Marchena Metzli Hernandez, Lambert Elisa, Bogdanović Bojana, Quadir Fauzia, Neri-Cruz Carlos E, Luo Jiajun, Nadal Clemence, Migliorini Elisa, Gautrot Julien E
School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, U.K.
University Grenoble Alpes, INSERM, CEA, CNRS, U1292 Biosanté, EMR 5000, 17 Av des Martyrs, Grenoble 38000, France.
ACS Appl Mater Interfaces. 2024 Aug 7;16(31):40455-40468. doi: 10.1021/acsami.4c05139. Epub 2024 Jul 29.
Bone morphogenetic proteins (BMPs) are important targets to incorporate in biomaterial scaffolds to orchestrate tissue repair. Glycosaminoglycans (GAGs) 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 GAG mimetic interfaces for the stable capture of BMPs. The growth of PSPMA brushes via a surface-initiated activator regenerated by electron transfer polymerization is investigated via ellipsometry, prior to characterization of swelling and surface chemistry via X-ray photoelectron spectroscopy and Fourier transform infrared. The capacity of PSPMA brushes to bind BMP2 and BMP4 is then characterized 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 a quartz crystal microbalance with dissipation monitoring, providing some insights 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 that 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 functionalized PSPMA brushes. The presence of BMP2 and the architecture of the brush are found to have a significant impact on matrix deposition at the corresponding interfaces. Therefore, PSPMA brushes emerge as attractive coatings for scaffold engineering and stable capture of BMP2 for regenerative medicine applications.
骨形态发生蛋白(BMPs)是生物材料支架中用于协调组织修复的重要靶点。糖胺聚糖(GAGs)如肝素能够捕获BMPs并将其以安全浓度保留在生物材料表面。尽管肝素对调节骨骼和组织修复的两种重要生长因子BMP2和BMP4具有很强的亲和力,但它仍难以稳定地嵌入多种生物材料表面,并且在体外和体内都会迅速降解。在本报告中,提出了仿生聚(甲基丙烯酸磺丙酯)(PSPMA)刷作为硫酸化GAG模拟界面,用于稳定捕获BMPs。在通过X射线光电子能谱和傅里叶变换红外光谱对溶胀和表面化学进行表征之前,通过椭偏仪研究了通过表面引发的电子转移聚合再生的活化剂生长PSPMA刷的情况。然后通过表面等离子体共振表征PSPMA刷结合BMP2和BMP4的能力。发现BMP2特别稳定且高密度地锚定在PSPMA刷表面,并且观察到刷结构对结合能力有强烈影响。使用具有耗散监测的石英晶体微天平进一步证实了这些结果,这为BMPs在PSPMA刷表面的吸附模式提供了一些见解。在厚而致密的刷上观察到BMP2的初级吸附,渗透相对较少,这意味着这种生长因子应该可以用于相应细胞膜受体的进一步结合。最后,为了证明PSPMA刷对BMP2捕获的影响,然后在功能化的PSPMA刷表面培养真皮成纤维细胞。发现BMP2的存在和刷的结构对相应界面处的基质沉积有显著影响。因此,PSPMA刷成为用于支架工程和再生医学应用中稳定捕获BMP2的有吸引力的涂层。