Search Results (122)

Cartilage damage, particularly in the knee joint, presents a significant challenge in regenerative medicine due to its limited capacity for self-repair. Conventional treatments like microfracture surgery, autologous chondrocyte implantation (ACI), and osteochondral allografts often fall short, particularly in cases of larger defects or degenerative conditions. This has led to a growing interest in tissue engineering approaches that utilize biomaterial scaffolds to support cartilage regeneration. Among the many materials explored, chitosan—a naturally derived polysaccharide—has gained attention for its biocompatibility, biodegradability, and structural resemblance to the extracellular matrix (ECM) of cartilage. Recent advances in scaffold design have focused on modifying chitosan to improve its mechanical properties and enhance its biological performance. These modifications include chemical crosslinking, the incorporation of bioactive molecules, and the development of composite formulations. Such enhancements have allowed chitosan-based scaffolds to better support mesenchymal stem cell (MSC) differentiation into chondrocytes, paving the way for improved regenerative strategies. This review explores the latest progress in chitosan scaffold fabrication, preclinical findings, and the transition toward clinical applications. It also discusses the challenges that need to be addressed, such as mechanical stability, degradation rates, and the successful translation of research into viable therapeutic solutions. Full article

Organoids are three-dimensional tissue culture models derived from stem cells, and they have become one of the most valuable tools in biomedical research. These self-organizing miniature organs mimic the structure−function properties of their in vivo counterparts and offer an exceptional prospective for disease modeling, drug discovery, and regenerative medicine. By replicating the complexity of human tissue, organoids enable the study of disease pathophysiology, tissue development, and cellular interactions in a highly controlled and manipulable environment. Recent developments in organoid technology have enabled the production of functional organoids of various tissues. These systems have proven to be highly promising tools for personalized medicine. In addition, organoids have also raised hopes for the development of functional transplantable organs, transforming the study of regenerative medicine. This review provides an overview of the current state of organoid technology and its application and prospects and focuses on the transformative impact of organoid technology on biomedical research and its contribution to human health. Full article

Infectious wounds pose formidable clinical challenges due to hypoxia, exacerbated inflammation, and persistent microbial colonization. To address this, we developed a bioinspired multifunctional hydrogel (PTDPs) through the in situ freeze-thaw co-assembly of polyvinyl alcohol (PVA), tea polyphenols (TP), polydopamine (PDA), and marine-derived self-assembling peptides (AAPs). The resultant PTDP hydrogel formed an intricate hydrogen-bonded network that enhanced mechanical robustness and substrate adhesion. TP and PDA synergistically confer potent antioxidant properties: TP scavenges radicals via phenolic hydroxyl groups while PDA enhances responsiveness to diverse radicals in hypoxic environments. Integrated with AAPs’ pro-regenerative functions and PDA’s broad-spectrum antimicrobial efficacy, this system generates therapeutic synergy. Characterization revealed outstanding physicochemical properties including tunable plasticity, high swelling ratios, and sustained hydration retention. In vitro studies demonstrated potent antioxidant activity, efficient inhibition of Staphylococcus aureus and Escherichia coli proliferation, and cytocompatibility facilitating endothelial cell migration/proliferation. In murine full-thickness infected wound models, the PTDP hydrogel significantly accelerated wound closure, enhanced neovascularization, and improved collagen deposition, underscoring its potential as an innovative therapeutic platform for infected and chronic wounds with strong translational prospects. Full article

Cartilage tissue engineering (CTE) is an advancing field focused on developing biomimetic scaffolds to overcome cartilage’s inherently limited self-repair capacity. Smart hydrogels (SHs) have gained prominence among the various scaffold materials due to their ability to modulate cellular behavior through tunable mechanical and biochemical properties. These hydrogels respond dynamically to external stimuli, offering precise control over biological processes and facilitating targeted tissue regeneration. Recent advances in fabrication technologies have enabled the design of SHs with sophisticated architecture, improved mechanical strength, and enhanced biointegration. Key features such as injectability, controlled biodegradability, and stimulus-dependent release of biomolecules make them particularly suitable for regenerative applications. The incorporation of nanoparticles further improves mechanical performance and delivery capability. In addition, shape memory and self-healing properties contribute to the scaffolds’ resilience and adaptability in dynamic physiological environments. An emerging innovation in this area is integrating artificial intelligence (AI) and omics-based approaches that enable high-resolution profiling of cellular responses to engineered hydrogels. These data-driven tools support the rational design and optimization of hydrogel systems and allow the development of more effective and personalized scaffolds. The convergence of smart hydrogel technologies with omics insights represents a transformative step in regenerative medicine and offers promising strategies for restoring cartilage function. Full article

Spinal cord injury (SCI) is a debilitating neurological condition that leads to severe disabilities, significantly reducing patients’ quality of life and imposing substantial societal and economic burdens. SCI involves a complex pathogenesis, including primary irreversible damage and secondary injury driven by neuroinflammation, apoptosis, and ischemia. Current treatments often provide limited efficacy, underscoring the urgent need for innovative therapeutic strategies. This paper aims to explore the potential use of stem cell (SC) therapy and exosome-based treatments as transformative approaches for managing SCI and mitigating associated disabilities. SCs, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and embryonic stem cells (ESCs), demonstrate regenerative capabilities, including self-renewal, differentiation into neurons and glial cells, and modulation of the injury microenvironment. These properties enable SCs to reduce inflammation, inhibit apoptosis, and promote neuronal regeneration in preclinical models. Exosome-based therapies, derived from SCs, offer a novel alternative by addressing challenges like immune rejection and tumorigenicity. Exosomes deliver biomolecules, such as miRNAs, fostering anti-inflammatory, anti-apoptotic, and pro-regenerative effects. They have shown efficacy in improving motor function, reducing glial scarring, and enhancing axonal regrowth in SCI models. The objective of this paper is to provide a comprehensive review of SC therapy and exosome-based approaches, emphasizing their potential to revolutionize SCI management while addressing ethical concerns, immune rejection, and the need for large-scale clinical trials. These therapies hold promise for improving recovery outcomes and alleviating the profound disabilities associated with SCI. Full article

Background/Objectives: Efficient wound treatment embraces the management of four overlapping phases, starting with hemostasis, an immediate physiological response aimed at stopping bleeding from damaged blood vessels caused by skin injury. This paper proposes an innovative, nature-based hemostatic biomaterial designed to assist natural self-healing regenerative mechanisms. Methods: Light, transparent, and skin-adhesive films based on κ-carrageenan, meadow polyfloral honey, and Calendula officinalis flower extract were fabricated via solution casting. Comprehensive characterization revealed the physicochemical, structural, swelling, and barrier properties and the influence of each bioactive compound utilized for film preparation. Results: The samples subcutaneously implanted in Wistar rats induced vascularization, deposition of collagen, and orientation of collagen fibers while being fully phagocytosed and gradually biodegraded. The rat tail-cut model demonstrated that the films significantly reduced blood loss (0.1875 ± 0.0732 g) compared to the control (0.7837 ± 0.3319 g), and hemostasis was achieved notably faster (355.75 ± 71.42 s) than in the control group (704.25 ± 85.29 s). The rat liver punch biopsy model confirmed reduced blood loss (2.8025 ± 1.5174 g) and shorter time to hemostasis (303.25 ± 77.90 s) compared to the control (3.1475 ± 1.5413 g, 383.00 ± 36.53 s). Conclusions: The results indicate the great potential of the fabricated films as hemostatic wound dressings. Full article

The advancement of Vital Pulp Therapy (VPT) in dentistry has shown remarkable progress, with a focus on innovative materials and scaffolds to facilitate reparative dentin formation and tissue regeneration. A comprehensive search strategy was performed across PubMed, Scopus, and Web of Science using keywords such as “vital pulp therapy”, “biomaterials”, “dentin regeneration”, and “growth factors”, with filters for English language studies published in the last 10 years. The inclusion criteria focused on in vitro, in vivo, and clinical studies evaluating traditional and next-generation biomaterials for pulp capping and tissue regeneration. Due to the limitations of calcium-based cements in tissue regeneration, next-generation biomaterials like gelatin, chitosan, alginate, platelet-rich fibrins (PRF), demineralized dentin matrix (DDM), self-assembling peptides, and DNA-based nanomaterials were explored for their enhanced biocompatibility, antibacterial properties, and regenerative potential. These biomaterials hold great potential in enhancing VPT outcomes, but further research is required to understand their efficacy and impact on dentin reparative properties. This review explores the mechanisms and properties of biomaterials in dentin tissue regeneration, emphasizing key features that enhance tissue regeneration. These features include biomaterial sources, physicochemical properties, and biological characteristics that support cells and functions. The discussion also covers the biomaterials’ capability to encapsulate growth factors for dentin repair. The development of innovative biomaterials and next-generation scaffold materials presents exciting opportunities for advancing VPT in dentistry, with the potential to improve clinical outcomes and promote tissue regeneration in a safe and effective manner. Full article

Conventionally, root canal treatment is performed when the dental pulp is severely damaged or lost due to dental trauma or bacterial endodontic infections. This treatment involves removing the compromised or infected pulp tissue, disinfecting the root canal system, and sealing it with inert, non-degradable materials. However, contemporary endodontic treatment has shifted from merely obturating the root canal system with inert materials to guiding endodontic tissue regeneration through biological approaches. The ultimate goal of regenerative endodontics is to restore dental pulp tissue with structural organization and functional characteristics akin to the native pulp, leveraging advancements in tissue engineering and biomaterial sciences. Dental pulp tissue engineering commonly employs scaffold-based strategies, utilizing biomaterials as initial platforms for cell and growth factor delivery, which subsequently act as scaffolds for cell proliferation, differentiation and maturation. However, cells possess an intrinsic capacity for self-organization into spheroids and can generate their own extracellular matrix, eliminating the need for external scaffolds. This self-assembling property presents a promising alternative for scaffold-free dental pulp engineering, addressing limitations associated with biomaterial-based approaches. This review provides a comprehensive overview of cell-based, self-assembling and scaffold-free approaches in dental pulp tissue engineering, highlighting their potential advantages and challenges in advancing regenerative endodontics. Full article

The development of scaffold materials that effectively mimic the extracellular matrix while enabling controlled nutrient delivery remains a critical challenge in tissue engineering. Multi-channel collagen gels (MCCGs), which form through the competition between gelation and phase separation, have emerged as promising scaffolds due to their self-organized vessel-like structures. However, a systematic understanding of the relationship between the gelation conditions and functional properties is limited. In this study, MCCGs were developed as controllable perfusion culture scaffolds by investigating the effects of carbonate buffer concentration on channel formation, permeation behavior, and cell proliferation. MCCGs were prepared using different carbonate buffer concentrations (12.5, 25, and 50 mM), with 25 mM producing optimal channel formation, characterized by an approximately 60% channel area fraction and uniform distribution. Permeation studies revealed that fluid transport through MCCGs is governed by a complex interplay between capillary phenomena and hydraulic pressure, whose relative dominance shifts with flow rate: capillary action dominates at low flow rates (2.5 mL/h), whereas hydraulic pressure becomes the primary driver at higher rates (5.0–10.0 mL/h). Cell proliferation assessments demonstrated that MCCGs prepared with 25 mM carbonate buffer provided the most favorable microenvironment, achieving superior cell growth over 168 h through balanced media supply and cell adhesion area. This optimization approach through buffer concentration adjustment offers a cost-effective and scalable method for developing perfusion culture scaffolds, advancing both the fundamental understanding of functional gel systems and practical applications in tissue engineering and regenerative medicine. Full article

Articular cartilage faces challenges in self-repair due to the lack of blood vessels and limited chondrocyte concentration. Polydeoxyribonucleotide (PDRN) shows promise for promoting chondrocyte growth and cartilage regeneration, but its delivery has been limited to injections. Continuous PDRN delivery is crucial for effective cartilage regeneration. This study explores using gelatin methacrylate (gelMA) hydrogel, crosslinked with visible light and riboflavin 5′-phosphate sodium (RF) as a photoinitiator, for sustained PDRN release. GelMA hydrogel’s synthesis was confirmed through spectrophotometric techniques, demonstrating successful methacrylate group incorporation. PDRN-loaded gelMA hydrogels displayed varying pore sizes, swelling ratios, degradation rates, and mechanical properties based on gelMA concentration. They showed sustained PDRN release and biocompatibility, with the 14% gelMA-PDRN composition performing best. Glycosaminoglycan (GAG) activity was higher in PDRN-loaded hydrogels, indicating a positive effect on cartilage formation. RT-PCR analysis revealed increased expression of cartilage-specific genes (COL2, SOX9, AGG) in gelMA-PDRN. Histological assessments in a rabbit cartilage defect model demonstrated superior regenerative effects of gelMA-PDRN hydrogels. This study highlights the potential of gelMA-PDRN hydrogels in cartilage tissue engineering, providing a promising approach for effective cartilage regeneration. Full article

Background: Stem cells are capable of self-renewal and differentiation into various specialized cells, making them a potential therapeutic option in regenerative medicine. This study establishes a comprehensive methodology for isolating, culturing, and characterizing rat hair follicle stem cells. Methods and Results: Hair follicles were harvested from Sprague–Dawley rats and subjected to two different isolation techniques. Immunohistochemical analysis and real-time PCR confirm the expression of specific surface markers and genes, validating the cells’ identity. Growth kinetics, colony formation units (CFU), and tri-differentiation capacity were also assessed. Additionally, the cells’ secretome was analyzed, regarding its content in biofactors with wound healing properties. Conclusions: These findings highlight the potential of these cells as a valuable cell source for skin regeneration applications. They contribute to advancing our understanding of stem cell applications in regenerative medicine and hold promise for therapeutic interventions in various clinical contexts, aligning with broader research on the diverse capabilities of hair follicle stem cells. Full article

The abundance of hyaluronic acid (HA) in human tissues attracts its thorough research in tissue regenerating scaffolds and 3D bioprintable hydrogel preparation. Though methacrylation of HA can lead to photo-crosslinkable hydrogels, the catalyst has toxicity concerns, and the hydrogel is not suitable for creating stable complex 3D structures using extrusion 3D bioprinting. In this study, a dual crosslinking on methacrylated HA is introduced, using cysteamine-grafted HA and varying concentrations of 2-hydroxy ethyl acrylate. The resultant hydrogel is suitable for extrusion 3D printing (or bioprinting), mechanically robust, self-standing, stable in phosphate-buffered saline at 37 °C for more than 42 days, has high water absorption capacity with a low swelling ratio (1.5), and exhibits self-healing and adhesive properties. Complex 3D structures like ears and pyramid shapes with more than 2 cm of height are 3D printed using the optimized composition. All the synthesized hydrogels have shown nontoxicity and cell-supportiveness. Loading of cells, tetracycline, and bovine serum albumin into the hydrogel led to better bioink properties such as cell attachment, growth, and proliferation for osteoblast cells. The test results suggest that this hydrogel is biocompatible and has potential for 3D bioprinting of self-standing structures in bioink form in tissue engineering and regenerative medicine. Full article

Regenerative medicine amalgamates stem cell technology and tissue engineering strategies to replace tissues and organs damaged by injury, aging, ailment, and/or chronic conditions by leveraging the innate self-healing mechanism of the body. The term ‘regenerative medicine’ was coined by William A. Haseltine during a 1999 conference on Lake Como. Since its inception in 1968, the field has offered clinical benefits for the regeneration, repair, and restoration of bones, skin, cartilage, neural tissue, and the heart, as well as scaffold fabrication. The field of tissue engineering and regenerative medicine can vastly benefit from advancements in nanoscience and technology, particularly in the fabrication and application of inorganic-based nanoparticles and bionanomaterials. Due to the tunable intrinsic properties, i.e., size, topography, surface charge, and chemical stability, inorganic-based nanoparticles and biomaterials have surpassed traditional synthetic materials. Given the wide gamut of near-future applications of inorganic nanoparticles and biomaterials, this article gives an overview of the emerging roles in stem cell regenerative research, tissue engineering, artificial skin and cartilage regeneration, neural nerve injuries, 3D bioprinting, and development of new inorganic bio-scaffolds. The review also addresses the challenges related to the clinical application and tissue compatibility of inorganic nanoparticles and biomaterials, utilizing current state-of-the-art techniques. Full article

As dental pulp contains the stem cells necessary for regeneration, the tooth should hold the intrinsic capacity for self-repair. A triphasic hybrid dental biocomposite (3HB) composed of biocompatible biopolymers to provide strength, antibacterial properties and protein-based cell support could provide a conducive microenvironment for the regeneration of dental structures. 3HB was incorporated into Mineral Trioxide Aggregate (ProRoot MTA) to construct a malleable injectable implant. Human tooth pulp cells (hDPCs) significantly increased proliferation in the presence of 3HB+MTA compared to 3HB or MTA alone. Cell viability decreased with MTA alone but increased with 3HB and 3HB+MTA. 3HB+MTA was implanted into the residual tooth of drilled Wistar rat M2 molars for up to 45 days. Stereological analysis from micro-CT images showed the volume of the tooth remaining. Histologically, regenerative pulpal architecture was seen invading 3HB. A continuous odontoblastic profile lined a deposit of dentin-like material suggesting reparative dentinogenesis. Overall, no infection or encapsulation was seen. Immunohistochemically, odontoblasts were seen along the margins of the wounded tooth undergoing repair. Mesenchymal cells (MSCs) were seen at the base of the drilled tooth and by 21 days had translocated into the implant itself. Cells stimulating remineralization were highly expressed in the tooth undergoing repair. CD146-positive MSCs were seen in the center of the implant, possibly stimulating remineralization. In conclusion, behavior of 3HB⁺ in vitro and in vivo provided a promising start as 3HB+MTA may serve as a viable regenerative scaffold for pulp regeneration; however, this should be further studied before clinical use can be considered. Full article

Rotator cuff tears (RCT) are the most common cause of shoulder pain among adults. “Rotator cuff” refers to the four muscles that cover the shoulder joint: supraspinatus, infraspinatus, subscapularis, and teres minor. These muscles help maintain the rotational movement and stability of the shoulder joint. RCT is a condition in which one or more of these four muscles become ruptured or damaged, causing pain in the arms and shoulders. RCT results from degenerative changes caused by chronic inflammation of the tendons and consequent tendon tissue defects. This phenomenon occurs because of the exhaustion of endogenous tendon stem cells. Tendon regeneration requires rejuvenation of these endogenous tendon stem/progenitor cells (TSPCs) prior to their growth phase. TSPCs exhibit clonogenicity, multipotency, and self-renewal properties; they express classical stem cell markers and genes associated with the tendon lineage. However, specific markers for TSPC are yet to be identified. In this review, we introduce novel TSPC markers and discuss various strategies for TSPC reprogramming. With further research, TSPC reprogramming technology could be adapted to treat age-related degenerative diseases, providing a new strategy for regenerative medicine. Full article