Lopez-Silva Tania L, Cristobal Carlo D, Edwin Lai Cheuk Sun, Leyva-Aranda Viridiana, Lee Hyun Kyoung, Hartgerink Jeffrey D
Department of Chemistry and Bioengineering, Rice University, Houston, TX, 77005, USA.
Integrative Program in Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX, 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, 77030, USA.
Biomaterials. 2021 Jan;265:120401. doi: 10.1016/j.biomaterials.2020.120401. Epub 2020 Sep 19.
Multidomain peptide (MDP) hydrogels are a class of self-assembling materials that have been shown to elicit beneficial responses for soft tissue regeneration. However, their capacity to promote nervous system regeneration remains unknown. The peripheral nervous system (PNS) substantially recovers after injury, partly due to the abundance of extracellular matrix (ECM) components in its basal lamina. However, severe peripheral nerve injuries that significantly damage the ECM continue to be a major clinical challenge as they occur at a high rate and can be extremely detrimental to patients' quality of life. In this study, a panel of eight MDPs were designed to contain various motifs mimicking extracellular matrix components and growth factors and successfully self-assembled into injectable, nanofibrous hydrogels. Using an in vitro screening system, various lysine based MDPs were found to enhance neurite outgrowth. To test their capacity to promote nerve regeneration in vivo, rat sciatic nerve crush injury was performed with MDP hydrogels injected directly into the injury sites. MDP hydrogels were found to enhance macrophage recruitment to the injury site and degrade efficiently over time. Rats that were injected with the MDP hydrogel K and laminin motif-containing MDPs K-IIKDI and K-IKVAV were found to have significantly accelerated functional recovery and remyelination compared to those injected with HBSS or other MDPs. These results demonstrate that MDPs enhance neurite outgrowth and promote a multicellular pro-regenerative response in peripheral nerve injury. This study provides important insights into the potential of MDPs as biomaterials for nerve regeneration and other clinical applications.
多结构域肽（MDP）水凝胶是一类自组装材料，已被证明能引发对软组织再生有益的反应。然而，它们促进神经系统再生的能力仍不清楚。外周神经系统（PNS）在损伤后能显著恢复，部分原因是其基膜中细胞外基质（ECM）成分丰富。然而，严重损伤ECM的外周神经损伤仍然是一个重大临床挑战，因为其发生率高，且对患者生活质量极为不利。在本研究中，设计了一组包含模拟细胞外基质成分和生长因子的各种基序的8种MDP，并成功自组装成可注射的纳米纤维水凝胶。使用体外筛选系统，发现各种基于赖氨酸的MDP可增强神经突生长。为了测试它们在体内促进神经再生的能力，对大鼠坐骨神经进行挤压损伤，并将MDP水凝胶直接注射到损伤部位。发现MDP水凝胶可增强巨噬细胞向损伤部位的募集，并随时间有效降解。与注射HBSS或其他MDP的大鼠相比，注射MDP水凝胶K以及含层粘连蛋白基序的MDPs K-IIKDI和K-IKVAV的大鼠功能恢复和髓鞘再生明显加快。这些结果表明，MDP可增强神经突生长，并在外周神经损伤中促进多细胞促再生反应。本研究为MDP作为神经再生和其他临床应用生物材料的潜力提供了重要见解。
