of ultralightweight alumina scaffolds (ULASs) and their mechanical and thermal properties were investigated. Aluminum isopropoxide was selected as the precursor to conduct the hydrolysis reaction in acid environment and condensation process by heat treatment. The successfully synthesized alumina scaffolds have ultrahigh porosity (>90%), low bulk density (0.1240–0.2429 g/cm3), and low relative density (0.0314–0.0615). The anisotropic porous lamellar structure was evaluated by scanning electron microscope, µ‐CT, and mercury porosimeter. A lot of nanoscale pores are observed on the lamellae surfaces, forming the dual‐scale porous structure inside the scaffolds and contributing to higher specific surface area. The unique anisotropic structure, high porosity, and stable mechanical properties enable ULASs to deliver a low thermal conductivity of 0.2 W/m/K and large anisotropy in thermal properties, possessing great potential for thermal insulative materials. This sol–gel/freeze‐casting hybrid approach is believed to be extended to different material systems and provide promising potentials in fabricating the porous materials with various functionalities. [ABSTRACT FROM AUTHOR]

Cartilage damage and degeneration pose significant challenges in orthopedic medicine, innovative approaches for regenerative therapies. The hydrogel is designed to provide a supportive matrix for cell growth and differentiation while delivering therapeutic agents to promote tissue repair. Drug-loaded hydrogels have been extensively studied for cartilage regenerative medicine, offering promising results for tissue engineering and drug delivery applications. These hydrogels, composed of homopolymers and copolymers, can absorb water and create an appropriate microenvironment similar to the extracellular matrix (ECM). Various polymers and crosslinking methods are explored to optimize the hydrogel's mechanical properties, biocompatibility, and drug release kinetics. Additionally, the study investigates the efficacy of different drugs, growth factors, and bioactive molecules for enhancing chondrogenesis and cartilage regeneration within the hydrogel scaffold. The developed drug-loaded hydrogel holds great promise for addressing the unmet clinical need for effective cartilage regenerative therapies, offering potential advancements in orthopedic medicine. [ABSTRACT FROM AUTHOR]

Melt electrowriting (MEW) has become a novel technique for textile (scaffold) biomanufacturing of Tissue Engineering scaffolds which, once they are combined with cells, we refer to them as biotextiles. The accuracy of weaving resorbable polymer fibers provides paradigmatic advances over electrospinning. This innovation in MEW allows control of pore geometry, mechanical properties, and overall geometries, especially the ability to bring two thin membranes formed from different, complementary types of cells as occurs in the key areas of most tissues. The biofabrication of large surfaces (i.e., high surface areas) where two or more types of cells are in very thin membranes in direct contact is unprecedented. One of the main challenges is to learn how to tame the MEW process parameters to biomanufacture personalized textiles with geometries other than the scaffolds produced with the well-demonstrated flat sheet and straight tube collectors. Why? Because no tissue within the human body takes the form of a flat sheet or straight tube. In this work, we show the challenges involved in translating MEW to the printing of textiles with out-of-plane geometries and validated a promising multi-axis kinematic strategy to orthogonally aligned the printing nozzle to them. Of particular interest to us is the effect of the fiber collector geometry on the electric field (i.e., inhomogeneities not seen with flat sheet and straight tube collectors) and thus in fiber deposition accuracy. The benefit of applying multi-axis CAM methodologies and the use of a digital twin to assist in MEW biomanufacturing is also validated. We believe these advances will unleash the imagination of people working with MEW for novel applications in Regenerative Medicine. [ABSTRACT FROM AUTHOR]

Highlights This review provides a comprehensive summary associated with recent progress in the preparation and application of microgels. The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy. This review expounds on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering. Through stimulating innovative ideas, the present review paves new avenues for expanding the application of microgels in cell delivery techniques.