Cell-free and cytokine-free self-assembling peptide hydrogel-polycaprolactone composite scaffolds for segmental bone defects

Segmental bone defects over the self-healing threshold are a major challenge for orthopedics. Despite the advancements in clinical practice, traditional tissue engineering methods are limited by the addition of heterogeneous cells and cytokines, leading to carcinoma or other adverse effects. Here, we present a cell-free and cytokine-free strategy using an ECM-mimetic self-assembling peptide hydrogel (SAPH)- polycaprolactone (PCL) composite scaffold. The hydrophilic SAPH endows the rigid PCL scaffold with excellent biocompatibility and preference for osteogenesis induction. The autologous cells around the bone defect site immediately grew, proliferated, and secreted ECM and cytokines after contacting the implanted SAPH-PCL composite scaffold, and the bone repair of rabbit ulnar segmental bone defect was achieved in just six months. Quantitative proteomic analysis reveals that the SAPH-PCL composite scaffold accelerates osteoblastogenesis, osteoclastogenesis, and angiogenesis with moderate immune responses and negligible effects on pathological fibrosis. These findings have important implications for the potential clinical applications of the SAPH-PCL composite scaffold in patients with segmental bone defects and identify the mechanisms of action for accelerated segmental bone defect repair.