Liang He, Russell Stephen J, Wood David J, Tronci Giuseppe
Clothworkers' Centre for Textile Materials Innovation for Healthcare, School of Design, University of Leeds, Leeds, United Kingdom.
Biomaterials and Tissue Engineering Research Group, School of Dentistry, St. James's University Hospital, University of Leeds, Leeds, United Kingdom.
Front Chem. 2018 Dec 17;6:626. doi: 10.3389/fchem.2018.00626. eCollection 2018.
The covalent functionalization of type I atelocollagen with either 4-vinylbenzyl or methacrylamide residues is presented as a simple synthetic strategy to achieve customizable, cell-friendly UV-cured hydrogel networks with widespread clinical applicability. Molecular parameters, i.e., the type of monomer, degree of atelocollagen functionalization and UV-curing solution, have been systematically varied and their effect on gelation kinetics, swelling behavior, elastic properties, and enzymatic degradability investigated. UV-cured hydrogel networks deriving from atelocollagen precursors functionalized with equivalent molar content of 4-vinylbenzyl ( = 18 ± 1 mol.%) and methacrylamide ( = 19 ± 2 mol.%) adducts proved to display remarkably-different swelling ratio ( = 1963 ± 58-5202 ± 401 wt.%), storage modulus (' = 17 ± 3-390 ± 99 Pa) and collagenase resistance (μ = 18 ± 5-56 ± 5 wt.%), similarly to the case of UV-cured hydrogel networks obtained with the same type of methacrylamide adduct, but varied degree of functionalization ( = 19 ± 2 - 88 ± 1 mol.%). UV-induced network formation of 4VBC-functionalized atelocollagen molecules yielded hydrogels with increased stiffness and enzymatic stability, attributed to the molecular rigidity of resulting aromatized crosslinking segment, whilst no toxic response was observed with osteosarcoma G292 cells. Although to a lesser extent, the pH of the UV-curing solution also proved to affect macroscopic hydrogel properties, likely due to the altered organization of atelocollagen molecules during network formation. By leveraging the knowledge gained with classic synthetic networks, this study highlights how the type of monomer can be conveniently exploited to realize customizable atelocollagen hydrogels for personalized medicine, whereby the structure-property relationships can be controlled to meet the requirements of unmet clinical applications.
本文介绍了一种简单的合成策略，即通过将I型去端肽胶原蛋白与4-乙烯基苄基或甲基丙烯酰胺残基进行共价功能化，以实现具有广泛临床适用性、可定制且对细胞友好的紫外光固化水凝胶网络。系统地改变了分子参数，即单体类型、去端肽胶原蛋白功能化程度和紫外光固化溶液，并研究了它们对凝胶化动力学、溶胀行为、弹性性能和酶降解性的影响。由用等摩尔含量的4-乙烯基苄基（= 18 ± 1 mol.%）和甲基丙烯酰胺（= 19 ± 2 mol.%）加合物功能化的去端肽胶原蛋白前体得到的紫外光固化水凝胶网络，其溶胀率（= 1963 ± 58 - 5202 ± 401 wt.%）、储能模量（' = 17 ± 3 - 390 ± 99 Pa）和抗胶原酶能力（μ = 18 ± 5 - 56 ± 5 wt.%）显示出显著差异，这与用相同类型甲基丙烯酰胺加合物但功能化程度不同（= 19 ± 2 - 88 ± 1 mol.%）得到的紫外光固化水凝胶网络情况类似。4VBC功能化的去端肽胶原蛋白分子的紫外诱导网络形成产生了具有更高刚度和酶稳定性的水凝胶，这归因于所得芳构化交联段的分子刚性，同时未观察到骨肉瘤G292细胞有毒性反应。尽管程度较小，但紫外光固化溶液的pH值也被证明会影响宏观水凝胶性能，这可能是由于网络形成过程中去端肽胶原蛋白分子的组织改变所致。通过利用从经典合成网络中获得的知识，本研究强调了如何方便地利用单体类型来实现用于个性化医疗的可定制去端肽胶原蛋白水凝胶，从而可以控制结构-性能关系以满足未满足的临床应用需求。
