Adipose‐derived stromal vascular fraction (SVF)‐gel has an autologous origin and favorable immunocompatibility and exhibits favorable safety and efficacy in facilitating cartilage regeneration and repair.
Abstract
Osteoarthritis (OA), a prevalent degenerative joint disorder, is suboptimally managed by existing treatments owing to adverse effects, limited therapeutic efficacy, and the inability to achieve genuine cartilage repair. Adipose‐derived stromal vascular fraction (SVF)‐gel, which is abundant in stem cells and bioactive factors, has an autologous origin and favorable immunocompatibility and exhibits favorable safety and efficacy in facilitating cartilage regeneration and repair. Building upon prior research, this review discusses the clinical efficacy and potential of SVF‐gel, while also recognizing challenges such as the standardization of preparation procedures and dosage optimization. Future research ought to concentrate on integrating advanced technologies, including gene editing, artificial intelligence (AI), and nanomaterials, to drive its development towards more precise and personalized therapeutic approaches.
Osteoarthritis (OA) is a common degenerative joint disease characterized by pain, stiffness, progressive cartilage loss, and reduced mobility. Current treatments primarily aim to relieve symptoms rather than restore damaged cartilage, and durable regeneration of native hyaline cartilage remains a major clinical challenge. Extracellular Vesicles (EVs), particularly those derived from Mesenchymal Stem Cells (MSCs), have emerged as promising cell-free therapeutic platforms because of their ability to modulate inflammation, regulate chondrocyte activity, and influence extracellular matrix metabolism. However, EV heterogeneity, source-dependent variability, limited targeting efficiency, inconsistent cargo loading, and lack of standardized manufacturing protocols continue to restrict their clinical translation. This review summarizes recent advances in engineered EV-based strategies for OA and cartilage repair, including parental-cell preconditioning, genetic modification, surface functionalization, cargo loading, artificial EV platforms, and biomaterial-assisted delivery. Importantly, we distinguish between in vitro findings, preclinical animal studies, and early clinical evidence to provide a balanced assessment of translational readiness. We also discuss key regulatory and safety challenges, including GMP-compliant production, batch-to-batch variability, quality-control criteria, potency assays, scalability, biodistribution, and long-term safety. By integrating EV engineering with translational and regulatory perspectives, this review highlights the potential of engineered EVs as future disease-modifying tools for OA while emphasizing that their clinical efficacy and capacity to restore durable hyaline cartilage remain to be demonstrated in robust human studies.
Shayan Boozarjomehri Amnie, Sina Mahmoudian, Mahdi Ghorbani et al.· Avicenna journal of medical...· 0 citations
Cartilage is susceptible to degeneration from injury, overuse, or age-related wear. Articular cartilage, the smooth hyaline cartilage covering the ends of bones in synovial joints, has limited intrinsic repair capacity because its avascular, aneural, and alymphatic matrix contains sparse, low-proliferative chondrocytes, allowing matrix damage to persist and drive joint dysfunction and osteoarthritis. Most therapies relieve symptoms without reliably restoring durable cartilage architecture. Recent advances in cell-based therapy, matrix-associated chondrocyte implantation, engineered scaffolds, controlled-release biologics, and quantitative clinical endpoints have shifted the field toward mechanism-based cartilage regeneration. In this feature review, we assess emerging clinical evidence across cell-based strategies, biomaterial- and scaffold-assisted repair, biologics, and combination approaches. We emphasize integrated, multimodal approaches and standardized outcome measures as essential for achieving durable cartilage repair and true disease modification.
Cindy A. Thomas-Charles, Raymond Xue, A. Agosto et al.· Trends in Molecular Medicine· 0 citations
Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by progressive cartilage destruction, chronic inflammation, pain, and functional impairment. Conventional therapies primarily focus on symptom management and are unable to restore damaged articular cartilage or effectively modify disease progression. Consequently, increasing attention has been directed toward biologic and regenerative approaches that target the underlying mechanisms of cartilage degeneration and joint dysfunction. This review provides a comprehensive overview of emerging regenerative strategies for articular cartilage repair, including gene- and noncoding RNA-based therapies, platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), mesenchymal stromal cells (MSCs), MSC-derived exosomes, and cell-based interventions. Current evidence indicates that these therapies exert their effects through modulation of inflammatory pathways, enhancement of extracellular matrix synthesis, promotion of chondrocyte survival, and regulation of tissue repair processes. Among them, PRP and BMAC offer minimally invasive approaches with favorable safety profiles, whereas MSCs and exosome-based therapies demonstrate substantial regenerative and immunomodulatory potential. Gene and epigenetic therapies further provide opportunities to target disease-associated molecular pathways and improve cartilage homeostasis. Despite encouraging preclinical and clinical outcomes, significant challenges remain, including heterogeneity in biologic preparations, variability in treatment protocols, limited long-term clinical evidence, and the absence of standardized outcome measures. Future research should focus on mechanistic validation, protocol standardization, optimization of delivery strategies, and large-scale randomized clinical trials to establish the long-term safety and disease-modifying efficacy of these regenerative therapies. Collectively, biologic and regenerative interventions represent promising avenues for advancing cartilage repair and improving clinical outcomes in patients with osteoarthritis.
Haiyuan Yue, Ahmad Alhaskawi, S. Ezzi et al.· Frontiers in Pharmacology· 0 citations
Osteoarthritis (OA) is multifactorial degenerative joint diseases with high incidence and heavy burden on human health and the world economy. Conventional approaches to combat OA have certain therapeutic efficacy. However, these treatments can inadvertently harm healthy tissues and lead to various complication. Biomaterials have emerged as a promising alternative due to their enhanced effectiveness, precise targeting, and spatiotemporal controllability. Despite these benefits, synthetic biomaterials - particularly inorganic nanomaterials used as drug delivery vehicles or direct therapeutic agents (e.g., ROS-scavenging nanozymes, lubricants, and photothermal platforms) - still face challenges such as rapid synovial clearance, limited cartilage penetration, and potential biocompatibility concerns, which have impeded their broader clinical application in OA treatment. To address these limitations, cell-based biomaterials leverage the intrinsic properties of cells-such as chemotaxis, homing ability, and biocompatibility-to design advanced therapeutic systems tailored for joint microenvironments. In this review, we first provide an analysis of OA abnormalities, including biophysical, cellular, and biochemical aspects. Then, we describe the design principles of cell-based biomaterials based on these abnormalities. Afterwards, we summarize various varieties of cell-based biomaterials and the recent advances of their applications in OA treatment. Finally, we explore the current challenges and prospects of cell-based biomaterials.
Osteoarthritis (OA), a prevalent chronic degenerative joint disorder, affects hundreds of millions of people worldwide and has become a leading cause of joint pain and functional impairment in middle-aged and elderly populations. It not only severely compromises patients’ quality of life but also imposes a significant socioeconomic burden on public health systems. Targeting key pathological processes in OA, such as inflammatory responses, chondrocyte apoptosis, and dysregulated autophagy, an injectable liposomal system named RAPA@Lipo/rhCol Ⅲ were developed in this study. This system consisted of rapamycin-loaded liposomes surface-modified with recombinant human collagen type Ⅲ (rhCol Ⅲ). It enabled sustained release of rapamycin to precisely inhibit the mTOR pathway, thereby exerting synergistic biological effects including anti-inflammation, inhibition of chondrocyte apoptosis, and promotion of autophagy. Moreover, the surface collagen modification enhanced the system’s biocompatibility and provided essential matrix microenvironment cues and bioactive signals for cartilage repair. Experimental results demonstrated that RAPA@Lipo/rhCol Ⅲ effectively scavenged reactive oxygen species in chondrocytes, promoted cell proliferation and cartilage matrix synthesis, and modulated the expression of autophagy- and inflammation-related genes, thereby synergistically achieving structural and functional restoration of OA cartilage across multiple dimensions. The integrated “disease modulation-tissue repair” strategy proposed in this study offerd a novel approach and experimental evidence for targeted therapy and functional regeneration in osteoarthritis.
Chenxin Liu, Wenling Dai, Xingchen Zhao et al.· Collagen and Leather· 0 citations
Chronic tendinopathy is a debilitating tendon overuse disorder characterized by localized tenderness, swelling, and pain, significantly impairing physical function. It is particularly common among the overuse and aging populations. Traditional treatment options, including conservative therapies and surgical interventions, often yield limited success. Recent studies indicate that extracellular vesicles (EV) derived from stem cells provide a promising therapeutic avenue for healing of tendon and tendon-to-bone junction (TBJ) injuries associated with chronic tendinopathy. Their unique properties, such as higher cargo stability and the ability to serve as carriers for targeted drug delivery, position them as ideal candidates for tendinopathy treatment. However, the low yield of EVs presents challenges for clinical applications. This review systematically review various strategies to enhance EV yield and function, including preconditioning stem cells through biophysical, biological, or chemical means; genetic engineering of stem cells; in vitro loading of proteins or drugs and surface modification of EVs; and modifying the stem cell culture environment, particularly through three-dimensional (3D) culture techniques. Emphasis is placed on scaffold-free methods, scaffold-based methods, 3D printing, spinner flasks, and bioreactors, which can potentially improve EV yield and functions for tendon and TBJ regeneration. The review also summarizes relevant preclinical data and explores the molecular mechanisms underlying enhanced EV yield and functions, as well as the mechanisms of EVs on tendon and TBJ repair. Future research directions include investigating various EV enhancement strategies in models of degenerative tendon injury, studying the underlying molecular mechanisms, establishing cost-effective methods for scalable EV production, optimizing EV treatment protocols for clinical translation, and exploring combination strategies to enhance therapeutic EV production and function.
Haining Liu, P. P. Lui· Stem cell research & therape...· 0 citations
