Raia Nicole R, Partlow Benjamin P, McGill Meghan, Kimmerling Erica Palma, Ghezzi Chiara E, Kaplan David L
Department of Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA 02155, USA.
Department of Biomedical Engineering, Tufts University, 4 Colby St., Medford, MA 02155, USA.
Biomaterials. 2017 Jul;131:58-67. doi: 10.1016/j.biomaterials.2017.03.046. Epub 2017 Mar 27.
In this study, silk fibroin and hyaluronic acid (HA) were enzymatically crosslinked to form biocompatible composite hydrogels with tunable mechanical properties similar to that of native tissues. The formation of di-tyrosine crosslinks between silk fibroin proteins via horseradish peroxidase has resulted in a highly elastic hydrogel but exhibits time-dependent stiffening related to silk self-assembly and crystallization. Utilizing the same method of crosslinking, tyramine-substituted HA forms hydrophilic and bioactive hydrogels that tend to have limited mechanics and degrade rapidly. To address the limitations of these singular component scaffolds, HA was covalently crosslinked with silk, forming a composite hydrogel that exhibited both mechanical integrity and hydrophilicity. The composite hydrogels were assessed using unconfined compression and infrared spectroscopy to reveal of the physical properties over time in relation to polymer concentration. In addition, the hydrogels were characterized by enzymatic degradation and for cytotoxicity. Results showed that increasing HA concentration, decreased gelation time, increased degradation rate, and reduced changes that were observed over time in mechanics, water retention, and crystallization. These hydrogel composites provide a biologically relevant system with controllable temporal stiffening and elasticity, thus offering enhanced tunable scaffolds for short or long term applications in tissue engineering.
在本研究中，丝素蛋白和透明质酸（HA）通过酶促交联形成了具有与天然组织相似的可调机械性能的生物相容性复合水凝胶。通过辣根过氧化物酶在丝素蛋白之间形成二酪氨酸交联，产生了一种高弹性水凝胶，但表现出与丝自组装和结晶相关的时间依赖性硬化。利用相同的交联方法，酪胺取代的HA形成了亲水性和生物活性水凝胶，但其力学性能往往有限且降解迅速。为了解决这些单一成分支架的局限性，HA与丝共价交联，形成了一种兼具机械完整性和亲水性的复合水凝胶。使用无侧限压缩和红外光谱对复合水凝胶进行评估，以揭示其物理性质随时间与聚合物浓度的关系。此外，还对水凝胶进行了酶促降解和细胞毒性表征。结果表明，增加HA浓度会缩短凝胶化时间、提高降解速率，并减少在力学性能、保水性和结晶方面随时间观察到的变化。这些水凝胶复合材料提供了一个具有可控时间硬化和弹性的生物相关系统，从而为组织工程中的短期或长期应用提供了增强的可调支架。
