Accelerating bone regeneration in cranial defects using an injectable organic–inorganic composite hydrogel

Abstract

Bone tissue engineering, as an important and attractive multidisciplinary field, affords a feasible strategy for large bone defects which are difficult to heal without clinical intervention. However, the complicated requirements of bone regeneration result in the imperfect performance of many current materials. Inspired by the composite nature of bone tissues, we proposed an organic–inorganic composite strategy. Specifically, we loaded a bone regeneration drug (simvastatin, SIM) and an inorganic component (strontium hydrogen phosphate (SrHPO₄)/beta-tricalcium phosphate (β-TCP)) to a thermogel, constituted by poly(ε-caprolactone-co-D,L-lactide)–poly(ethylene glycol)–poly(ε-caprolactone-co-D,L-lactide) (PCLA–PEG–PCLA), with a thermo-induced sol–gel transition, to prepare an injectable composite for bone regeneration in cranial defects. The SIM/(Sr/β-TCP)/PCLA–PEG–PCLA composite was able to be conveniently injected and it spontaneously filled the defect. The appropriate mechanical strength obtained by thermogelation under the stimuli of the body temperature provided the necessary support while the capacity of loading drugs and bioceramics offered bioactivity and osteoinduction. In vitro drug release experiments demonstrated a gentle and sustained release of SIM for as long as 2 months, benefitting bone regeneration. The excellent capacity of promoting the formation of osteocytes was proved by cell differentiation assays. Furthermore, the enhanced bone regeneration capacity was verified by the micro-CT results of rat cranial defects with implantation time. Based on our results, the organic–inorganic composite integrates the advantages of each component and is far beyond, thus it might serve as a promising material candidate for bone regeneration.