Cell-Free Biomimetic Scaffold with Cartilage Extracellular Matrix-Like Architectures for In Situ Inductive Regeneration of Osteochondral Defects

The development of a biomimetic scaffold designed to provide a native extracellular matrix (ECM)-like microenvironment is a potential strategy for cartilage repair. The ECM in native articular cartilage is structurally composed of three different architectural zones, i.e., horizontally aligned, randomly arranged, and vertically aligned collagen fibers. However, the effects of scaffolds with these three different ECM-like architectures on in vivo cartilage regeneration are not clear. In this study, we aim to systematically investigate and compare their in situ inductive regenerative efficacy on cartilage defects. ECM-mimetic silk fibroin scaffolds with horizontally aligned, vertically aligned, and random pore architectures are fabricated using the controlled directional freezing technique. All of these scaffolds exhibit similar pore area, swelling ratio, and in vitro degradation behavior. Nevertheless, the aligned scaffolds have a higher pore aspect ratio and hydrophilicity, and increase the proliferation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. When implanted into rabbit osteochondral defects, the scaffold with vertically aligned pore architectures provides a more cell-favorable microenvironment conducive to endogenous BMSCs than other scaffolds and supports the simultaneous regeneration of cartilage and subchondral bone. These findings indicate that scaffolds with vertically aligned ECM-like architectures serve as an effective cell-free and growth factor-free scaffold for enhanced endogenous osteochondral regeneration.