Abstract:
Background Articular cartilage exhibits limited self-repair capability after injury and is prone to progressing toward osteoarthritis. Conventional repair approaches face inherent limitations, while tissue engineering offers a novel strategy for cartilage regeneration.
Objective To construct a curcumin-loaded CSMA/Wharton's jelly composite hydrogel and systematically elucidate its physicochemical characteristics, biocompatibility, and immunomodulatory effects, as well as its capacity to enhance chondrogenesis of BMSCs in an inflammatory microenvironment.
Methods The CWC composite hydrogel was fabricated via 405 nm ultraviolet light-induced crosslinking. Its morphology and physicochemical properties were characterized by scanning electron microscopy (SEM) and swelling experiments. The biocompatibility and proliferative effects of hydrogel extracts from the three groups—CSMA, CW (CSMA/Wharton's jelly), and CWC—on rat BMSCs were evaluated using the CCK-8 assay, live/dead staining, and phalloidin staining. The immunomodulatory function of the materials was assessed by detecting the expression of M1/M2 macrophage phenotype-related markers (e.g., CD86, CD206) through quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining.Under an inflammatory microenvironment induced by interleukin 1β (IL1β), the chondrogenic differentiation capacity of BMSCs was evaluated by measuring the expression levels of key chondrogenic genes, including Sox9, Col2, Acan, and Col1, via qRT-PCR.
Results The CWC hydrogel exhibited a stable, homogeneous, and interconnected three-dimensional porous structure. Curcumin was successfully loaded, and the incorporation of Wharton's jelly resulted in a more compact network architecture. Biological evaluation indicated that all three groups of materials showed no obvious cytotoxicity and supported cell proliferation and spreading. In terms of immunomodulation, the CWC hydrogel significantly downregulated the mRNA expression of M1 macrophage markers (IL‑1β, CD86) and upregulated that of M2 markers (Arg1, CD206), effectively polarizing macrophages toward an anti‑inflammatory phenotype. Under inflammatory conditions, the CWC hydrogel markedly reversed the IL‑1β‑induced suppression of chondrogenic differentiation, enhanced the expression of cartilage‑specific genes (Sox9, Col2, Acan), and concurrently suppressed Col1 expression. Its protective and pro‑chondrogenic effects were superior to those of the CSMA and CW groups.
Conclusion A curcumin-loaded, photocrosslinked CSMA/Wharton's jelly composite hydrogel has been successfully fabricated.The material demonstrates favorable biocompatibility and significant immunomodulatory capacity, and effectively protects against inflammatory damage while promoting the chondrogenic differentiation of BMSCs. The incorporation of curcumin endows the scaffold with distinct anti-inflammatory and pro‑chondrogenic activities. Combined with the biomimetic microenvironment provided by Wharton's jelly, the system achieves a synergistic "anti‑inflammatory and pro‑regenerative" effect, offering a novel functionalized scaffold strategy for cartilage repair.
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