In vivo bioresponses to silk proteins.
In vivo bioresponses to silk proteins.
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DOI：
10.1016/j.biomaterials.2015.08.039
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发表时间：
2015-12
期刊：
影响因子：
14
通讯作者：
Kaplan DL
中科院分区：
文献类型：
--
作者：
Thurber AE;Omenetto FG;Kaplan DL
由于丝具有可调的机械性能和广泛的物理结构，因此丝是许多生物医学应用的吸引人的材料，包括药物递送、组织工程或可植入装置。除了特定临床应用所需的功能外，任何植入材料临床成功的关键因素是与体内身体的适当相互作用。这篇综述总结了我们目前对蚕丝的体内生物学反应的理解，包括降解，免疫和炎症反应，以及组织重塑，特别注意血管化。由于蚕丝丝素蛋白在医疗材料和消费品中的广泛应用，我们将重点放在蚕丝丝素蛋白上，因为有大量的体内数据，蜘蛛丝信息也包括在内。丝蛋白在体内降解的时间过程取决于丝的制造方法，可以从几小时到几年不等。丝蛋白通常诱导轻度炎症反应，在植入后几周内减少。该反应涉及巨噬细胞的募集和活化，并可能包括轻度异物反应的活化，形成多核巨细胞，这取决于植入的材料形式和位置。存在的免疫细胞的数量随着时间的推移而减少，并且肉芽组织（如果形成的话）被内源性组织而不是纤维组织所取代。重要的是，丝材料尚未被证明诱导矿化，除非用于钙化组织。由于其降解能力，丝可以在体内重塑，允许血管化和组织向内生长，最终被天然组织完全替代。重塑、组织向内生长或其他特定细胞行为的程度可以通过添加生长或其他信号传导因子来调节。丝绸还可以与许多其他材料结合，包括蛋白质，合成聚合物和陶瓷，以增强其特定功能的特性。总体而言，多种多样的丝材料显示出优异的体内生物反应，具有低免疫原性和被天然组织重塑和替代的能力，使其适用于许多临床应用。
Silks are appealing materials for numerous biomedical applications involving drug delivery, tissue engineering, or implantable devices, because of their tunable mechanical properties and wide range of physical structures. In addition to the functionalities needed for specific clinical applications, a key factor necessary for clinical success for any implanted material is appropriate interactions with the body in vivo. This review summarizes our current understanding of the in vivo biological responses to silks, including degradation, the immune and inflammatory response, and tissue remodeling with particular attention to vascularization. While we focus in this review on silkworm silk fibroin protein due to the large quantity of in vivo data thanks to its widespread use in medical materials and consumer products, spider silk information is also included if available. Silk proteins are degraded in the body on a time course that is dependent on the method of silk fabrication and can range from hours to years. Silk protein typically induces a mild inflammatory response that decreases within a few weeks of implantation. The response involves recruitment and activation of macrophages and may include activation of a mild foreign body response with the formation of multinuclear giant cells, depending on the material format and location of implantation. The number of immune cells present decreases with time and granulation tissue, if formed, is replaced by endogenous, not fibrous, tissue. Importantly, silk materials have not been demonstrated to induce mineralization, except when used in calcified tissues. Due to its ability to be degraded, silk can be remodeled in the body allowing for vascularization and tissue ingrowth with eventual complete replacement by native tissue. The degree of remodeling, tissue ingrowth, or other specific cell behaviors can be modulated with addition of growth or other signaling factors. Silk can also be combined with numerous other materials including proteins, synthetic polymers, and ceramics to enhance its characteristics for a particular function. Overall, the diverse array of silk materials shows excellent bioresponses in vivo with low immunogenicity and the ability to be remodeled and replaced by native tissue making it suitable for numerous clinical applications.