Construction of a Localized and Long-Acting CCN2 Delivery System on Percutaneous Ti Implant Surfaces for Enhanced Soft-Tissue Integration.

ABSTRACT

Soft-tissue integration (STI) plays an essential role in the long-term success of percutaneous Ti implants since it acts as a biological barrier that protects the soft and hard tissue around implants. Surface modification of Ti implants with drug-release properties to achieve soft-tissue regeneration has been proven to be effective in STI. However, the short-acting effect caused by the uncontrolled drug release of the topical delivery system limits long-term STI enhancement. Herein, a long-acting protein delivery system for Ti implants that involved micro-arc oxidation of Ti surfaces (MAO-Ti) and localized immobilization of cellular communication network factor 2 (CCN2) bearing mesoporous silica nanoparticles (MSNs) on MAO-Ti was prepared, namely, CCN2@MSNs-Ti. The CCN2 release study of CCN2@MSNs-Ti demonstrated a sustained-release profile for 21 days, which was able to maintain long-term stable STI. In addition, in vitro cell behavior evaluation results indicated that CCN2@MSNs-Ti could promote the STI-related biological response of human dermal fibroblasts via the FAK-MAPK pathway. More importantly, the system could effectively enhance STI after 4 weeks and proinflammatory factors in the soft tissue decreased significantly in a rat model of implantation. These results denote that CCN2@MSNs-Ti showed an appealing application prospect for enhanced STI around transcutaneous Ti implants, which would ultimately result in an increased success rate of percutaneous Ti implants.