BMP-Binding Polysulfonate Brushes to Control Growth Factor Presentation and Regulate Matrix Remodelling

29 March 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Bone morphogenetic proteins (BMPs) are important targets to incorporate in biomaterials scaffolds to orchestrate tissue repair. Glycosaminoglycans such as heparin allow the capture of BMPs and their retention at the surface of biomaterials, at safe concentrations. Although heparin has strong affinities for BMP2 and BMP4, two important types of growth factors regulating bone and tissue repair, it remains difficult to embed stably at the surface of a broad range of biomaterials and degrades rapidly in vitro and in vivo. In this report, biomimetic poly(sulfopropyl methacrylate) (PSPMA) brushes are proposed as sulfated glycosaminoglycan mimetic interfaces for the stable capture of BMPs. The growth of PSPMA brushes via surface-initiated activator regenerated by electron transfer (SI-ARGET) polymerisation is investigated via ellipsometry, prior to characterisation of swelling and surface chemistry via X-ray photoelectron spectroscopy and FTIR. The capacity of PSPMA brushes to bind BMP2 and BMP4 is then characterised via surface plasmon resonance. BMP2 is found to anchor particularly stably and at high density at the surface of PSPMA brushes and a strong impact of the brush architecture on binding capacity is observed. These results are further confirmed using quartz crystal microbalance with dissipation monitoring, providing some insight into the mode of adsorption of BMPs at the surface of PSPMA brushes. Primary adsorption of BMP2, with relatively little infiltration is observed on thick dense brushes, implying this growth factor should be accessible for further binding of corresponding cell membrane receptors. Finally, to demonstrate the impact of PSPMA brushes for BMP2 capture, dermal fibroblasts were then cultured at the surface of functionalised PSPMA brushes. The presence of BMP2 and the architecture of the brush are found to have a significant impact on matrix deposition at corresponding interfaces. Therefore, PSPMA brushes emerge as attractive coatings for scaffold engineering and the stable capture of BMP2 for regenerative medicine applications.

Keywords

BMP2
polymer brush
ATRP
biomimetic
sulfonate

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