Promoting implant osseointegration via the osteoblast-selective beta-amino acid polymer strategy

Osseointegration for implants, especially bioinert implants, poses significant clinical challenges. Overcoming fibrotic encapsulation and promoting osseointegration at the implant interface are critical for successful bone regeneration, which highly expected biomaterials with osteoblast over fibroblast selectivity. However, few materials possess the function. Beta-amino acid polymers have demonstrated cell adhesion property, easy preparation, and superior stability to resist proteolysis as emerging biomaterials. Here, we developed amphiphilic beta-amino acid polymers that demonstrate exceptional osteoblast vs fibroblast selectivity, outperforming the natural osteoblast-selective KRSR peptide. The optimal polymer selectively supports osteoblast adhesion by manipulating the adsorption of serum proteins and the presentation of RGD motifs on polymer-modified surfaces. In vivo study using polymer-modified titanium-implants in rat maxillary bone revealed that the optimal polymer substantially promotes osseointegration of titanium-implants compared to uncoated titanium-implants, which tend to develop fibrous encapsulation. This study demonstrates the effectiveness of our strategy in designing osteoblast-selective biomaterials and implies the promising application of beta-amino acid polymer as emerging osteoblast-selective biomaterials to promote osseointegration.