Mussel-inspired tough and stiff injectable gels from inter-linked microgels

恢复受损组织的机械性能的注射凝胶可以为慢性疼痛提供微创解决方案，而无需手术。尽管它们具有潜力，但可注射凝胶尚未达到其非可注射凝胶表亲的高机械性能。腕关节损伤是全球残疾的主要原因，2020年美国的经济负担估计为2000亿美元。每年有160万患者接受外科手术来修复肌腱、韧带和软骨。在之前EPSRC资助的研究中，我们发现了一种在生理条件下将亚微观海绵状聚合物颗粒（微凝胶，MG）相互连接以形成称为双交联微凝胶（DXMG）的可注射凝胶的方法。这些DXMG成功地增强了压缩椎间盘的机械性能，并被带到诊所。在这项研究中，我们的目标是建立一个新的类注射DXMG设计用于修复承重组织的经验紧张。这些新型DXMG的韧性（抗撕裂性）和刚度（模量）值与不可注射的高性能合成凝胶和软骨相匹配。我们的新型DXMG将结合联合收割机和紧密可逆（动态）网络。用于后者的化学基团的灵感来自贻贝holdfasts。本研究旨在研究设计坚韧和坚硬的可注射DXMG的原则，并获得概念验证数据，以使其未来能够用于软骨，肌腱，肌肉和韧带修复。

Injectable gels that restore the mechanical properties of damaged tissue can provide minimally-invasive solutions to chronic pain without surgery. Despite their potential, injectable gels have not reached the high mechanical performance of their non-injectable gel cousins. Cartilage injury is a major cause of disability worldwide with an economic burden in the US estimated as US$200B in 2020. Annually, 1.6 M patients undergo surgical procedures to repair tendons, ligaments and cartilage. In previous EPSRC-funded research we discovered a method for inter-linking sub-microscopic sponge-like polymer particles (microgels, MGs) under physiological conditions to form injectable gels termed doubly crosslinked microgels (DXMGs). Those DXMGs successfully augmented the mechanical properties of compressed intervertebral discs and are being taken to the clinic. In this study we aim to establish a new class of injectable DXMGs designed for the repair of load-bearing tissues that experience tension. These new DXMGs are designed to have toughness (tearing resistance) and stiffness (modulus) values that match those of non-injectable high-performance synthetic gels and also cartilage. Our new DXMGs will combine a loose permanently bonded network with a tight reversible (dynamic) network. The chemical groups used for the latter are inspired by mussel holdfasts. This study aims to investigate the principles underpinning the design of tough and stiff injectable DXMGs and also to obtain proof-of-concept data to enable their future development for cartilage, tendon, muscle and ligament repair.