Endowing bone regeneration materials with both stem cell
recruitment
and osteoinduction properties is a key factor in promoting osseointegration
of titanium (Ti) implants. In this study, Apt19s-grafted oxidized
hyaluronic acid (OHA) was deposited onto a protein-mediated biomineralization
hydroxyapatite (HAp) coating of Ti. HAp was achieved by the treatment
of lysozyme and tris(2-carboxyethyl) phosphonate mixture and then
soaked in calcium ion (Ca2+) solution to obtain functional
Ti substrate (Ti/HAp/OHA-Apt). In vitro studies confirmed
that Ti/HAp/OHA-Apt could effectively maintain the sustained release
of Apt19s from Ti for 7 days. The released Apt19s significantly enhanced
the migration of bone marrow mesenchymal stem cells (MSCs), which
was reflected by the experiment of transwell assay, wound healing,
and zymogram detection. Compared with pure Ti, Ti/HAp/OHA-Apt was
able to adjust the adsorption of functional proteins at the Ti-based
interface to expose their active sites, which significantly increased
the expression of adhesion-associated proteins (vinculin and tensin)
in MSCs to promote their adhesion on Ti-based interface. In
vitro cell experiments of alkaline phosphatase activity staining,
mineralization detection, and expression of osteogenesis-related genes
showed that Ti/HAp/OHA-Apt significantly enhanced the osteogenic differentiation
ability of MSCs, which may be highly related to the porous structure
of hydroxyapatite on Ti interface. In vivo test of
Micro-CT, H&E staining, and histochemical staining further confirmed
that Ti/HAp/OHA-Apt was able to promote MSC recruitment at the peri-implant
interface to form new bone. This work provides a new approach to develop
functional Ti-based materials for bone defect repair.