Work

Composite hydrogel modulates regulatory T cell-mediated osteoimmunomodulatory osteogenesis for steroid-induced osteonecrosis of the femoral head

Year: 2025

Type: article

Abstract: Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent condition in clinical settings, often leading to femoral head collapse without timely intervention, necessitating total hip arthroplasty (THA). However, THA carries significant financial costs and substantial risks, such as periprosthetic infection, aseptic loosening, and the need for revision surgery. Drilling and decompression combined with autologous bone grafting are widely utilized to treat early-stage SONFH. Nevertheless, the drawbacks of autologous bone graft harvesting limit its clinical utility. Many studies have sought to replace autologous grafts with biomaterials to mitigate these adverse effects. However, the role of regulatory T cells (Tregs) in the osteonecrotic region is often ignored. The reduced quantity and impaired function of Tregs in the osteonecrotic region hinder the Treg-mediated osteogenic differentiation of BMSCs and M2 polarization of macrophages, disrupting the immune microenvironment and stalling bone repair. We prepared an injectable functionalized hydrogel (MSIL-2/nHA@GelCCL22), capable of releasing CCL22 and IL-2 to recruit Tregs, and activate them via the JAK3/STAT5/Foxp3 pathway. This intervention promoted macrophage M2 polarization, osteogenic differentiation of BMSCs, and vascularization of HUVECs. In a rabbit SONFH model, implantation of MSIL-2/nHA@GelCCL22 successfully mobilized Treg homing, stimulated osteogenesis and angiogenesis, and facilitated femoral head repair. In summary, MSIL-2/nHA@GelCCL22 effectively recruits and activates Tregs, enhancing osteoimmunomodulatory processes to repair SONFH.

Source: Materials & Design

DOI: 10.1016/j.matdes.2025.115186