# Facile construction of mechanically robust and highly osteogenic materials for bone regeneration

## TL;DR

This study introduces a new method to create strong, bone-generating hydrogels that could improve load-bearing bone repair.

## Contribution

A novel mineralization approach to fabricate hydrogels with mechanical strength and osteogenic properties surpassing natural bone.

## Key findings

- Mineralized hydrogels achieved compressive strength and modulus exceeding trabecular bone.
- In vivo tests showed enhanced angiogenesis and accelerated fracture healing.
- Transcriptome analysis revealed regulation of extracellular matrix and biomineralization.

## Abstract

Hydrogel-based materials exhibit great potential in tissue engineering. However, their mechanical weakness limits applications in hard tissue regeneration, especially under load-bearing conditions. Although various strengthening strategies have been applied, the achieved mechanical response of hydrogels still lags behind the mechanics of natural bone. In this study, we present a novel mineralization approach to fabricate mechanically robust and highly osteogenic mineralized hydrogels. Cross-linking between deprotonated chains of poly(acrylic acid) (PAA) and divalent cations has led to formation of hydrogels with a compressive strength and elastic modulus of 0.3 ± 0.1 kPa and 1.3 ± 0.2 kPa, respectively. Subsequent in situ formation of nano-calcium hydroxide crystals remarkably increased the compressive strength and modulus to 7.9 ± 0.6 MPa and 339.3 ± 31.4 MPa, respectively, surpassing those of trabecular bone. Moreover, the mineralized hydrogels demonstrated remarkable osteogenic potential in vivo, exhibiting immunoregulatory activity, promoting early angiogenesis, and accelerating fracture healing at weeks 4 and 8. The mechanism of osteogenesis was further revealed by transcriptome sequencing, indicating that the mineralized hydrogels regulated the translation of extracellular matrix and biomineralization. Overall, our study presents a pioneering and cost-effective method for fabricating materials with exceptional mechanical strength and strong osteogenic properties, offering a promising avenue for load-bearing bone repair applications of hydrogel-based materials.

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