3D Niche-Inspired Scaffolds as A Stem Cell Delivery System for The Regeneration of The Osteochondral Interface.

The regeneration of the osteochondral unit represents a challenge due to the distinct cartilage and bonny phases present within. Current strategies focus on the development of multi-phasic scaffolds that recapitulate features of this complex unit and promote the differentiation of implanted bone-marrow derived stem cells (BMSCs). In doing so, challenges remain from the loss of stemness during in vitro expansion of the cells and the low control over the stem cell activity at the interface with scaffolds in vitro and in vivo. Here, we developed scaffolds inspired by the bone marrow niche that can recapitulate the natural healing process after injury. The construct comprises an internal depot of quiescent BMSCs, mimicking the bone marrow cavity, and an electrospun capsule that "activates" the cells to migrate into an outer "differentiation-inducing" 3D printed unit functionalized with TGF-β and BMP-2 peptides. In vitro, niche-inspired scaffolds retained a depot of non-proliferative cells capable of migrating and proliferating through the electrospun capsule. Invasion of the 3D printed cavity resulted in location-specific cell differentiation, mineralization, secretion of ALP and GAGs, and genetic upregulation of collagen II and collagen I. In vivo, niche-inspired scaffolds were biocompatible, promoted tissue formation in rat subcutaneous models, and regeneration of the osteochondral unit in rabbit defect models. This article is protected by copyright. All rights reserved.