A highly interweaved HA-SS-nHAp/collagen hybrid fibering hydrogel enhances osteoinductivity and mineralization

Abstract

The combination of bioactive hydroxyapatite (HAp) with biomimetic bone matrix biomaterials as bone filling scaffolds is a promising strategy for bone regeneration, but the undesirable dispersion of HAp and its interfacial interaction result in inefficient mineralization, mechanical instability, incomplete osteointegration, and even repair failure. Herein, the size dispersion and stabilization of nano-hydroxyapatite (nHAp) in aqueous media were obviously improved by hydrophilic solubilisation and strong negatively charged thiolated hyaluronic acid (HA-SH). Furthermore, the highly interweaved HA-SS-nHAp/collagen hybrid fibering hydrogel exhibited significantly improved mechanical properties and structural stability due to its thickened and densified interweaved fiber network, which ensured the homogeneous dispersion of nHAp in the matrix materials and its integration with the hydrogel network structure completely by covalent self-crosslinking among the sulfhydryl groups derived from the free HA-SH polymer and the mercapto functional groups on the surface of nHAp. Compared with the physically combined micro-hydroxyapatite (μHAp) (d ≤25 μm) and nHAp (∼530 nm) with injectable bionic HA-SH and collagen type I biopolymers, HA-SS-nHAp/collagen achieved the maximum efficiency in facilitating rabbit bone marrow stromal cell (rBMSC) adhesion, proliferation and osteogenic differentiation in vitro. The in vivo murine dorsal subcutaneous implantation results further confirmed that the interweaved fiber network structure in HA-SS-nHAp/collagen significantly promoted osteoinductivity and mineralization. This work provides novel insights for the development of new low invasive bone filling biomaterials.