Bacteria-responsive, Cell-recruitable, and osteoinductive nanocomposite microcarriers for intelligent bacteriostasis and accelerated tissue regeneration

Abstract

Repairing alveolar bone defects with chronic periodontitis is a major clinical challenge, since the periodontitis causes the intermittent bacteria invasion to irreversibly aggravates the degeneration of alveolar bones. To deal with the challenge, a kind of novel microcarriers with excellent abilities of responding to alkaline phosphatase (ALP) to intelligently eliminate the bacteria and promoting the recruitment and osteogenic differentiation of endogenous stem cells are developed. Mesoporous silica nanocarriers that chemically fix the polyethylene glycol-modified amoxicillin (PEG-AML) through the phosphoester groups and electrostatically adsorb the aspirin (ASP) are first prepared. The nanocarriers are then dispersed in a chitosan solution to prepare the bacteria-responsive, cell-recruitable, and osteoinductive nanocomposite microcarriers. When being stimulated by ALP that are secreted by the bacteria, phosphoester groups of microcarriers are cleaved, and PEG-AML are delivered on demand to well achieve the goal of intelligent bacteriostasis. The microcarriers slowly release the ASP to promote the recruitment and osteogenic differentiation of endogenous stem cells. At 8 weeks post-implantation, the microcarriers facilitate the repair of alveolar bone defects with periodontitis. The blood vessels in the neo-generated alveolar bones grow well. Due to the appropriate degradation time and excellent antibacterial ability of microcarriers, the microcarriers exhibit a better therapeutic efficacy than the standard clinical products (Geistlich Bio-Oss®), providing a new insight into the cure of alveolar bone defects with periodontitis.