Forming A More Perfect Union: Fabricating Bioinstructive Scaffolds To Mimic The Osteogenic Niche For Bone Repair

Abstract

Engineered bone graft designs have been largely inspired by adult bone despite significant deviation from the composition of anabolic bone. Highly osteogenic extracellular matrix (ECM) secreted by human mesenchymal stem cells (hMSCs) derived from bone marrow or induced pluripotent stem cells was combined with inorganic bone components from natural (Mg-doped hydroxyapatite) and synthetic (nanosilicates) sources to generate next-generation bone grafts ranging from lyophilized collagen slabs to 3D-printed nanocomposite scaffolds. While direct deposition of the ECM onto scaffolds by cultured hMSCs under static conditions was effective, perfusion culture increased the volumetric distribution of ECM. To provide greater flexibility and simplification to ECM surface modification of scaffolds, metabolically-labeled ECM with azide functional groups was solubilized and covalently tethered to functionalized scaffolds via strain-promoted azide-alkyne cycloaddition (SPAAC). These studies demonstrate a range of approaches to biofabricating grafts using hMSC-derived osteogenic matrices for bone healing.