Polymer Program, Institute of Materials Science, University of Connecticut, 97 North Eagleville Road Unit 3136, Storrs, CT 06269-3136, USA.
Department of Chemistry, University of Connecticut, 55 North Eagleville Road Unit 3060, Storrs, CT 06269-3060, USA.
J Mater Chem B. 2020 Dec 7;8(45):10392-10406. doi: 10.1039/d0tb01990a. Epub 2020 Oct 28.
Bombyx mori silk fibroin is a fibrous protein whose tunable properties and biocompatibility have resulted in its utility in a wide-variety of applications, including as drug delivery vehicles, wound dressings, and tissue engineering scaffolds. Control of protein and cell attachment is vital to the performance of biomaterials, but silk fibroin is mostly hydrophobic and interacts nonspecifically with cells and proteins. Silk functionalised with hydrophilic polymers reduces attachment, but the low number of reactive sites makes achieving a uniform conjugation a persistent challenge. This work presents a new approach to grow brush-like polymers from the surface of degradable silk films, where the films were enriched with hydroxyl groups, functionalised with an initiator, and finally reacted with acrylate monomers using atom transfer radical polymerisation. Two different routes to hydroxyl enrichment were investigated, one involving reaction with ethylene oxide (EO) and the other using a two-step photo-catalysed oxidation reaction. Both routes increased surface hydrophilicity, and hydrophilic monomers containing either uncharged (poly(ethylene glycol), PEG) pendant groups or zwitterionic pendant groups were polymerised from the surfaces. The initial processing of the films to induce beta sheet structures was found to impact the success of the polymerizations. Compared to the EO modified or unmodified silk surfaces, the oxidation reaction resulted in more polymer conjugation and the surfaces appear more uniform. Mesenchymal stem cell and protein attachment were the lowest on polymers grown from oxidised surfaces. PEG-containing brush-like polymers displayed lower protein attachment than surfaces conjugated with PEG using a previously reported "grafting to" method, but polymers containing zwitterionic side chains displayed both the lowest contact angles and the lowest cell and protein attachment. This finding may arise from the interactions of the zwitterionic pendant groups through their permanent dipoles and is an important finding because PEG is susceptible to oxidative damage that can reduce efficacy over time. These modified silk materials with lower cell and protein attachments are envisioned to find utility when enhanced diffusion around surfaces is required, such as in drug delivery implants.
家蚕丝素纤维是一种纤维状蛋白质，其可调的性质和生物相容性使其在多种应用中得到了应用，包括药物输送载体、伤口敷料和组织工程支架。控制蛋白质和细胞附着对生物材料的性能至关重要，但丝素纤维大多是疏水性的，与细胞和蛋白质非特异性相互作用。用亲水性聚合物对丝素进行功能化可以减少附着，但反应性位点少使得实现均匀的接枝一直是一个挑战。这项工作提出了一种从可降解丝膜表面生长刷状聚合物的新方法，其中膜富含羟基，用引发剂进行功能化，最后通过原子转移自由基聚合与丙烯酰胺单体反应。研究了两种不同的羟基富集途径，一种涉及与环氧乙烷（EO）反应，另一种使用两步光催化氧化反应。两种途径都增加了表面亲水性，并从表面聚合了含有非带电（聚乙二醇，PEG）侧基或两性离子侧基的亲水性单体。发现最初处理薄膜以诱导β-折叠结构会影响聚合的成功。与 EO 改性或未改性的丝素表面相比，氧化反应导致更多的聚合物接枝，并且表面看起来更均匀。与氧化表面生长的聚合物相比，间充质干细胞和蛋白质附着最低。含 PEG 的刷状聚合物的蛋白质附着比使用先前报道的“接枝到”方法接枝的 PEG 表面低，但含有两性离子侧链的聚合物表现出最低的接触角和最低的细胞和蛋白质附着。这一发现可能源于两性离子侧基通过其永久偶极子的相互作用，这是一个重要的发现，因为 PEG 容易受到氧化损伤，随着时间的推移会降低其效力。这些具有较低细胞和蛋白质附着的改性丝材料预计在需要增强表面周围扩散的情况下会有应用，例如在药物输送植入物中。
