Tissue Regeneration Therapy Research Articles

Biomechanical Insights into the Proteomic Profiling of Cells in Response to Red Light Absorption.

Photobiomodulation (PBM) is a promising non-invasive therapy for tissue repair, but its underlying cellular mechanisms are not fully understood. In this study, the biomechanical and proteomic responses of three cell types - keratinocytes (HACAT), fibroblasts (L929), and osteoblasts (OFCOLII) - exposed to red light (633 nm) are investigated using atomic force microscopy (AFM) and mass spectrometry-based proteomic analysis. Red light absorption resulted in cell-type-specific changes in viscoelastic properties, with fibroblasts exhibiting increased fluidity, reduced stiffness, and enhanced motility. Conversely, keratinocytes exhibited intensity-dependent responses, while osteoblasts appeared to be relatively insensitive to irradiation conditions. Proteomic profiling identified key signaling pathways involved in immune response, ATP production, and stress regulation. The immune and ATP pathways are strongly linked to the modulation of viscoelastic properties, particularly in fibroblasts, while weaker correlations wereobserved in keratinocytes. Cytoskeletal remodeling, primarily within the F-actin network, is identified as the main driver of mechanical alterations, with additional contributions from microtubules and intermediate filaments. These findings provide new insights into how red light absorption modulates cellular viscoelasticity through cytoskeletal remodeling, with potential applications in optimizing light-based therapies for tissue regeneration and diseasetreatment.

Advanced Platelet-Rich Fibrin (A-PRF) as Antibiotics Delivery System: In-Vitro Proof-of-Concept Study

Autologous blood centrifugation produces various forms of platelet concentrates widely used in tissue regenerative therapies due to their high concentrations of growth factors and abundance of autologous cells. Advanced Platelet-Rich Fibrin (A-PRF), introduced as a low-speed centrifugation product, contains an even higher concentration of growth factors, a greater number of cells, and a looser fibrin clot structure compared to previous Leukocyte and Platelet-Rich Fibrin (L-PRF). This study aims to assess the potential of A-PRF as a local delivery system for antibiotics. Different concentrations (0.5 mg/mL, 0.25 mg/mL, and 0.125 mg/mL) of injectable amoxicillin (AMX) and metronidazole (MTZ) were preliminarily tested for their impact on A-PRF clot formation, with 0.5 mg/mL selected for subsequent experiments. Blood samples from healthy volunteers were supplemented with antibiotics and centrifuged to form clots. Antibiotic-enriched A-PRF clots were immersed in phosphate-buffered saline (1x PBS) and analyzed at 24 h, 72 h, 7 days, and 14 days. AMX showed a consistent release (mean: 19.9 ± 4.8 ng/mL at 24 h) over 14 days, while MTZ demonstrated greater variability (mean: 12.8 ± 4.5 ng/mL at 24 h). AMX release remained constant over the 14-day period, with no significant variations among patients. In contrast, MTZ displayed a progressively lower release over time. Microbiological analysis revealed bacterial growth inhibition zones for Fusobacterium nucleatum (AMX: 23 mm, MTZ: 28 mm) and Prevotella intermedia (AMX: 34 mm, MTZ: 30 mm) at 24 h. These findings suggest that A-PRF can act as an effective local antibiotic delivery system, maintaining sustained antimicrobial activity and potentially reducing the need for systemic antibiotics.

T Cell-Derived Apoptotic Extracellular Vesicles Ameliorate Bone Loss via CD39 and CD73-Mediated ATP Hydrolysis.

Osteoporosis is a major public health concern characterized by decreased bone density. Among various therapeutic strategies, apoptotic extracellular vesicles (ApoEVs) have emerged as promising agents in tissue regeneration. Specifically, T cell-derived ApoEVs have shown substantial potential in facilitating bone regeneration. However, it remains unclear whether ApoEVs can promote bone mass recovery through enzymatic activity mediated by membrane surface molecules. Therefore, this study aimed to investigate whether T cell-derived ApoEVs could promote bone mass recovery in osteoporosis mice and reveal the underlying mechanisms. ApoEVs were isolated through sequential centrifugation, and their proteomic profiles were identified via mass spectrometry. Western blot and immunogold staining confirmed the enrichment of CD39 and CD73 on ApoEVs. The role of CD39 and CD73 in hydrolyzing adenosine triphosphate (ATP) to adenosine was evaluated by quantifying the levels of ATP and adenosine. Inhibitors of CD39 and CD73, and an A2BR antagonist were used to explore the molecular mechanism of ApoEVs in promoting bone regeneration. ApoEVs significantly reduced bone loss and promote the osteogenic differentiation of BMMSCs in ovariectomy (OVX) mice. We observed increased levels of extracellular ATP and a decrease in CD39 and CD73, key enzymes in ATP-to-adenosine conversion in bone marrow of OVX mice. We found that ApoEVs are enriched with CD39 and CD73 on their membranes, which enable the hydrolysis of extracellular ATP to adenosine both in vitro and in vivo. The adenosine generated by ApoEVs inhibits the inflammatory response and promotes osteogenesis through A2BR and downstream PKA signaling. T cell-derived ApoEVs are enriched with CD39 and CD73, enabling them to hydrolyze extracellular ATP to adenosine, thereby promoting bone regeneration via A2BR and PKA signaling pathway. Our data underscore the substantive role of T cell-derived ApoEVs to treat osteoporosis, thus providing new ideas for the development of ApoEVs-based therapies in tissue regeneration.

Harnessing whey protein nanobiomaterials for tissue regeneration and cancer therapy: A comprehensive guide to recent innovations

Harnessing whey protein nanobiomaterials for tissue regeneration and cancer therapy: A comprehensive guide to recent innovations

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.

Nanomaterial application for protein delivery in bone regeneration therapy.

Bone fractures must undergo a complex healing process involving intricate cellular and molecular mechanisms. They require a suitable biological environment to restore skeletal stability and resolve inflammation. Scaffolds play a vital role in bone regeneration, thus reducing disease burden. Autologous bone graft represents the gold standard of therapy. However, its application is limited due to various reasons. Nanotechnology, in the form of nanomaterials and nano-drug delivery systems, has been proven to increase the potency of active substances in mimicking extracellular matrix (ECM), thereby providing physical support benefits and enhancing therapeutic effectiveness. Various materials, including protein, metal oxide, hydroxyapatite, and silica are modified with nanoparticle technology for the purposes of tissue regeneration therapy. Moreover, the properties of nanomaterials such as size, seta potential, and surface properties will affect their effectiveness in bone regeneration therapy. This review provides insights that deepen the knowledge of the manufacturing and application of nanomaterials as a therapeutic agent for bone regeneration.

The Hippo Signaling Pathway Manipulates Cellular Senescence.

The Hippo pathway, a kinase cascade, coordinates with many intracellular signals and mediates the regulation of the activities of various downstream transcription factors and their coactivators to maintain homeostasis. Therefore, the aberrant activation of the Hippo pathway and its associated molecules imposes significant stress on tissues and cells, leading to cancer, immune disorders, and a number of diseases. Cellular senescence, the mechanism by which cells counteract stress, prevents cells from unnecessary damage and leads to sustained cell cycle arrest. It acts as a powerful defense mechanism against normal organ development and aging-related diseases. On the other hand, the accumulation of senescent cells without their proper removal contributes to the development or worsening of cancer and age-related diseases. A correlation was recently reported between the Hippo pathway and cellular senescence, which preserves tissue homeostasis. This review is the first to describe the close relationship between aging and the Hippo pathway, and provides insights into the mechanisms of aging and the development of age-related diseases. In addition, it describes advanced findings that may lead to the development of tissue regeneration therapies and drugs targeting rejuvenation.

Integrating Robotics in Bioprinting: Advancements in 3D-Printed Tissue and Organ Engineering

The integration of robotics in bioprinting is revolutionizing the field of tissue and organ engineering, enabling unprecedented precision, scalability, and complexity in 3D-printed biological structures. This research explores the advancements brought about by robotic systems in bioprinting processes, focusing on their role in enhancing the fabrication of tissues and organs with intricate architectures and functional properties. Key areas of investigation include robotic-assisted multi-material deposition, real-time process monitoring, and adaptive printing techniques that ensure high fidelity and cell viability. The study also examines the incorporation of robotics into scalable bioprinting workflows for large-scale tissue engineering and transplantable organ production. Ethical considerations, such as regulatory challenges and equitable access, are addressed to highlight the societal implications of these innovations. By bridging robotics, bioengineering, and regenerative medicine, this research underscores the transformative potential of robotic-assisted bioprinting in addressing critical healthcare challenges, including organ shortages and personalized medicine. With advancements in precision and adaptability, robotic systems are poised to reshape the future of bioprinting, paving the way for breakthroughs in tissue engineering and regenerative therapies.

Optimizing the Electrical Microenvironment Provided by 3D Micropillar Topography on a Piezoelectric BaTiO3 Substrate to Enhance Osseointegration.

The electrical properties of bone implant scaffolds are a pivotal factor in regulating cellular behavior and promoting osteogenesis. The previous study shows that built-in electric fields established between electropositive nanofilms and electronegative bone defect walls are beneficial for promoting bone defect healing. Considering that the physiological electrical microenvironment is spatially distributed in 3D, it is imperative to establish a 3D spatial charged microenvironment on bone scaffolds to optimize the efficacy of osseointegration. Nevertheless, this still poses a formidable challenge. Here, a bone repair strategy that utilizes micro-scale 3D topography is developed on a piezoelectric BaTiO3 (BTO) substrate to provide 3D spatial electrical stimulation. The BTO micropillar arrays, especially with a height of 50 µm and positive-charge distribution (50 µm positive), promote the spreading, cytoskeletal reorganization, focal adhesion maturation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). They enhanced the clustering of mechanosensing integrin α5 in BMSCs. The biomimetic 3D spatial electrical microenvironment accelerated bone repair and osseointegration in a rat femoral diaphysis defect repair model. The study thus reveals that implants with a 3D spatial electrical microenvironment can significantly enhance osseointegration, thereby providing a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies.

Assessing the Effectiveness of A-PRF+ for Treating Periodontal Defects: A Prospective Interventional Pilot Study Involving Smokers.

Background and Objectives: This study aimed to evaluate the effects of advanced platelet-rich fibrin (A-PRF+) tissue regeneration therapy on clinical periodontal parameters in non-smokers and smoker patients. The anticipated biological mechanisms of A-PRF+ include stimulating angiogenesis, thereby promoting the formation of new blood vessels, which is essential for tissue healing. Additionally, A-PRF+ harnesses the regenerative properties of platelet-rich fibrin, contributing to the repair and regeneration of periodontal tissues. Materials and Methods: The study was conducted on 55 patients, divided into two groups: non-smoker patients (n = 29) and smoker patients (n = 26). A single operator conducted the surgical procedure. Following the administration of local anesthesia with articaine 4% with adrenaline 1:100,000 precise intracrevicular incisions were made, extending towards the adjacent teeth, until the interproximal spaces, with meticulous attention to conserving the interdental gingival tissue to the greatest extent possible. Extended, full-thickness vestibular and oral flaps were carefully lifted, and all granulation tissue was meticulously removed from the defect without altering the bone contour. After debridement of the defects, A-PRF+ was applied. BOP (bleeding on probing), PI (plaque index), CAL (clinical attachment loss), and probing depth (PD) were determined at baseline and six months post-surgery. Results: Significant reductions were observed in PD and CAL after six months. In the non-smokers group, PD decreased from 7.0 ± 1.0 mm to 3.1 ± 0.1 mm (p < 0.001), while in the smokers group, PD decreased from 6.9 ± 1.1 mm to 3.9 ± 0.3 mm (p < 0.001). CAL decreased in the non-smokers group from 5.8 ± 0.7 mm to 2.6 ± 0.2 mm and from 5.7 ± 0.9 mm to 3.2 ± 0.2 mm (p < 0.001) in smokers. Notably, the reductions in CAL and PD were statistically more significant in the non-smokers group. Conclusions: Even though the clinical periodontal improvements were considerable in smoker patients, they did not reach the level observed in non-smoker patients.

Establishment of Periodontal Ligament Stem Cell-like Cells Derived from Feeder-Free Cultured Induced Pluripotent Stem Cells.

The periodontal ligament (PDL) is a fibrous connective tissue that connects the cementum of the root to the alveolar bone. PDL stem cells (PDLSCs) contained in the PDL can differentiate into cementoblasts, osteoblasts, and PDL fibroblasts, with essential roles in periodontal tissue regeneration. Therefore, PDLSCs are expected to be useful in periodontal tissue regeneration therapy. In a previous study, we differentiated induced pluripotent stem cells (iPSCs) into PDLSC-like cells (iPDLSCs), which expressed PDL-related markers and mesenchymal stem cell (MSC) markers; they also exhibited high proliferation and multipotency. However, the iPSCs used in this differentiation method were cultured on mouse embryonic fibroblasts; thus, they constituted on-feeder iPSCs (OF-iPSCs). Considering the risk of contamination with feeder cell-derived components, iPDLSCs differentiated from OF-iPSCs (ie, OF-iPDLSCs) are unsuitable for clinical applications. In this study, we aimed to obtain PDLSC-like cells from feeder-free iPSCs (FF-iPSCs) using OF-iPDLSC differentiation method. First, we differentiated FF-iPSCs into neural crest cell-like cells (FF-iNCCs) and confirmed that FF-iNCCs expressed NCC markers (eg, Nestin and p75NTR). Then, we cultured FF-iNCCs on human primary PDL cell-derived extracellular matrix for 2 weeks; the resulting cells were named FF-iPDLSCs. FF-iPDLSCs exhibited higher expression of PDL-related and MSC markers compared with OF-iPDLSCs. FF-iPDLSCs also demonstrated proliferation and multipotency in vitro. Finally, we analyzed the ability of FF-iPDLSCs to form periodontal tissue invivo upon subcutaneous transplantation with β-tricalcium phosphate scaffolds into dorsal tissues of immunodeficient mice. Eight weeks after transplantation, FF-iPDLSCs had formed osteocalcin-positive bone/cementum-like tissues and collagen 1-positive PDL-like fibers. These results suggested that we successfully obtained PDLSC-like cells from FF-iPSCs. Our findings will contribute to the development of novel periodontal regeneration therapies.

Pepgen-P15 delivery to bone: A novel 3D printed scaffold for enhanced bone regeneration

Pepgen-P15 is a combination of an organic hydroxyapatite matrix derived from bovine sources, combined with a synthetic peptide known as P-15. The interaction between α2β1 integrin and the P15 chain triggers both intracellular and extracellular signaling pathways, resulting in the production of growth factors. Three-dimensional (3D) printing has recently emerged as an innovative strategy for developing personalized therapies in bone tissue regeneration. In this research, various ratios of calcium magnesium silicate (bredigite) nanoparticles were used to modify 3D printed scaffolds made of xanthan gum and polycaprolactone (PCL) via fused deposition modeling (FDM). Scaffolds were subsequently treated with an alkaline solution, covered with graphene oxide, and finally, Pepgen-P15 was applied. the effects of xanthan gum were assessed using swellability and contact angle tests. The results indicated that, the prepared scaffolds exhibited suitable degradation rates, mechanical characteristics, and apatite formation. Alizarin red and alkaline phosphatase assays were also conducted to evaluate the scaffolds’ effectiveness in promoting bone cell differentiation during cell culture. Furthermore, the surface of the scaffold was examined to determine the amount of Pepgen-P15 loaded and released. According to the findings, the scaffold composed of 20 % bredigite and 0.3 % graphene oxide, coated with Pepgen-P15, demonstrate optimal mechanical properties, cell adherence, development, and proliferation. Typically, it is a good candidate for use in bone tissue engineering.

Development of Scaffolds with Chitosan Magnetically Activated with Cobalt Nanoferrite: A Study on Physical-Chemical, Mechanical, Cytotoxic and Antimicrobial Behavior.

Background/Objectives: This study investigates the development of 3D chitosan-x-cobalt ferrite scaffolds (x = 5, 7.5, and 10 wt%) with interconnected porosity for potential biomedical applications. The objective was to evaluate the effects of magnetic particle incorporation on the scaffolds' structural, mechanical, magnetic, and biological properties, specifically focusing on their biocompatibility and antimicrobial performance. Methods: Scaffolds were synthesized using freeze-drying, while cobalt ferrite nanoparticles were produced via a pilot-scale combustion reaction. The scaffolds were characterized for their physical and chemical properties, including porosity, swelling, and mechanical strength. Hydrophilicity was assessed through contact angle measurements. Antimicrobial efficacy was evaluated using time kill kinetics and agar diffusion assays, and biocompatibility was confirmed through cytotoxicity tests. Results: The incorporation of cobalt ferrite increased magnetic responsiveness, altered porosity profiles, and influenced swelling, biodegradation, and compressive strength, with a maximum value of 87 kPa at 7.5 wt% ferrite content. The scaffolds maintained non-toxicity and demonstrated bactericidal activity. The optimal concentration for achieving a balance between structural integrity and biological performance was found at 7.5 wt% cobalt ferrite. Conclusions: These findings suggest that magnetic chitosan-cobalt ferrite scaffolds possess significant potential for use in biomedical applications, including tissue regeneration and advanced healing therapies. The incorporation of magnetic properties enhances both the structural and biological functionalities, presenting promising opportunities for innovative therapeutic approaches in reconstructive procedures.

Local and Systemic Peptide Therapies for Soft Tissue Regeneration: A Narrative Review.

Background: The musculoskeletal system, due to inherent structure and function, lends itself to contributing toward joint pain, whether from inflammatory disorders such as rheumatoid arthritis, degenerative diseases such as osteoarthritis, or trauma causing soft tissue injury. Administration of peptides for treatment of joint pain or inflammation is an emerging line of therapy that seeks to offer therapeutic benefits while remaining safe and relatively non-invasive. Purpose: The purpose of this study is to review the current literature on existing oral peptide agents, intra-articular peptide agents, and new developments in human trials to assess route of administration (RoA) for drug delivery in terms of soft tissue regeneration. Study Design: Narrative Review. Methods: A comprehensive literature search was conducted using the PubMed database. The search included medical subject headings (MeSH) terms related to peptide therapy, soft tissue regeneration, and RoA. Inclusion criteria comprised articles focusing on the mechanisms of action of peptides, clinical or biochemical outcomes, and review articles. Exclusion criteria included insufficient literature or studies not meeting the set evidence level. Conclusion: The review identified various peptides demonstrating efficacy in soft tissue repair. Oral and intra-articular peptides showed distinct advantages in soft tissue regeneration, with intra-articular routes providing localized effects and oral routes offering systemic benefits. However, both routes have limitations in bioavailability and absorption. Still in their infancy, further inquiries/research into the properties and efficacy of emerging peptides will be necessary before widespread use. As a viable alternative prior to surgical intervention, peptide treatments present as promising candidates for positive outcomes in soft tissue regeneration.

Developments in Alloplastic Bone Grafts and Barrier Membrane Biomaterials for Periodontal Guided Tissue and Bone Regeneration Therapy.

Periodontitis is a serious form of oral gum inflammation with recession of gingival soft tissue, destruction of the periodontal ligament, and absorption of alveolar bone. Management of periodontal tissue and bone destruction, along with the restoration of functionality and structural integrity, is not possible with conventional clinical therapy alone. Guided bone and tissue regeneration therapy employs an occlusive biodegradable barrier membrane and graft biomaterials to guide the formation of alveolar bone and tissues for periodontal restoration and regeneration. Amongst several grafting approaches, alloplastic grafts/biomaterials, either derived from natural sources, synthesization, or a combination of both, offer a wide variety of resources tailored to multiple needs. Examining several pertinent scientific databases (Web of Science, Scopus, PubMed, MEDLINE, and Cochrane Library) provided the foundation to cover the literature on synthetic graft materials and membranes, devoted to achieving periodontal tissue and bone regeneration. This discussion proceeds by highlighting potential grafting and barrier biomaterials, their characteristics, efficiency, regenerative ability, therapy outcomes, and advancements in periodontal guided regeneration therapy. Marketed and standardized quality products made of grafts and membrane biomaterials have been documented in this work. Conclusively, this paper illustrates the challenges, risk factors, and combination of biomaterials and drug delivery systems with which to reconstruct the hierarchical periodontium.

Mitochondria-targeted drug delivery system based on tetrahedral framework nucleic acids for bone regeneration under oxidative stress

Oxidative stress is present in many diseases and severely affects tissue reconstruction and regeneration. Many traditional Chinese medicinal monomers have excellent antioxidant effects; however, most cannot target the mitochondria, where oxidative stress is produced. In this study, a mitochondria-targeted antioxidant delivery system based on tetrahedral framework nucleic acids (tFNAs) is developed to combat oxidative stress. Antioxidant quercetin cargoes can be effectively loaded into the tFNA “trucks”, and the trucks are modified with mitochondria-targeting molecules to act as “headlights” to efficiently transport the cargo to the mitochondria. These results confirm that the delivery system can be efficiently loaded with quercetin and target the mitochondria. Both in vitro and in vivo studies confirm that the delivery system resists oxidative stress and inflammatory responses in a diabetic periodontitis model, which suffers from severe oxidative stress. The constructed delivery system delays the destruction of periodontal tissues, and promotes periodontal tissue regeneration. This study provides a new strategy for the efficient and targeted delivery of antioxidants, which is of great significance for the therapy of oxidative stress-related diseases and tissue regeneration.

Stimuli-Responsive Codelivery System-Embedded Polymeric Nanofibers with Synergistic Effects of Growth Factors and Low-Intensity Pulsed Ultrasound to Enhance Osteogenesis Properties.

The present work aims to develop optimized scaffolds for bone repair by incorporating mesoporous nanoparticles into them, thereby combining bioactive factors for cell growth and preventing rapid release or loss of effectiveness. We synthesized biocompatible and biodegradable scaffolds designed for the controlled codelivery of curcumin (CUR) and recombinant human bone morphogenic protein-2 (rhBMP-2). Active agents in dendritic silica/titania mesoporous nanoparticles (DSTNs) were incorporated at different weight percentages (0, 2, 5, 7, 9, and 10 wt %) into a matrix of polycaprolactone (PCL) and polyethylene glycol (PEG) nanofibers, forming the CUR-BMP-2@DSTNs/PCL-PEG delivery system (S0, S2, S5, S7, S9, and S10, respectively, with the number showing the weight percentage). To enhance the formation process, the system was treated using low-intensity pulsed ultrasound (LIPUS). Different advanced methods were employed to assess the physical, chemical, and mechanical characteristics of the fabricated scaffolds, all confirming that incorporating the nanoparticles improves their mechanical and structural properties. Their hydrophilicity increased by approximately 25%, leading to ca. 53% enhancement in their water absorption capacity. Furthermore, we observed a sustained release of approximately 97% for CUR and 70% for BMP-2 for the S7 (scaffold with 7 wt % DSTNs) over 28 days, which was further enhanced using ultrasound. In vitro studies demonstrated accelerated scaffold biodegradation, with the highest level observed in S7 scaffolds, approximately three times higher than the control group. Moreover, the cell viability and proliferation on DSTNs-containing scaffolds increased when compared to the control group. Overall, our study presents a promising nanocomposite scaffold design with notable improvements in structural, mechanical, and biological properties compared to the control group, along with controlled and sustained drug release capabilities. This makes the scaffold a compelling candidate for advanced bone tissue engineering and regenerative therapies.

Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopaedic surgery cases. This review explores the involvement of EVs in nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-free therapies. It underscores the importance of bioengineers comprehending and manipulating EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

Activating the healing process: three-dimensional culture of stem cells in Matrigel for tissue repair

BackgroundTo establish a strategy for stem cell-related tissue regeneration therapy, human gingival mesenchymal stem cells (hGMSCs) were loaded with three-dimensional (3D) bioengineered Matrigel matrix scaffolds in high-cell density microtissues to promote local tissue restoration.MethodsThe biological performance and stemness of hGMSCs under 3D culture conditions were investigated by viability and multidirectional differentiation analyses. A Sprague‒Dawley (SD) rat full-thickness buccal mucosa wound model was established, and hGMSCs/Matrigel were injected into the submucosa of the wound. Autologous stem cell proliferation and wound repair in local tissue were assessed by histomorphometry and immunohistochemical staining.ResultsThree-dimensional suspension culture can provide a more natural environment for extensions and contacts between hGMSCs, and the viability and adipogenic differentiation capacity of hGMSCs were significantly enhanced. An animal study showed that hGMSCs/Matrigel significantly accelerated soft tissue repair by promoting autologous stem cell proliferation and enhancing the generation of collagen fibers in local tissue.ConclusionThree-dimensional cell culture with hydrogel scaffolds, such as Matrigel, can effectively improve the biological function and maintain the stemness of stem cells. The therapeutic efficacy of hGMSCs/Matrigel was confirmed, as these cells could effectively stimulate soft tissue repair to promote the healing process by activating the host microenvironment and autologous stem cells.Graphical abstract

Advanced Immunomodulatory Biomaterials for Therapeutic Applications.

The multifaceted biological defense system modulating complex immune responses against pathogens and foreign materials plays a critical role in tissue homeostasis and disease progression. Recently developed biomaterials that can specifically regulate immune responses, nanoparticles, graphene, and functional hydrogels have contributed to the advancement of tissue engineering as well as disease treatment. The interaction between innate and adaptive immunity, collectively determining immune responses, can be regulated by mechanobiological recognition and adaptation of immune cells to the extracellular microenvironment. Therefore, applying immunomodulation to tissue regeneration and cancer therapy involves manipulating the properties of biomaterials by tailoring their composition in the context of the immune system. This review provides a comprehensive overview of how the physicochemical attributes of biomaterials determine immune responses, focusing on the physical properties that influence innate and adaptive immunity. This review also underscores the critical aspect of biomaterial-based immune engineering for the development of novel therapeutics and emphasizes the importance of understanding the biomaterials-mediated immunological mechanisms and their role in modulating the immune system.