Chitosan/Dextran Hydrogel Constructs Containing Strontium-Doped Hydroxyapatite with Enhanced Osteogenic Potential in Rat Cranium.

Abstract

It is an effective way in bone tissue engineering to promote the mechanical and osteogenic capability of hydrogels by encapsulating mineral particles into polymer matrix. In this work, we reported novel kinds of nanocomposite scaffolds based on hydroxypropyl chitosan/aldehyde dextran hydrogel (CDH) and strontium-nanohydroxyapatite (Sr-nHA) nanoparticles. The molar ratios of Sr/(Sr + Ca) at 0% (nHA), 50% (Sr50nHA), and 100% (Sr100nHA) were fabricated and subsequently incorporated into CDH. The characterization of Sr-nHA/CDH constructs and CDH alone was studied by Fourier transform infrared analysis, X-ray powder diffraction detection, and scanning electron microscopy. The physical properties of hydrogels were further detected by swelling studies, degradation behavior, rheological measurements, mechanical testing, and ion-release behavior. Cell biocompatibility on the scaffolds was determined in vitro, and bone formation in vivo was examined by a rat calvarium defect model. The results showed that either nHA or Sr-nHA nanoparticles incorporation into CDH would significantly improve the rheological and mechanical properties (P < 0.05). The Sr2+ released from the Sr100nHA/CDH was in the range of optimal concentration for pro-osteogenesis. The addition of Sr-nHA significantly enhanced the cell proliferation and osteogenic differentiation of osteoblasts (P < 0.05). The Sr100nHA/CDH exerted the highest promotion on the polarization of macrophages toward the M2 phenotype. The new bone formation of Sr100nHA/CDH was 2.5-fold and 2-fold higher than that of CDH at 4 and 8 weeks, respectively (P < 0.05). HE staining, Masson's trichrome staining, and immunofluorescence staining of OCN results also confirmed that Sr100nHA/CDH had superior bone regeneration compared to other hydrogels in vivo. In conclusion, this novel in situ gelling hydrogel based on injectable and load-bearing 100% Sr-substituted nHA in CDH is expected to have wide orthopedic, dental, and craniofacial applications to enhance bone regeneration.