Development of Biomimetic and Bioactive 3D Nanocomposite Scaffolds for Osteochondral Regeneration

Abstract

Osteochondral tissue is composed of ordered and random biological nanostructures and can, in principal, be classified as a nanocomposite material. Thus, the objective of this research is to develop a novel biomimetic biphasic nanocomposite scaffold via a series of 3D fabricating techniques for osteochondral tissue regeneration. For this purpose, a highly porous Poly(caprolactone) (PCL) bone layer with bone morphogenetic protein-2 (BMP-2)-encapsulated Poly(dioxanone) (PDO) nanospheres and nanocrystalline hydroxyapatite was photocrosslinked to a Poly(ethylene glycol)-diacrylate (PEG-DA) cartilage layer containing transforming growth factor-β1 (TGF-β1)-encapsulated PLGA nanospheres. Novel tissue-specific growth factor-encapsulated nanospheres were efficiently fabricated via a wet co-axial electrospraying technique. Integration and porosity of the distinct layers was achieved via co-porogen leaching and ultraviolet (UV) photocrosslinking of water soluble poly(ethylene glycol) (PEG) and <150 um sodium chloride salt particles providing greater control over pore size and increased surface area. Our in vitro results showed significantly improved human bone marrow derived mesenchymal stem cells (hMSCs) adhesion and differentiation in bone and cartilage layers, respectively. In addition, we are working on developing a novel table top stereolithography (SL) apparatus for the manufacture of custom designed 3D biomimetic scaffolds with incorporated growth factor encapsulated nanospheres for osteochondral defect repair. Our early-stage SL development has illustrated good corroboration between computer-aided design (CAD) and manufactured constructs with controlled geometry. The ultimate goal of the novel tabletop SL system is the manufacture of patient-specific implantable 3D nanocomposite scaffolds for osteochondral defect repair. The current SL system developed in our lab allows for efficient photocrosslinking of two novel nanocomposite polymeric materials for the manufacture of three-dimensional (3D) osteochondral constructs with good spatiotemporal control of growth factor release in addition to exhibiting similar mechanical properties to that of the native tissues being addressed.