Bioinspired mineral hydrogels as nanocomposite scaffolds for the promotion of osteogenic marker expression and the induction of bone regeneration in osteoporosis

Osteoporosis is one of the most prevalent age-related diseases worldwide and is characterized by a systemic deterioration of bone strength (bone mineral density and bone quality) with a resulting increase in fragility fractures. Due to the complex osteoporotic pathological environment, it is a huge challenge to induce bone regeneration under osteoporosis conditions. In this study, we successfully nanoengineer a bioinspired mineralized hydrogel from the supramolecular assembly of nano-hydroxyapatite, sodium carbonate, and polyacrylic acid, termed as CHAp-PAA. The resultant nanocomposite hydrogels can maintain their initial morphology and mechanical properties under physiological conditions, while exhibiting good primary stability, biocompatibility, bioactivity, and osteoconductivity. We demonstrate that this optimized hydrogel scaffold has shown superior performance for bone marrow stem cells (BMSCs) proliferation, differentiation, and extracellular matrix production in vitro. Remarkably, the mineralized CHAp-PAA hydrogels could be used as scaffolds for the critical-sized bone defect (6.0 mm diameter and 10.0 mm depth) in the osteoporotic rabbit model. Without the delivery of additional therapeutic agents or stem cells, these CHAp-PAA hydrogel scaffolds can improve bone ingrowth and accelerate new bone formation even in complex osteoporotic pathological environments. Therefore, this work presents a type of bioinspired multifunctional mineral hydrogel that offers an alternative strategy to manage osteoporosis. Statement of Significance We successfully nanoengineer a bioinspired mineralized hydrogel from supramolecular assembly of nano-hydroxyapatite, sodium carbonate, and polyacrylic acid, termed as CHAp-PAA. The resultant nanocomposite hydrogels can maintain their initial morphology and mechanical properties under physiological conditions, while exhibiting good primary stability, biocompatibility, bioactivity, and osteoconductivity. We demonstrate that this optimized hydrogel scaffold has shown superior performance for bone marrow stem cells (BMSCs) proliferation, differentiation, and extracellular matrix production in vitro. Remarkably, the mineralized CHAp-PAA hydrogels could be used as scaffold for the critical-sized bone defect (6.0 mm diameter and 10.0 mm depth) in osteoporotic rabbit model. Without delivery of additional therapeutic agents or stem cells, these CHAp-PAA hydrogel scaffolds can improve bone ingrowth and accelerate new bone formation even in complex osteoporotic pathological environment. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.