Department of Materials Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States.
Department of Bioengineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States.
Bioconjug Chem. 2021 May 19;32(5):861-878. doi: 10.1021/acs.bioconjchem.1c00090. Epub 2021 Apr 15.
Growth factors play a critical role in tissue repair and regeneration. However, their clinical success is limited by their low stability, short half-life, and rapid diffusion from the delivery site. Supraphysiological growth factor concentrations are often required to demonstrate efficacy but can lead to adverse reactions, such as inflammatory complications and increased cancer risk. These issues have motivated the development of delivery systems that enable sustained release and controlled presentation of growth factors. This review specifically focuses on bioconjugation strategies to enhance growth factor activity for bone, cartilage, and osteochondral applications. We describe approaches to localize growth factors using noncovalent and covalent methods, bind growth factors via peptides, and mimic growth factor function with mimetic peptide sequences. We also discuss emerging and future directions to control spatiotemporal growth factor delivery to improve functional tissue repair and regeneration.
生长因子在组织修复和再生中起着关键作用。然而,其临床应用受到其低稳定性、半衰期短和从给药部位快速扩散的限制。通常需要超生理浓度的生长因子来证明疗效,但这可能导致不良反应,如炎症并发症和增加癌症风险。这些问题促使人们开发了能够持续释放和控制生长因子呈现的输送系统。本综述特别关注用于骨、软骨和骨软骨应用的生物共轭策略,以增强生长因子的活性。我们描述了使用非共价和共价方法定位生长因子的方法,通过肽结合生长因子,并使用模拟肽序列模拟生长因子的功能。我们还讨论了控制时空生长因子传递的新兴和未来方向,以改善功能性组织修复和再生。