Search Results (300)

Focal chondral defects of the knee are a common cause of pain and functional limitation in active individuals and may predispose to early degenerative joint changes. Given the limited regenerative capacity of hyaline cartilage, biologically based surgical strategies have emerged to promote tissue repair and restore joint function. This narrative review critically examines current treatment approaches that rely on autologous cell sources and scaffold-supported regeneration. Particular emphasis is placed on techniques that stimulate endogenous repair or support chondrocyte-based tissue restoration through the use of autologous biomaterial constructs. The influence of lesion morphology, joint biomechanics, and patient-specific variables on treatment selection is discussed in detail, focusing on the differences between tibiofemoral and patellofemoral involvement. Biologically driven approaches have shown promising mid- to long-term outcomes in selected patients, and are increasingly favoured over traditional methods in specific clinical scenarios. However, the literature remains limited by heterogeneity in study design, follow-up duration, and outcome measures. This review aims to provide an evidence-based, morphology-informed framework to support the clinical decision-making process in the management of knee cartilage defects. Full article

Platelet-rich plasma (PRP) is widely used in regenerative medicine, yet clinical outcomes remain inconsistent. While traditional strategies have focused on platelet concentration and activation methods, emerging evidence suggests that the biological age of platelets, especially platelet senescence, may be a critical but overlooked factor influencing therapeutic efficacy. Senescent platelets display reduced granule content, impaired responsiveness, and heightened pro-inflammatory behavior, all of which can compromise tissue repair and regeneration. This review explores the mechanisms underlying platelet aging, including oxidative stress, mitochondrial dysfunction, and systemic inflammation, and examines how these factors influence PRP performance across diverse clinical contexts. We discuss the functional consequences of platelet senescence, the impact of comorbidities and aging on PRP quality, and current tools to assess platelet functionality, such as HLA-I–based flow cytometry. In addition, we present strategies for pre-procedural optimization, advanced processing techniques, and adjunctive therapies aimed at enhancing platelet quality. Finally, we challenge the prevailing emphasis on high-volume blood collection, highlighting the limitations of quantity-focused protocols and advocating for a shift toward biologically precise, function-driven regenerative interventions. Recognizing and addressing platelet senescence is a key step toward unlocking the full therapeutic potential of PRP-based interventions. Full article

The combination of scaffold materials and bioactive factors is a promising strategy for promoting bone defect repair in tissue engineering. Previous studies have shown that osteoglycin (OGN) is highly expressed in the bone repair process using deer antler as an animal model of bone defects. It suggests that OGN may be a key active component involved in the bone repair process. The aim of this study was to investigate whether deer OGN (dOGN) could effectively promote bone regeneration. We successfully expressed dOGN using the E. coli pET30a system and evaluated its biological activity through cell proliferation and migration assays. At a concentration of 5 μg/mL, dOGN significantly promoted cell proliferation and migration. We then incorporated dOGN onto decellularized antler cancellous bone (DACB) scaffolds and assessed their osteogenic potential both in vitro and in vivo. The results indicated that dOGN loading enhanced cell proliferation, adhesion, and osteogenic activity. In vivo experiments confirmed that the dOGN-DACB scaffold significantly improved bone regeneration compared to DACB alone. This study demonstrates that dOGN-loaded DACB scaffolds hold great potential for clinical applications in treating critical-sized bone defects by mimicking the rapid regenerative properties of deer antlers. Full article

Tissue-engineered scaffolds, particularly composite scaffolds composed of polymers combined with ceramics, bioactive glasses, or nanomaterials, play a vital role in regenerative medicine by providing structural and biological support for tissue repair. As scaffold designs grow increasingly complex, the need for non-invasive imaging modalities capable of monitoring scaffold integration, degradation, and tissue regeneration in real-time has become critical. This review summarizes current non-invasive imaging techniques used to evaluate tissue-engineered constructs, including optical methods such as near-infrared fluorescence imaging (NIR), optical coherence tomography (OCT), and photoacoustic imaging (PAI); magnetic resonance imaging (MRI); X-ray-based approaches like computed tomography (CT); and ultrasound-based modalities. It discusses the unique advantages and limitations of each modality. Finally, the review identifies major challenges—including limited imaging depth, resolution trade-offs, and regulatory hurdles—and proposes future directions to enhance translational readiness and clinical adoption of imaging-guided tissue engineering (TE). Emerging prospects such as multimodal platforms and artificial intelligence (AI) assisted image analysis hold promise for improving precision, scalability, and clinical relevance in scaffold monitoring. Full article

Gene therapy is a groundbreaking strategy in regenerative medicine, enabling precise cellular behavior modulation for tissue repair. In situ nucleic acid delivery systems aim to directly deliver nucleic acids to target cells or tissues to realize localized genetic reprogramming and avoid issues like donor cell dependency and immune rejection. The key to success relies on biomaterial-engineered delivery platforms that ensure tissue-specific targeting and efficient intracellular transport. Viral vectors and non-viral carriers are strategically modified to enhance nucleic acid stability and cellular uptake, and integrate them into injectable or 3D-printed scaffolds. These scaffolds not only control nucleic acid release but also mimic native extracellular microenvironments to support stem cell recruitment and tissue regeneration. This review explores three key aspects: the mechanisms of gene editing in tissue repair; advancements in viral and non-viral vector engineering; and innovations in biomaterial scaffolds, including stimuli-responsive hydrogels and 3D-printed matrices. We evaluate scaffold fabrication methodologies, nucleic acid loading–release kinetics, and their biological impacts. Despite progress in spatiotemporal gene delivery control, challenges remain in balancing vector biocompatibility, manufacturing scalability, and long-term safety. Future research should focus on multifunctional “smart” scaffolds with CRISPR-based editing tools, multi-stimuli responsiveness, and patient-specific designs. This work systematically integrates the latest methodological advances, outlines actionable strategies for future investigations and advances clinical translation perspectives beyond the existing literature. Full article

Tissue engineering is a growing field with multidisciplinary players in cell biology, engineering, and medicine, aiming to maintain, restore, or enhance functions of tissues and organs. The extracellular matrix (ECM) plays fundamental roles in tissue development, maintenance, and repair, providing not only structural support, but also critical biochemical and biomechanical cues that regulate cell behavior and signaling. Although its specific composition varies across different tissue types and developmental stages, matrix molecules influence various cell functional properties in every tissue. Given the importance of ECM in morphogenesis, tissue homeostasis, and regeneration, ECM-based bioscaffolds, developed through tissue engineering approaches, have emerged as pivotal tools for recreating the native cellular microenvironment. The aim of this study is to present the main categories of these scaffolds (i.e., natural, synthetic, and hybrid), major fabrication techniques (i.e., tissue decellularization and multidimensional bioprinting), while highlighting the advantages and disadvantages of each category, focusing on biological activity and mechanical performance. Scaffold properties, such as mechanical strength, elasticity, biocompatibility, and biodegradability are essential to their function and integration into host tissues. Applications of ECM-based bioscaffolds span a range of engineering and regenerative strategies, including cartilage, bone, cardiac tissue engineering, and skin wound healing. Despite promising advances, challenges remain in standardization, scalability, and immune response modulation, with future directions directed towards improving ECM-mimetic platforms. Full article

Plasma-derived fibrin hydrogels are widely used in tissue engineering because of their excellent biological properties. Specifically, human plasma-derived fibrin hydrogels serve as 3D matrices for autologous skin graft production, skeletal muscle repair, and bone regeneration. Nevertheless, for advanced applications such as in vitro skin equivalents and engineered grafts, the intrinsic limitations of native fibrin hydrogels in terms of long-term mechanical stability and resistance to degradation need to be addressed to enhance the usefulness and application of these hydrogels in tissue engineering. In this study, we chemically modified plasma-derived fibrin by incorporating succinimidyl alginate (SA), a version of alginate chemically modified to introduce reactive succinimidyl groups. These NHS ester groups (N-hydroxysuccinimide esters), attached to the alginate backbone, are highly reactive toward the primary amine groups present in plasma proteins such as fibrinogen. When mixed with plasma, the NHS groups covalently bond to the amine groups in fibrin, forming stable amide linkages that reinforce the fibrin network during hydrogel formation. This chemical modification improved mechanical properties, reduces contraction, and enhanced the stability of the resulting hydrogels. Hydrogels were prepared with a final fibrinogen concentration of 1.2 mg/mL and SA concentrations of 0.5, 1, 2, and 3 mg/mL. The objective was to evaluate whether this modification could create a more stable matrix suitable for supporting skin tissue development. The mechanical and microstructure properties of these new hydrogels were evaluated, as were their biocompatibility and potential to create 3D skin models in vitro. Dermo-epidermal skin cultures with primary human fibroblast and keratinocyte cells on these matrices showed improved dermal stability and better tissue structure, particularly SA concentrations of 0.5 and 1 mg/mL, as confirmed by H&E (Hematoxylin and Eosin) staining and immunostaining assays. Overall, these results suggest that SA-functionalized fibrin hydrogels are promising candidates for creating more stable in vitro skin models and engineered skin grafts, as well as for other types of engineered tissues, potentially. Full article

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

Repairing and regenerating tissue barriers is a key challenge in regenerative medicine. Stem cells play a crucial role in restoring the structural and functional integrity of key epithelial barrier surfaces, including the skin and mucosa. This review analyzes the role of dental pulp stem cells (DPSCs) and their derivatives, including extracellular vesicles, conditioned medium, and intracellular factors, in accelerating skin wound healing. The key mechanisms include: (1) DPSCs regulating inflammatory microenvironments by promoting anti-inflammatory M2 macrophage polarization; (2) DPSCs activating vascular endothelial growth factor (VEGF) to drive angiogenesis; (3) DPSCs optimizing extracellular matrix (ECM) spatial structure through matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) balance; and (4) DPSCs enhancing transforming growth factor-β (TGF-β) secretion to accelerate granulation tissue formation. Collectively, these processes promote wound healing. In addition, we explored potential factors that accelerate wound healing in DPSCs, such as oxidative stress, mechanical stimulation, hypertension, electrical stimulation, and organoid modeling. In addition to demonstrating the great potential of DPSCs for skin repair, this review explores their translational prospects in mucosal regenerative medicine. It covers the oral cavity, esophagus, colon, and fallopian tube. Some studies have found that combining DPSCs and their derivatives with drugs can significantly enhance their biological effects. By integrating insights from skin and mucosal models, this review offers novel ideas and strategies for treating chronic wounds, inflammatory bowel disease, and mucosal injuries. It also lays the foundation for connecting basic research results with clinical practice. This represents a significant step forward in tackling these complex medical challenges and lays a solid scientific foundation for developing more targeted and efficient regenerative therapies. Full article

Background/Objectives: Complete rupture of the Achilles tendon is a common and challenging injury, specifically for individuals engaged in high-demand activities such as sports. Surgical repair is often required, but conventional methods, including direct suture repair, may fail to address the biological limitations associated with tendon healing, especially in cases involving chronic degeneration or extensive tissue damage. Methods: This case report explains how bioinductive implants, such as the Regeneten collagen-based scaffold, have gained attention as an innovative approach to augment tendon repair. Results: These implants not only provide mechanical stabilization but also promote the regeneration of tendon-like tissue by enhancing the biological healing environment. Conclusions: The use of bioinductive implants, such as the Regeneten scaffold, improves outcomes in tendon repair by augmenting both mechanical stabilization and biological healing. This approach represents a valuable alternative to improve clinical outcomes, particularly in patients with poor prognostic factors. Full article

By stimulating living tissues with proper molecules, the angiogenesis and vasculogenesis processes can be observed. Prostaglandin E1 (PGE1), which is a molecule that widens blood vessels and which is used for several medical purposes, such as treating critical limb ischemia, is a typical leading molecule in angiogenesis studies. Nevertheless, its involvement in vasculogenesis and morphogenesis is a more specific subject in the field of developmental biology and therapeutic research. Vasculogenesis is the embryonic phenomenon in which endothelial progenitor cells generate new blood vessels. This phenomenon is distinct and divergent from angiogenesis, which entails the creation of novel blood vessels extending from pre-existing ones. Morphogenesis is the biological phenomenon responsible for the development of an organism or its components into a specific shape. Embryonic development and tissue regeneration are essential components. Current research is investigating the broader consequences of prostaglandins, such as PGE1, in the fields of developmental biology and regenerative medicine. Gaining knowledge about the impact of PGE1 on morphogenesis could provide valuable insights into congenital vascular abnormalities and innovative approaches for tissue repair and regeneration, especially in limb ischemia. In this study, a histologic and morphogenesis study was carried out on Artemia salina napi (first stage of development) by simulating the angiogenesis and morphogenesis processes using PGE1 as the top molecule with vasoactive properties and a series of benopyridyne (3-aminoquinolines, 5-amino quinolines, 8-aminoquinolines, 8-hydroxyquinolines and quinolines, respectively). A series of 30 Artemia salina napi were exposed to the compound listed before. Also, a lot of 30 unexposed Artemia salina napi was taken into account. In total, 210 Artemia salina napi were studied as a model for angionensis and morphogenesis. The study used wet experiments together with imaging reconstruction and graph-generating methodologies. The results show that PGE1 can initiate the shape of the vessel formation. Also, some quinoline series have a pro-mild morphogenetic and angiogenetic effect. Overall, PGE1 plays a significant role in mediating vasculogenesis and morphogenesis through its vasodilatory, anti-inflammatory, and pro-proliferative effects on endothelial cells. PGE1 is involved mainly in increasing the length of the vessel, while the number of vascular branching has an all-simulating general impact. However, the molecules with mild vasculogenic effects tend to develop more complex, limited vascular networks, having a more localized role in the angiogenetic process. Overall imaging and graph analysis showed significant and distinct properties of the vascular network-derived graph. Full article

Background/Objectives: Chronic illness after COVID-19 vaccination (longvax) lacks a therapeutic protocol anchored in pathophysiology. Persistent vaccine derived spike protein appears to trigger microvascular fibrin amyloid microclots, immune dysfunction, pathogen reactivation and multisystem injury. This article proposes an integrative approach, Vaxtherapy, to tackle these mechanisms. Methods: A narrative synthesis of peer reviewed literature from 2021 to 2025 on spike related injury and vaccine adverse events was conducted, supplemented by clinical case series and mechanistic observations from long COVID. The findings were arranged into a four stage therapeutic sequence ordered by pathophysiological precedence. Results: Stage one aims to reopen hypoperfused tissue through oral fibrinolytics that degrade fibrin amyloid resistant microclots; stage two intends to neutralise circulating or tissue bound spike via a receptor binding domain monoclonal antibody cocktail; stage three seeks to eliminate reactivated viral or microbial reservoirs with targeted antivirals or antimicrobials once perfusion is improved; and stage four aspires to support tissue repair with mitochondrial supplements and, when indicated, cell based therapies. Omitting or reordering stages may reduce efficacy or foster resistance. Conclusions: This hypothesis driven framework outlines a biologically plausible roadmap for longvax research. By matching interventions to specific mechanisms (fibrinolysis, spike neutralisation, pathogen clearance and regeneration), it aims to guide controlled trials and compassionate pilot programs directed at durable recovery rather than chronic symptom management. Full article

Wound healing is a complex biological process that involves the regulation of reactive oxygen species (ROS), which play a critical role in cellular signaling and tissue repair. While the dual nature of ROS means that maintaining controlled levels is essential for effective wound healing, excessive ROS production can hinder the recovery process. Bioactive compounds represent promising therapeutic candidates enriched with polyphenols, which are known for their high therapeutic properties and minimal adverse effects, and are thus highlighted as promising therapeutic candidates for wound healing due to their antioxidant properties. However, their clinical application is often limited due to challenges such as poor solubility and low bioavailability. To overcome this, the encapsulation of these compounds into nanocarriers has been proposed, which enhances their stability, facilitates targeted delivery, and allows for controlled release. The present review highlights emerging innovations in nanomedicine-based drug delivery of natural antioxidants for precise modulation of ROS in wound healing. Moreover, the review elaborates briefly on various in vitro and in vivo studies that assessed the ROS levels using different fluorescent dyes. By modulating ROS levels and improving the local microenvironment at wound sites, these bioactive-nanomedicine formulations can significantly accelerate the healing process of wounds. The review concludes by advocating for further research into optimizing these nano-formulations to maximize their potential in clinical settings, thereby improving therapeutic strategies for wound care and regeneration. Full article

Wound healing is a complex biological process that benefits from advanced biomaterials capable of modulating inflammation and promoting tissue regeneration. In this study, cerium oxide nanoparticles (CeO₂NPs) were green-synthesized using Hemerocallis citrina extract, which served as both a reducing and stabilizing agent. The CeO₂NPs exhibited a spherical morphology, a face-centered cubic crystalline structure, and an average size of 9.39 nm, as confirmed by UV-Vis spectroscopy, FTIR, XRD, and TEM analyses. These nanoparticles demonstrated no cytotoxicity and promoted fibroblast migration, while significantly suppressing the production of inflammatory mediators (TNF-α, IL-6, iNOS, NO, and ROS) in LPS-stimulated RAW264.7 macrophages. Gene expression analysis indicated M2 macrophage polarization, with upregulation of Arg-1, IL-10, IL-4, and TGF-β. Aligned polycaprolactone/polylactic acid (PCL/PLA) nanofibers embedded with CeO₂NPs were fabricated using electrospinning. The composite nanofibers exhibited desirable physicochemical properties, including porosity, mechanical strength, swelling behavior, and sustained cerium ions release. In a rat full-thickness wound model, the CeO₂ nanofiber-treated group showed a 22% enhancement in wound closure compared to the control on day 11. Histological evaluation revealed reduced inflammation, enhanced granulation tissue, neovascularization, and increased collagen deposition. These results highlight the therapeutic potential of CeO₂-incorporated nanofiber scaffolds for accelerated wound repair and inflammation modulation. Full article

Plantar fasciitis is a common condition characterized by inflammation and degeneration of the plantar fascia, leading to heel pain and reduced mobility. Affecting both athletic and non-athletic populations, it is a leading cause of foot-related medical visits. Conservative treatments, including rest, physical therapy, and corticosteroid injections, provide relief for most patients, but a subset experiences persistent symptoms requiring advanced therapies. Emerging biologic treatments, such as platelet-rich plasma (PRP) and mesenchymal stem/stromal cell (MSC) therapy, have demonstrated potential in promoting tissue regeneration and reducing inflammation. Recently, MSC-derived extracellular vesicles (MSC-EVs) have gained attention for their regenerative properties, offering a promising, cell-free therapeutic approach. EVs mediate tissue repair through immunomodulation, anti-inflammatory signaling, and extracellular matrix stabilization. Preclinical studies suggest that EV therapy may improve tendon and ligament healing by promoting M2 macrophage polarization, inhibiting excessive metalloproteinase activity, and enhancing vascular remodeling. This review explores the potential of MSC-EVs as an innovative, non-surgical treatment for plantar fasciitis, addressing their mechanisms of action and current evidence in musculoskeletal regeneration. Full article