Biomaterial Scaffolds Research Articles

Dual delivery of metformin and Y15 from a PLGA scaffold for the treatment of platinum-resistant ovarian cancer.

Drug-loaded poly(lactic-co-glycolic acid) (PLGA) scaffolds were fabricated using a mold-less technique to investigate whether the combined delivery of both Y15 (FAK inhibitor) and metformin would result in enhanced effects on cell viability compared to the release of each drug alone for the treatment of platinum-resistant ovarian cancer (PROC). Scaffolds were fabricated using an easy and economical mold-less technique that combined PLGA and the drugs (i.e. metformin and/or Y15) in tetraglycol and injected in PBS, to form a globular morphology. The exposure of cells to metformin and Y15 resulted in a significantly enhanced cytotoxic efficacy compared to single-drug treatment with either metformin or Y15. When the drugs were delivered using the PLGA scaffolds, the combination of the two drugs was significantly more cytotoxic compared to scaffolds containing metformin only and Y15 only. The combination of metformin and Y15 can result in an increase in antitumor activity in PROC cells through apoptosis. The delivery of both drugs from the PLGA biomaterial scaffold allowed for a more enhanced combinational effect compared to the utilization of free drugs (without a scaffold) and should be further explored as a promising treatment of PROC.

Design and optimization of tamarind seed polysaccharide-based scaffold for tissue engineering applications using statistical modeling and machine learning, and it's in-vitro validation.

This study explores the development and optimization of a novel biomaterial scaffold for tissue engineering, composed of Tamarind seed polysaccharide (TSP), Hydroxypropyl methylcellulose (HPMC), Chitosan (CS), and Sodium alginate (ALG). Scaffold properties, including swelling, degradation, porosity, mechanical strength, conductivity, and surface wettability, were analyzed. Using Response Surface Methodology (RSM) and Artificial Neural Network (ANN) modeling, the optimal scaffold (THAC) composition was determined to be 30.12% TSP, 21.69% HPMC, 12.05% ALG, and 36.14% CS. The ANN model outperformed RSM in predictive accuracy (R2>0.9). Mechanical testing demonstrated a Young's modulus of 0.905±0.103MPa and a compression strength of 0.398±0.028MPa, indicative of its resilience for cartilage engineering. Conductivity analysis revealed enhanced ionic conductance in wet conditions, highlighting its electrolyte-responsive behavior. Surface wettability tests showed a hydrophilic nature, with a contact angle of 58.08±6.84°, enabling superior water absorption. SEM analysis confirmed a uniform porous structure, while cytocompatibility studies with HeLa, MG -63 and ES-E14TG2a cells showed significant cell proliferation and attachment. These results underscore THAC's potential for applications in regenerative medicine, with the combination of RSM and ANN enabling precise tuning of scaffold properties for optimal performance in tissue engineering.

Collagen silver-doped hydroxyapatite scaffolds reinforced with 3D printed frameworks for infection prevention and enhanced repair of load-bearing bone defects.

Osteomyelitis, a severe bone infection, is an extremely challenging complication in the repair of traumatic bone defects. Furthermore, the use of long-term high-dose antibiotics in standard treatment increases the risks of antibiotic resistance. Herein, an antibiotic-free, collagen silver-doped hydroxyapatite (coll-AgHA) scaffold reinforced with a 3D printed polycaprolactone (PCL) framework was developed with enhanced mechanical properties to be used in the repair of load-bearing defects with antimicrobial properties as a preventative measure against osteomyelitis. The AgHA particles were fabricated in varying Ag doses and loaded within freeze-dried collagen scaffolds at two concentrations. The optimised Ag dose (1.5 mol% Ag) and AgHA concentration (200 wt%) within the collagen scaffold demonstrated in vitro osteogenic and antibacterial properties against Staphylococcus aureus (S. aureus), the main causative pathogen of osteomyelitis. The addition of the PCL framework to the coll-AgHA scaffolds significantly enhanced the compressive modulus from 4 kPa to 12 MPa while maintaining high porosity as well as both pro-osteogenic and antibacterial properties. The reinforced coll-AgHA scaffolds were implanted in vivo and demonstrated enhanced bone repair, significantly greater vessel formation, and calcified tissue in a load-bearing critical sized defect in rats. Taken together, these results confirm the capacity of this novel biomaterial scaffold as a preventative measure against infection in bone repair for use in load-bearing defects, without the use of antibiotics.&#xD.

Cellular Behaviors of Human Dermal Fibroblasts on Pyrolytically Stripped Carbon Nanofiber's Surface.

There has been limited exploration of carbon nanofiber as a scaffold for cellular attachment and proliferation. In this work, commercially available, pyrolytically stripped carbon nanofiber (cCNF) is deposited over electrospun nanofiber mats, polycaprolactone (PCL) and poly(D-lactide) (PDLA), to immobilize them and investigate whether the 3D cCNF layer's surface augments cell proliferation of human dermal fibroblasts (nHDF). Spectral characterizations, such as XRD and Raman, show that cCNF exhibited crystalline structure with a high graphitization degree. cCNF layers are modified to have an irregular or planar surface by simple agitation (s-cCNF) or probe sonication (p-cCNF) of the solution. The in vitro cell line studies revealed that p-cCNF is better than s-cCNF in providing a platform that supports a homogenous spread of the fibroblasts all over the nanofiber's surface. The p-cCNF-deposited PCL mat (p-cCNF@PCL) demonstrated cellular growth, similar to that of the neat PCL mat. However, the p-cCNF@PCL mat exhibited remarkable antibacterial properties by reducing the E. coli numbers, ≈16 times greater than the PCL mat. It is concluded that the immobilized, pyrolytically stripped carbon nanofiber's surface has the potential to accommodate cellular growth and inhibit bacterial colonies, suggesting the biomaterial scaffold is promising for in vivo and clinical applications of skin tissue regeneration.

Advancements in Bone Replacement Techniques-Potential Uses After Maxillary and Mandibular Resections Due to Medication-Related Osteonecrosis of the Jaw (MRONJ).

Maxillofacial bone defects can have a profound impact on both facial function and aesthetics. While various biomaterial scaffolds have shown promise in addressing these challenges, regenerating bone in this region remains complex due to its irregular shape, intricate structure, and differing cellular origins compared to other bones in the human body. Moreover, the significant and variable mechanical loads placed on the maxillofacial bones add further complexity, especially in cases of difficult-to-treat medical conditions. This review provides a brief overview of medication-related osteonecrosis of the jaw (MRONJ), highlighting the medication-induced adverse reactions and the associated clinical challenges in treating this condition. The purpose of this manuscript is to emphasize the role of biotechnology and tissue engineering technologies in therapy. By using scaffold materials and biofactors in combination with autologous cells, innovative solutions are explored for the repair of damaged facial bones. The ongoing search for effective scaffolds that can address these challenges and improve in vitro bone preparation for subsequent regeneration in the maxillofacial region remains critical. The primary purpose of this review is to spotlight current research trends and novel approaches in this area.

The role of biomaterials-based scaffolds in advancing skin tissue construct.

Despite extensive clinical studies and therapeutic interventions, addressing significant skin wounds remains challenging, necessitating novel approaches for effective regeneration therapy. In the current review, we analyzed and evaluated the application, advancements, and future directions of biomaterials-based scaffolds for skin tissue construct. In addition, we investigated the role of other biological substitutes in promoting wound healing and skin tissue regeneration. The review highlights the impact of biomaterial-based scaffolds on skin tissue regeneration and wound healing. After presenting the physiological process of skin tissue regeneration, the review emphasizes the different biochemical components significant for skin healing and regeneration. Subsequently, it delves into the role of scaffolds in skin tissue engineering. Recent advancements in nanotechnology are also highlighted with a specific focus on the utilization of nanomaterials for enhancing healing, facilitating tissue regeneration, and promoting skin reconstruction. Biomaterial scaffolds have emerged as a potential intervention for wound healing forming the foundation of skin tissue regeneration. These scaffolds, intricate three-dimensional frameworks, serve as carriers for cells, medications, and genes, facilitating their delivery into the body. The integration of degradable porous scaffolds with biological cells offers a promising avenue for tissue repair. Biomaterials play a crucial role in tissue engineering, providing temporary mechanical support and facilitating cellular processes to augment skin tissue regeneration.

Versatile platforms of mussel-inspired agarose scaffold for cell cultured meat.

Biomaterial scaffolds are critical for cell cultured meat production. polysaccharide scaffolds lack essential animal cell adhesion receptors, leading to significant challenges in cell proliferation and myogenic differentiation. Thus, enhancing cell adhesion and growth on polysaccharide scaffolds is strongly required to supply the gaps in cell-cultured meat production. This study aims to develop a multifunctional cell-responsive hydrogel scaffold for the in vitro production of myofibers and structured cell cultured meat through a "cell adhesion-proliferation-differentiation" strategy. A polydopamine coating was applied to agarose hydrogel scaffolds using a dipping technique. The capability of scaffolds for myofiber preparation was assessed by evaluating cell adhesion, proliferation, and myogenic differentiation. Utilizing isolated porcine skeletal muscle satellite cells (PSMSCs), the feasibility of structured cell cultured pork tissue supported by agarose hydrogel film scaffolds was further investigated through three-dimensional imaging and scanning electron microscopy analysis. The physicochemical properties of the structured cell cultured pork tissue were evaluated through staining and texture analysis. The incorporation of a polydopamine coating facilitated a remarkable 100% cell adhesion rate on agarose hydrogel scaffolds, which also demonstrated reusability. The agarose hydrogel scaffolds retained adequate mechanical properties, enabling the adhered cells to proliferate effectively and differentiate into myofiber. Moreover, isolated PSMSCs maintained growth potential on the agarose hydrogel scaffolds, thereby imparting the scaffolds with the ability to generate substantial quantities of multinucleated myofibers. Furthermore, we established a structured cell culture pork meat model, characterized by high-density myofibers and agarose hydrogel film scaffolds, which exhibited the texture and color typical of real pork. The innovative agarose/polydopamine scaffold functions as a multifunctional platform for cell culture, offering novel avenues for the diversification and scalable production of cultured meat, and promising significant reductions in production costs for cell cultured meat.

Potential applications of PLGA/PVA coaxial nanofibers with controlled release for guiding tissue regeneration

Abstract Biomedical scaffolds are increasingly used in bone repair due to their exceptional ability to support cell growth and proliferation. This study developed a multifunctional poly(lactic-co-glycolic acid) (PLGA)/polyvinyl alcohol (PVA)/metronidazole coaxial electrospun nanofiber membrane to overcome the limitations of current bone tissue self-repair mechanisms. Optimization of the coaxial electrospinning parameters significantly improved the membrane’s overall performance. Mechanical property testing revealed that the tensile strength increased from 4.304 ± 0.079 MPa to 6.915 ± 0.032 MPa as the shell layer feeding rate was increased. Drug release studies demonstrated a marked reduction in the initial burst release of metronidazole as the shell layer thickness increased. The release amount decreased from 86% to 34% by the third hour, and the release continued over the course of one week. Furthermore, the in vitro release model transitioned from first-order kinetics to Peppas-Sahlin kinetics. In vitro studies confirmed that the metronidazole-loaded coaxial fiber membrane exhibited excellent biocompatibility, antibacterial properties, and osteogenic potential. In conclusion, PLGA/PVA controlled-release nanofiber membranes loaded with antibacterial drugs offer great promise for bone tissue regeneration therapies.

Injectable oxidized high-amylose starch hydrogel scaffold for macrophage-mediated glioblastoma therapy.

Glioblastoma, characterized by rapid proliferation and invasiveness, is largely resistant to current treatment modalities. A major obstacle is the blood-brain barrier (BBB), which restricts the delivery of therapeutic agents as well as the infiltration of effective immune cells into glioblastoma. In this study, we developed an injectable oxidized high-amylose starch hydrogel (OHASM) to serve as a biomaterial scaffold for the delivery of macrophages and macrophage-polarizing drugs, aiming to bypass the BBB and enhance glioblastoma treatment. The in vitro and in vivo experiments confirmed the efficacy of the hydrogel in loading and delivering macrophages and polarizing drugs against glioblastoma. Additionally, the hydrogel's interconnected porous structure was conducive to cellular growth and activity, and its slow release of therapeutics contributed to the extended survival of treated mice in a mouse GL261 glioblastoma tumor model. The immunological mechanisms underlying the therapeutic efficacy were further elucidated, revealing the potential of the hydrogel system to modulate macrophage polarization and induce apoptosis in tumor cells via the poly ADP-ribose polymerase (PARP) pathway. The study underscores the potential of the hydrogel-based macrophage delivery strategy as an effective and safe treatment for glioblastoma, offering a promising avenue for clinical management of this aggressive brain cancer.

Multi-layered electrode constructs for neural tissue engineering

Neural tissue engineering offers promising therapies for multiple clinical applications. One important challenge in this field is to establish biomaterial scaffolds that present the cues required for neural tissue development....

Injectable, cryopreservable mesenchymal stromal cell-loaded microbeads for pro-angiogenic therapy: in vitro proof-of-concept

Despite their recognized potential for ischemic tissue repair, the clinical use of human mesenchymal stromal cells (hMSC) is limited by the poor viability of cells after injection and the variability of their paracrine function. In this study, we show how the choice of biomaterial scaffolds and the addition of cell preconditioning treatment can address these limitations and establish a proof-of-concept for cryopreservable hMSC-loaded microbeads. Injectable microbeads in chitosan, chitosan-gelatin, and alginate were produced using stirred emulsification to obtain a similar volume moment mean diameter (D[4,3]500 µm). Cell viability was determined through live/dead assays, and vascular endothelial growth factor (VEGF) release was measured by ELISA. Proangiogenic function was studied by measuring the wound closure velocity of endothelial cells (HUVEC) co-cultured with MSC-loaded microbeads. The effect of freeze-thawing on microbeads morphology, porosity, injectability and encapsulated MSC was also studied. hMSC-loaded chitosan-based microbeads were found to release 11-fold more VEGF than alginate microbeads (p˂0.0001) and chitosan-gelatin was chosen for further studies because it presented the best cell viability. Preconditioning with celastrol significantly enhanced the viability (1.12-fold) and VEGF release (1.40-fold) of MSC-loaded in chitosan-gelatin microbeads, as well as their proangiogenic paracrine function (1.2-fold; p˂0.05). In addition, preconditioning significantly enhanced the viability of hMSC after 1 and 3 days in low-serum medium after cryopreservation (p˂0.05). Cryopreserved hMSC-loaded microbeads maintained their mechanical properties, were easily injectable through a 23G needle, and maintained their paracrine function, enhancing the proliferation and migration of scratched HUVEC. This study shows the advantage of chitosan as a scaffold material and concludes that chitosan-gelatin microbeads with celastrol-preconditioned cells form a promising off-the-shelf, cryopreservable allogenic MSC product. In vivo testing is required to confirm their potential in treating ischemic diseases or other clinical applications.

Biomedical Application of Bovine Type I Collagen and Its Fabricated Scaffolds: A Review

The transformation of waste into wealth remains a challenging yet essential endeavor, offering opportunities for efficient solid waste management. Type I collagen, abundant in bovine tendons, serves as a valuable feedstock for the extraction of this biomaterial. Derived from slaughterhouse solid waste, bovine type I collagen acts as a foundational biomaterial for tissue engineering and regenerative medicine. This fibrous protein-based eco-material features customizable properties, including biodegradability, mechanical resilience, and surface modifiability, making it a promising alternative to synthetic and biodegradable polymers. The design and development of bioactive scaffolds remain a significant challenge in regenerative medicine, tissue engineering, and drug delivery. Collagen-based biomaterial scaffolds, which mimic the extracellular matrix, are extensively utilized as templates for tissue regeneration in biomedical applications. These scaffolds enhance wound healing and facilitate the maturation of collagen fibers, promoting the rapid formation of mature, aligned tissue at wound sites. This review provides a comprehensive analysis of the biomedical applications of collagen-based biomaterials, including their isolation and purification from bovine tendons, characterization, scaffold fabrication, ciprofloxacin/Triphala conjugation into scaffolds, biochemical and histological wound healing investigations, drug delivery, and cell culture applications. Recent advancements in chemically modified collagen and collagen-biodegradable polymer composites with controlled drug delivery for wound treatment, as well as collagen-based diffusion membranes for prolonged drug release, are also discussed.

Micro-CT Assessment During Embedding of Prototype Ti Alloy Multi-Spiked Connecting Scaffold in Subchondral Trabecular Bone of Osteoarthritic Femoral Heads, Depending on Host BMI.

The prototype of a biomimetic multi-spiked connecting scaffold (MSC-Scaffold) represents an essential innovation in the fixation in subchondral trabecular bone of components for a new generation of entirely cementless hip resurfacing arthroplasty (RA) endoprostheses. In designing such a functional biomaterial scaffold, identifying the microstructural and mechanical properties of the host bone compromised by degenerative disease is crucial for proper post-operative functioning and long-term maintenance of the endoprosthesis components. This study aimed to explore, depending on the occurrence of obesity, changes in the microstructure and mechanical properties of the subchondral trabecular bone in femoral heads of osteoarthritis (OA) patients caused by the MSC-Scaffold embedding. Computed microtomography (micro-CT) scanning of femoral heads from OA patients was conducted before and after the mechanical embedding of the MSC-Scaffold. Bone morphometric parameters such as bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) for regions surrounding the MSC-Scaffold were computed, and the mechanical properties such as bone density (ρB), bone compressive strength (S), and the Young's modulus (E) within these regions were calculated. A statistically significant increase in BV/TV (by 15.0% and 24.9%) and Tb.Th (by 13.1% and 42.5%) and a decrease in Tb.N (by 15.2% and 23.6%) were observed, which translates to an increase in ρB (by 15.0% and 24.9%), S (by 28.8% and 49.5%), and E (by 18.0% and 29.8%) in non-obese patients and obese patients, respectively. These changes in properties are favorable for the mechanical loads' transfer from the artificial joint surface via the MSC-Scaffold to the periarticular trabecular bone of the OA femoral head in the postoperative period.

Biological and Synthetic Materials in Mandibular Reconstruction

Mandibular reconstruction is a critical surgical procedure necessary for restoring both function and aesthetics following trauma, tumor resection, or congenital defects. Over time, a variety of biological and synthetic materials have been developed to address the challenges of reconstructing the complex anatomy of the mandible. Biological materials, such as autografts, offer superior biocompatibility and osteogenic potential, but are limited by donor site morbidity and graft availability. Allografts and xenografts provide more accessible alternatives but are associated with higher risks of immune rejection and slower integration. In contrast, synthetic materials like titanium, PEEK (polyether ether ketone), and hydroxyapatite provide excellent mechanical strength and durability but often lack osteoinductive properties, requiring surface modifications to improve tissue integration.This review aims to provide a comprehensive analysis of the current materials used in mandibular reconstruction, comparing their biocompatibility, mechanical properties, osteoinductive potential, and clinical outcomes. Additionally, the review explores the growing role of composite materials that combine the strength of synthetics with the biological activity of natural tissues, as well as the advent of tissue engineering approaches that incorporate stem cell therapies and biomaterial scaffolds to promote bone regeneration. Emerging technologies such as 3D printing of custom-made implants and the application of nanotechnology for enhanced integration and infection control are also discussed as promising directions for future clinical applications. The findings highlight the need for continued research into optimizing biomaterial design and improving regenerative therapies to enhance patient-specific outcomes, reduce complications, and foster successful long-term integration of reconstructed mandibular structures. This review provides a roadmap for advancing both material science and clinical practice in the field of mandibular reconstruction.

Decellularized Cell‐Secreted Extracellular Matrices as Biomaterials for Tissue Engineering

The extracellular matrix (ECM) is the naturally secreted biomaterial scaffold that provides support and regulates key aspects of cell behavior. This dynamic and complex network of structural proteins, proteoglycans, and soluble cues defines the cell microenvironment and is essential for tissue homeostasis. Because tissue engineering approaches aim to recapitulate aspects of the microenvironment to instruct tissue regeneration, ECM‐inspired or ‐derived scaffolds are some of the earliest tissue‐engineered constructs reported. However, conventional single‐protein constructs fail to provide the biochemical and structural complexity of the native ECM. Decellularized ECM is under investigation to improve cell adhesion, cell remodeling, migration, proliferation, and differentiation within tissue‐engineered constructs. However, challenges associated with poor mechanical properties and inherent chemical instability compared to synthetic or other natural polymers require additional considerations. This review describes the bioactive properties of ECM, current strategies to efficiently decellularize cell‐secreted and tissue‐derived ECM, standard fabrication techniques for ECM constructs, and current developments in the field of ECM‐based musculoskeletal platforms.

Silk Fibroin–Based Biomaterial Scaffold in Tissue Engineering: Present Persuasive Perspective

Silk Fibroin–Based Biomaterial Scaffold in Tissue Engineering: Present Persuasive Perspective

Quantifying Biomass and Visualizing Cell Coverage on Fibrous Scaffolds for Cultivated Meat Production.

Cultivated meat represents a transformative solution to environmental and ethical concerns of traditional meat industries, replicating livestock meat's texture and sensory attributes in vitro with a focus on cost, safety, and nutritional quality. Central to this process are biomaterial scaffolds that support tissue development from isolated animal cells grown in or on these matrices. Understanding scaffold interactions with cells, including scaffold degradation and biomass production, is crucial for process design and for scaling-up goals. In this article, we outline comprehensive methods to quantify scaffold-cell interactions for such scenarios, focusing on biomaterial scaffold degradation and changes in cell biomass [measured by cell weight, extracellular matrix (ECM) deposition, and cell coverage] during cell culture. We introduce two methodologies for assessing cell coverage: fixation and staining for detailed imaging analysis, and non-invasive, real-time evaluation across scaffolds. Here we focus on fiber-based scaffolds, while the assessments can be extrapolated to 2-dimensional (2D; films), and in part to 3-dimensional (3D; sponge) systems. Utilizing the C2C12 mouse myoblast cell line as a gold standard, the protocols deliver precise, step-by-step instructions for preparing fiber scaffolds (using silk proteins here), seeding cells, and monitoring key parameters for cultivated meat production, providing a framework for advancing cellular agriculture techniques. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Fabrication and preparation of silk fiber scaffolds for cell seeding Support Protocol 1: Cultivation of C2C12 cells and seeding onto fibrous scaffolds Basic Protocol 2: Quantification of decellularized yarn scaffold degradation during cell culture Basic Protocol 3: Quantification of biomass variation and ECM deposition on yarn scaffolds during C2C12 cell culture Basic Protocol 4: Visualization of cell-laden yarn scaffolds and determination of cell coverage ratio using confocal microscopy Support Protocol 2: Real-time imaging of cell-laden yarn scaffolds using Celigo system Support Protocol 3: Applying green CellTracker fluorescent probes to C2C12 cells seeded on yarn scaffolds.

Evaluation of Biomaterials in Periodontal Regeneration: A Literature Review.

The field of periodontal regeneration focuses on restoring the form and function of periodontal tissues compromised due to diseases affecting the supporting structures of teeth. Biomaterials have emerged as a vital component in periodontal regenerative therapy, offering a variety of properties that enhance cellular interactions, promote healing, and support tissue reconstruction. This review explores current advances in biomaterials for periodontal regeneration, including ceramics, polymers, and composite scaffolds, and their integration with biological agents like growth factors and stem cells. Specifically, biomaterials such as hydroxyapatite and bioactive glass provide scaffolding for cellular adhesion and proliferation, while synthetic and natural polymers offer flexibility and biocompatibility. Growth factors and bone morphogenic proteins (BMP) further support cell differentiation and tissue formation, enhancing clinical outcomes in periodontal defect repair. Moreover, stem cell integration with biomaterials, particularly the periodontal ligament stem cells (PDLSCs) and mesenchymal stem cells (MSCs), shows promise for complex tissue regeneration by stimulating targeted healing responses in periodontal tissue. Although clinical results are encouraging, challenges related to the selection of optimal biocompatible and bioactive materials and standardization of clinical protocols remain. This review examines the potential, limitations, and future directions for biomaterial-based strategies, highlighting the evolving role of these materials in achieving predictable and effective periodontal regeneration.

Incorporation of metal-doped silicate microparticles into collagen scaffolds combines chemical and architectural cues for endochondral bone healing.

Regeneration of large bone defects remains a clinical challenge until today. While existing biomaterials are predominantly addressing bone healing via direct, intramembranous ossification (IO), bone tissue formation via a cartilage phase, so-called endochondral ossification (EO) has been shown to be a promising alternative strategy. However, pure biomaterial approaches for EO induction are sparse and the knowledge how material components can have bioactive contribution to the required cartilage formation is limited. Here, we combined a previously developed purely architecture-driven biomaterial approach with the release of therapeutic metal ions from tailored silicate microparticles. The delivery platform was free of calcium phosphates (CaP) that are known to support IO but not EO and was employed for the release of lithium (Li), magnesium (Mg), strontium (Sr) or zinc (Zn) ions. We identified an ion-specific cellular response in which certain metal ions strongly enhanced cell recruitment into the material and showed superior chondrogenesis and deposition collagen II by human mesenchymal stromal cells (MSCs). At the same time, in some cases microparticle incorporation altered the mechanical properties of the biomaterial with consequences for cell-induced biomaterial contraction and scaffold wall deformation. Collectively, the results suggest that the incorporation of metal-doped silicate microparticles has the potential to further improve the bioactivity of architectured biomaterials for bone defect healing via EO. STATEMENT OF SIGNIFICANCE: Endochondral bone healing, a process that resembles embryonic skeletal development, has gained prominence in regenerative medicine. However, most therapeutic biomaterial strategies are not optimized for endochondral bone healing but instead target direct bone formation through IO. Here, we report on a novel approach to accelerate biomaterial-guided endochondral bone healing by combining cell-guiding collagen scaffolds with therapeutic metal-doped silicate microparticles. While other strategies, such as hypoxia-mimic drugs and iron-chelating biomaterials, have been documented in the literature before to enhance EO, our approach uniquely implements enhanced bioactivity into a previously developed biomaterial strategy for bone defect regeneration. Enhanced cell recruitment into the material and more pronounced chondrogenesis were observed for specific hybrid scaffold formulations, suggesting a high relevance of this new biomaterial for improved endochondral bone healing.

Advanced biomaterials for regenerative medicine and their possible therapeutic significance in treating COVID-19: a critical overview.

The potential of biomaterials in medical sciences has attracted much interest, especially in promoting tissue regeneration and controlling immune responses. As COVID-19 pandemic broke out, there was an increased interest in understanding more about how biomaterials could be employed to fight this dreaded disease, especially in the context of regenerative medicine. Out of the numerous regenerative medicine possibilities, stem cells and scaffolding (grafting) technology are two major areas in modern medicines and surgery. Mesenchymal stem cells are useful in tissue repair, tailored therapy and treating COVID-19. Using biomaterials in COVID-19 treatment is intricate that needs multi- and cross-disciplinary research. Cell-based therapy and organ transplant pose immunological rejection challenge. Immunomodulation enhanced, tumorigenicity decreased, inflammation addressed and tissue damage restricted bioengineered stem cells need clinical insights and validation. Advanced stem cell based therapies should ideally be effective, safe and scalable. Cost and scalability shall dictate the dawn of technoeconomically feasible regenerative medicine. A globally standard and uniform approval process could accelerate translational regenerative medicine. Researchers, patient advocacy organisations, the regulators and the biopharmaceutical stakeholders need to join hands for easy navigation of regulatory measures and expeditious market entry of regenerative medicine. This article summarises advances in biomaterials for regenerative medicine, and their possible therapeutic benefits in managing infectious diseases like COVID-19. It highlights the significant recent developments in biomaterial design, scaffold construction, and stem cell-based therapies to treat tissue damage and COVID-19 linked immunological disregulation. It also highlights the potential contribution of biomaterials towards creating novel treatment strategies to manage COVID-19.