From human joints to bioreactor setups: Quantifying mechanical stimuli in cartilage physiology and regeneration.

Engineering the cartilage niche: Mimicking the microenvironment for functional outcomes.

Microsphere-embedded dual-network hydrogel with fatigue resistance, drug release, and chondrogenesis for potential cartilage repair.

Kartogenin-Loaded Selenium-Prussian Blue Nanogel through ROS scavenging and cartilage regeneration for the mitigation of osteoarthritis.

Methods and strategies of bioengineered cell exosomes for the treatment of osteoarthritis.

Semaglutide alleviates osteoarthritis independent of weight loss via GLP-1R-mediated activation of autophagy through AKT/mTOR inhibition.

It was found that pressure can promote the regeneration and repair of cartilage defects based on bone marrow mesenchymal stem cells (BMSCs). Since the compressive microenvironment of the cartilage in vivo may change with different movement, the mechanobiological effects of different compressive condition on BMSCs, especially the impact for its chondrogenic differentiation and influence on the cartilage microenvironment, is what we concerned about. Rat BMSCs were cultured and subjected to various types of pressure stimulation for 1h. The Cell Counting Kit-8 (CCK-8) assay was used to analyze cell proliferation, flow cytometry was employed to assess the cell cycle and apoptosis, confocal microscopy was used to observe the cytoskeleton, and transmission electron microscopy was performed to examine the cellular ultrastructure. RT-PCR was used to identify chondrogenic differentiation markers. Apoptotic vesicles derived from BMSCs were isolated by ultracentrifugation, and differentially expressed microRNAs in these vesicles under - 40kPa compression were identified by transcriptome sequencing. Specific pressure conditions promoted the proliferation of BMSCs, with dynamic pressure showing a stronger proliferative effect than static pressure. Higher static negative pressure (- 40kPa) significantly increased the spreading area of BMSCs. Dynamic pressure is stronger than static pressure in promoting cytoskeletal rearrangement, stress fiber formation, and cartilage marker expression in BMSCs. Flow cytometry and transmission electron microscopy results show that both - 40kPa static and 90kPa dynamic pressures promote BMSCs apoptosis to some extent. Under - 40kPa static negative pressure, the differentially expressed microRNAs in BMSCs-derived apoptotic vesicles are involved in stem cell maintenance and chondrogenic proliferation processes. Static negative pressure (- 40kPa) induces apoptosis in bone marrow mesenchymal stem cells (BMSCs). Notably, compared to chemical induction with staurosporine (STS), BMSCs subjected to - 40kPa mechanical stimulation display distinct microRNA expression profiles within apoptotic vesicles, specifically enriched in microRNAs implicated in stem cell fate determination and cartilage regeneration. These findings offer valuable insights into biomechanical strategies for optimizing tissue-engineered cartilage repair.

Thermo-responsive Hydroxybutyl-chitosan hydrogel for oxidative stress modulation and cartilage regeneration in temporomandibular joint osteoarthritis

Alginate-calcium composites: advances in design, functional properties, and applications in biomedicine and environmental remediation.

The development of biomimetic scaffolds capable of promoting both cartilage and subchondral bone regeneration remains a major challenge in osteochondral tissue engineering. In this study, type I acid-soluble collagen (ASC) was successfully extracted from black flounder (Paralichthys olivaceus) skin and systematically characterized. The purified ASC retained its native triple-helical structure, as confirmed by SDS-PAGE, FTIR, CD, and XRD analyses, and exhibited favorable self-assembly behavior near physiological pH. Based on this natural matrix, photocrosslinkable methacrylated chondroitin sulfate (CSMA) was synthesized and combined with ASC or mineralized collagen (MC) to fabricate injectable composite hydrogels via UV-initiated polymerization. The resulting CSMA/COL and CSMA/MC hydrogels demonstrated tunable gelation times (90-120 s), high porosity, excellent swelling capacity, and superior mechanical strength (compressive modulus up to ∼40 kPa). Rheological analysis revealed stable viscoelastic properties with G' consistently exceeding G″. The composites also exhibited remarkable self-healing ability. In vitro, all hydrogel extracts displayed outstanding cytocompatibility, promoting primary chondrocyte adhesion, proliferation, and migration. Hydrogels containing collagen and MC (especially CS5M1) significantly enhanced the alkaline phosphatase (ALP) activity and upregulated chondrogenic gene expression (COL II, Acan, and Sox9). In vivo implantation in a rat full-thickness cartilage defect model demonstrated that CSMA-based composite hydrogels facilitated seamless defect filling, enhanced proteoglycan and glycosaminoglycan deposition, and promoted subchondral bone remodeling. Among all formulations, CS5M1 achieved the most complete repair, regenerating hyaline-like cartilage integrated with surrounding tissue after 12 weeks. Collectively, these results demonstrate that the composite hydrogels provide a biomimetic, injectable, and photo-curable platform with excellent osteochondral regenerative potential.

Osteoarthritis (OA) progression is driven by chronic inflammation, oxidative stress, and mitochondrial dysfunction, which together disrupt cartilage homeostasis and hinder regeneration. Here, we developed a paeoniflorin-loaded multifunctional hydrogel (AdHy@Pae) composed of 2-Hydroxyethyl methacrylate, sulfobetaine methacrylate, and sodium polyglutamate. The latter two components endowed the material with excellent adhesive properties, whereas the introduction of Pae provided abundant hydroxyl groups to decrease interfacial energy, resulting in superior lubrication under wet condition. More importantly, with sustained release of Pae and scavenge of ROS, AdHy@Pae alleviated oxidative injury, restored mitochondrial membrane potential, and preserved cell viability of chondrocyte. It also rebalanced extracellular matrix (ECM) metabolism and maintained cartilage phenotypic stability. In a rat OA model, intra-articular administration of AdHy@Pae markedly restored cartilage and subchondral bone architecture, as evidenced by improved trabecular continuity, smooth cartilage surfaces, and significantly reduced OARSI and Mankin scores. Transcriptomic profiling and network analysis revealed that AdHy@Pae reprograms mitochondrial dynamics homeostasis and inflammatory gene networks, notably suppressing IL-17A and TNF-α signaling. Collectively, AdHy@Pae provides a robust and durable strategy for precise cartilage protection and repair in osteoarthritis.

Rotator cuff tears lead to bone loss because of reduced mechanical loading at the tendon-bone interface, which results in poor healing after rotator cuff repair (RCR). Whether Yoda1, the specific Piezo1 agonist, can counteract bone loss and promote rotator cuff healing has not yet been explored. Yoda1 promotes tendon-to-bone healing in a rat model of RCR and regulates M1/M2 macrophage polarization at the tendon-bone interface. Controlled laboratory study. A total of 120 male rats aged 12 weeks, which were randomly divided into 4 groups, were used to establish the RCR model: vehicle-only (control [CON]), low-concentration Yoda1 (LC), moderate-concentration Yoda1 (MC), and high-concentration Yoda1 (HC) intraperitoneal injection. The rats were sacrificed at 4 and 8 weeks. Tendon-to-bone healing at the repair site was evaluated using histological, bone microstructure, and biomechanical analyses. Macrophage polarization was observed through immunofluorescence staining. The LC group showed higher histological scores compared with the CON group at each time point (P < .001). More organized collagen fibers and greater cartilage regeneration were observed in the intervention groups compared with the CON group, as confirmed by immunohistochemistry for collagen type II. Additionally, the LC group exhibited more new bone formation compared to the CON group at 4 weeks (P < .001). Biomechanically, all intervention groups exhibited significantly higher failure loads and stiffness than the CON group at 4 and 8 weeks. In immune regulation, the expression of CD86 was significantly decreased, and CD206 expression was significantly increased, in the intervention groups compared to the CON group at 4 weeks. However, there were no significant differences in the expression of CD86 and CD206 among the groups at 8 weeks. Yoda1 improved tendon-to-bone healing in a rat model of RCR. In addition, Yoda1 promoted the infiltration of M2 macrophages at the repair site, which may have facilitated healing at the tendon-bone interface. The present study is an exploratory investigation. Postoperative treatment using Yoda1 could be a potential therapeutic strategy to improve tendon-to-bone healing in patients with rotator cuff tears.

Articular cartilage (AC) defects can lead to joint destruction and osteoarthritis, necessitating immediate intervention to prevent progressive cartilage degeneration. To support cartilage repair, hydrogels have been explored due to their structural similarity to the extracellular matrix (ECM), offering a hydrated microenvironment for chondrocytes that promotes cell adhesion and proliferation. Polyurethane (PU) is a promising candidate with adjustable mechanical properties, high biocompatibility, and degradability. Given the advantages of both hydrogels and PU for biomedical applications, functional degradable PU hydrogels present a potential solution for cartilage regeneration. This review summarizes the structure-property relationship and degradation mechanisms of PU hydrogels. Their advanced functionalities in cartilage repair are highlighted, including anti-inflammatory and antibacterial properties, controlled drug delivery, injectability, self-healing, and stimulus responsiveness. By reviewing recent advances and emerging technologies, this review provides valuable insights and a future outlook for the development of next-generation cartilage repair materials.

Innovations in ear reconstruction in the developing medical field have resulted in various advantages and disadvantages. In addition to rib autologous ear cartilage reconstruction, cartilage differentiation is achieved using stem cell technologies, or cartilage is constructed using tissueengineering-based systems from various natural and artificial materials. Intercalarily, autologous rib ear cartilage reconstruction is routinely used; it is a field that is constantly being developed, from stem cells and cell culture systems to natural and artificial biomaterials and tissue engineering-based systems. It is estimated that 3D scaffold systems created using tissue engineering approaches will continue to be popular for a long time in terms of both shaping and cellularization. The differentiation potential of stem cells, the mechanical strength, biocompatibility, and biodegradability of scaffolds, and especially the use of exosome engineering as a biosignal molecule, which has become popular recently, bring another perspective on cartilage regeneration. The nanostructures of exosomes carry very important information between cells in terms of their anti-inflammatory activities and especially their effects on the proliferation and differentiation activities of stem cells. Especially modified or loaded exosome designs allow different approaches to be created in this field, both for therapeutics and diagnosis. This review offers a regenerative medicine perspective on ear reconstruction studies, addressing the advantages and disadvantages of experimental and clinical designs, including current innovations and artificial organ designs, such as stem cell-exosome strategies. The complexity of the production process, the characterization of biomaterials, the need for standardization of in vitro and in vivo protocols, ethical concerns, and high costs necessitate controlled and comparative analyses of these high-tech products/methods before they are transferred to clinical use.

Osteoarthritis (OA) is a progressive joint disorder that predominantly affects elderly and postmenopausal individuals. Current therapies offer only transient symptom relief and are associated with significant adverse effects. Mesenchymal stem cell (MSC) therapy holds promise for OA treatment, but challenges such as poor in vivo persistence and migration away from target sites hinder its clinical application. Here, we develop a bioactive, thermosensitive hydroxypropyl chitin (HPCT) hydrogel as an injectable platform to enhance MSC-based therapy. In both papain-induced early-stage and surgically induced late-stage OA models, intra-articular injections of MSCs combined with HPCT hydrogel significantly enhance therapeutic efficacy within the osteoarthritic joint environment. This bioactive, thermosensitive hydrogel is associated with attenuation of mechanical-stress-related ferroptotic signatures in chondrocytes through the establishment of a protective biomechanical microenvironment. MSCs embedded within the hydrogel adopt a spheroidal configuration, which improves their viability, enhances their anti-inflammatory properties, and prolongs their retention at the site of injury. These combined effects promote cartilage repair, regeneration, and sustained joint homeostasis. Mechanistically, these effects are accompanied by modulation of mechanotransduction-related pathways, including reduced Piezo1 expression and restoration of GPX4-associated antioxidant capacity. Our findings highlight HPCT-based tissue engineering as a promising therapeutic strategy for addressing OA pathophysiology and improving long-term clinical outcomes.

Articular cartilage repair remains a major clinical challenge. Although microfracture (MF) is widely applied, it frequently results in fibrocartilaginous repair with limited mechanical durability and unsatisfactory long-term outcomes. The persistent inflammatory microenvironment following cartilage injury disrupts tissue homeostasis and impairs chondrogenic differentiation of bone marrow stem cells (BMSCs), representing a major impediment to regeneration. Here, an injectable, thermosensitive composite hydrogel, constructed from a dopamine-modified hyaluronic acid and Pluronic F127 network, which incorporates chlorogenic acid (CA) and ZIF-8 nanoparticles encapsulated with kartogenin (KGN), is developed to establish a cascade repair strategy. Preferential release of CA can efficiently reprogram macrophages toward a pro-regenerative M2 phenotype and improve anti-inflammatory cytokine secretion, thereby creating a pro-regeneration microenvironment. Subsequently, the sustained release of KGN further stimulates BMSCs chondrogenic differentiation within this optimized niche. Biological assays demonstrate that this synergistic mechanism enhances cartilage-specific matrix synthesis and alleviates matrix degradation under inflammatory conditions. Furthermore, this composite hydrogel, combined with MF, improves cartilage tissue regeneration in a rat model, as evidenced by smooth defect filling, well-organized extracellular matrix deposition, and reduced Matrix metalloproteinase 13-mediated degradation. This work presents a synergistic immuno-chondroregenerative platform that overcomes fundamental limitations of MF and offers a promising paradigm for functional cartilage regeneration.

Osteoarthritis (OA) is a degenerative joint disease characterized by chronic inflammation and cartilage loss. However, disease-modifying treatments are still unavailable, and even promising nanomaterials are hindered by rapid clearance and poor targeting. Herein, we reported a peptide-modified and reactive oxygen species (ROS) responsive collagen hydrogel (CSH-AuNCs-CIITP) that coupled environmental adaptability with molecular precision for spatiotemporally regulated cartilage regeneration. Gold nanoclusters were functionalized with a type II collagen-targeting peptide (CIITP) for cartilage affinity and encapsulated within a ROS-cleavable disulfide-crosslinked collagen hydrogel (CSH), yielding an injectable, self-healing system with enhanced mechanical integrity and enzymatic stability. The hydrogel achieves ROS-triggered, on-demand release of therapeutic nanoclusters within the OA microenvironment. In vitro, this hydrogel system promoted BMSCs chondrogenesis and macrophage M2 polarization. In vivo, it facilitated preliminary integration and repair with robust matrix restoration. This ROS-activated cartilage-targeting platform integrates nano-bio interactions, dynamic covalent chemistry, and microenvironmental modulation. It achieves precise cartilage targeting, prolonged intra-articular retention, and spatiotemporally regulated bioactivity, culminating in superior anti-inflammatory and chondroregenerative outcomes, offering a promising strategy for nanomaterial-enabled osteoarthritis therapy.

Different tissues exhibit distinct mechanical properties, including stiffness and viscoelasticity. Both static and dynamic mechanical cues modulate cellular behaviour and induce phenotypic changes. To leverage this regulatory mechanism, researchers have engineered dynamic hydrogels through physical interactions and dynamic covalent bonds (DCBs). Prior studies demonstrate that viscoelastic hydrogels effectively direct mesenchymal stem cell (MSC) behaviour, making them promising candidates for bone tissue engineering (BTE). This review systematically summarizes (i) dynamic hydrogel crosslinking strategies (ionic, hydrogen bonding, hydrazone, boronate ester, and imine), (ii) quantitative viscoelastic modulation methods (molecular weight, crosslinking chemistry, and network architecture), and (iii) mechanotransduction pathways governing MSC proliferation, spreading, migration, osteogenesis, and chondrogenesis. Several conclusions emerge from the above perspectives: viscoelastic effects are context-dependent, varying with the cell source, dimensionality, and matrix chemistry; YAP/TAZ serves as a convergent node integrating diverse mechanosensory inputs (integrin-FAK, TRPV4, and Piezo1) into lineage-specific programs; and clinical translation faces persistent challenges from non-standardized characterization protocols, limited long-term in vivo validation, and scalable manufacturing constraints. By integrating these perspectives, this review aims to develop the rational design of ECM-mimetic dynamic hydrogels for bone and cartilage regeneration.

Osteoarthritis pain is a common chronic pain. Low intensity pulsed ultrasound (LIPUS) is a non-invasive treatment commonly used for musculoskeletal system diseases, but it is unclear whether it can alleviate osteoarthritis (OA) pain. The aim of this study is to investigate the therapeutic effects of LIPUS on pain relief and joint repair in OA rat models, and to explore its potential mechanisms. Twenty-four Sprague-Dawley rats were divided into Sham, monosodium iodoacetate (MIA), MIA + LIPUS, and MIA + Sham LIPUS groups. OA was induced via intra-articular MIA injection. LIPUS was administered for 20 minutes/14 days. Behavioral tests, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), histopathological, and immunohistochemical assessments were conducted. LIPUS significantly increased paw withdrawal thresholds (PWT) and thermal withdrawal latencies (PWL), improved gait symmetry, and enhanced total walking distance. Piezo1, Piezo2, Trpv1, and Calca (encoding CGRP) mRNA levels in dorsal root ganglia were downregulated. Histopathological and immunohistochemical analysis revealed that LIPUS treatment preserved cartilage matrix integrity, reduced cartilage surface erosion, decreased Mankin scores, and promoted cartilage regeneration. LIPUS significantly alleviated OA-induced pain and joint damage in rats by downregulating mRNA expression of pain-related molecules and promoting cartilage preservation. These findings suggested that LIPUS has the potential to be a non-invasive, non-pharmacological therapy for OA, offering a promising alternative to conventional treatments.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease with limited therapeutic options. Stem cell-based tissue engineering, particularly utilizing human periodontal ligament stem cells (hPDLSCs), represents a promising approach for cartilage regeneration. However, we have previously demonstrated that chronic inflammation and hypoxic stress in the TMJOA microenvironment markedly accelerate cellular senescence in hPDLSCs, severely impairing their regenerative potential. Here, we identify the YTHDC1–m⁶A–GADD45B axis as a critical regulator of senescence and chondrogenic differentiation in hPDLSCs. We show that YTHDC1, an m⁶A reader protein, is downregulated under inflammatory and senescent conditions. Functional studies reveal that YTHDC1 overexpression attenuates senescence and enhances chondrogenesis, whereas its knockdown exacerbates senescence and suppresses differentiation. Mechanistically, YTHDC1 recognizes m⁶A modifications on GADD45B mRNA and promotes its decay, leading to inhibition of the p53/p21 signaling pathway. Mutation of the m⁶A site in GADD45B abolishes the regulatory effects of YTHDC1. In rats with TMJOA, transplantation of YTHDC1–overexpressing hPDLSCs ameliorated disease phenotypes, an effect reversed by co-expression of wild-type GADD45B. Our findings reveal a novel epitranscriptomic mechanism that regulates hPDLSCs senescence and subsequently affects chondrogenic differentiation, and highlight the therapeutic potential of targeting the YTHDC1-GADD45B-p53/p21 axis.