Platelet-rich plasma (PRP) is rich in growth factors and has commonly been utilized in the repair and regeneration of damaged articular cartilage. However, the major drawbacks of direct PRP injection are unstable biological fixation and fast or burst release of growth factors. Fucoidan is a heparinoid compound that can bind growth factors to control their release rate. Furthermore, fucoidan can reduce arthritis through suppressing inflammatory responses and thus it has been reported to prevent the progression of osteoarthritis, promote bone regeneration and accelerate healing of cartilage injury. Injectable hydrogels can be used to deliver cells and growth factors for an alternative, less invasive treatment of cartilage defects. In this study, hyaluronic acid (HA) and fucoidan (FD) was blended with gelatin (GLT) and the GLT/HA/FD hybrid was further cross-linked with genipin (GP) to prepare injectable GP-GLT/HA/FD hydrogels. The gelation rate was affected by the GP, GLT, HA and FD concentrations, as well as the pH values. The addition of HA and FD to GLT networks improved the mechanical strength of the hydrogels and facilitated the sustained release of PRP growth factors. The GP-GLT/HA/FD hydrogel showed adequate injectability, shape-persistent property and strong adhesive ability, and was more resistant to enzymatic degradation. The PRP-loaded GP-GLT/HA/FD hydrogel promoted cartilage regeneration in rabbits, which may lead to an advanced PRP therapy for enhancing cartilage repair.

The regenerative potential of stem cells and growth factors and their promising roles in revolutionizing osteoarthritis treatment. The image was generated using BioRender.

Proteolytic fragments of fibronectin can have catabolic effects on cartilage, menisci, and synovium. Previous studies have reported that Toll-like receptor (TLR) signaling pathways might be associated with joint inflammation and joint destruction. Platelet-rich plasma (PRP) is increasingly being used to treat a range of joint conditions; however, it has yet to be determined whether PRP influences fibronectin fragment (FN-f) procatabolic activity and TLRs. In this study, human primary culture cells were treated with 30 kDa FN-f with/without PRP co-incubation, and then analyzed using real-time PCR to determine gene expression levels in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts. Protein levels were evaluated by Western immunoblotting. This study observed an increase in the protein expression of matrix metalloproteinases (MMPs), Toll-like receptor 2 (TLR2), nitric oxide synthase 2 (NOS2), prostaglandin-endoperoxide synthase (PTGS2), and cyclooxygenase 2 (COX2) in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts following insult with 30 kDa FN-f. Upregulation of these genes was significantly attenuated by PRP treatment. TLR2 and matrix metalloproteinase 13 (MMP-13) were also significantly attenuated by cotreatment with 30 kDa FN-f + PRP + TLR2 inhibitor. PRP treatment was shown to attenuate the 30 kDa FN-f-induced MMP-13 expression associated with the decreased expression of TLR2 in osteoarthritic chondrocytes and synovial fibroblasts. PRP treatment was also shown to attenuate procatabolic activity associated with MMP-13 expression via the TLR2 signaling pathway.

Osteoarthritis (OA) remains a major clinical challenge due to the lack of effective treatments capable of halting disease progression. Chronic synovial inflammation and cartilage degradation are hallmark features, wherein galectin-3 (Gal-3), a β-galactoside-binding lectin, plays a pivotal upstream role by driving M1 macrophage activation and chondrocyte apoptosis. Modified citrus pectin (MCP), a natural Gal-3 binder, possesses therapeutic potential but is hindered by rapid clearance and limited joint retention. Herein, we present oxidized MCP (oxMCP), structurally reprogrammed MCP, that functions as a Gal-3-sequestering and crosslinkable matrix. This transformation was achieved via periodate oxidation, which introduced dialdehyde groups for Schiff base crosslinking with N, O-carboxymethyl chitosan (NOCC), while simultaneously enhancing Gal-3 affinity by reducing the molecular weight, increasing the chain flexibility, and exposing β-(1 → 4)-galactan motifs. These changes markedly amplified Gal-3-associated bioactivities, including M1 macrophage suppression and chondroprotection. The resulting oxMCP/NOCC hydrogel was further integrated with berberine (BBR), a cationic alkaloid with M2-polarizing activity, which reinforced the hydrogel network via non-covalent interactions and empowered the M2-polarizing capacity. The oxMCP/NOCC/BBR hydrogel exhibited excellent self-healing, low swelling, slow degradation, and sustained drug release, key features for intra-articular delivery. In vitro, it suppressed oxidative stress, matrix degradation, and chondrocyte apoptosis while promoting macrophage polarization toward the M2 phenotype. In vivo, intra-articular administration alleviated synovial inflammation and preserved cartilage in a rat OA model. This work transformed MCP from a short-acting Gal-3 blocker into a durable, bioactivity-enhanced therapeutic platform with immunomodulatory and cartilage-protective capabilities, offering a transformative strategy for a localized pathology-adaptive OA intervention.