Reed Stephanie, Wu Benjamin
UCLA, Los Angeles, CA, USA.
Ann Biomed Eng. 2014 Jul;42(7):1528-36. doi: 10.1007/s10439-013-0956-6. Epub 2013 Dec 7.
The beautifully orchestrated complexity of the temporal spatial growth factor gradients during embryogenesis offer a striking contrast to systemic bolus administration that lack tissue specificity and sustained protein localization, often requiring supraphysiological protein doses to produce the desired therapeutic dose. These attributes may be responsible for clinically observed dangerous tissue overgrowth, inflammation, and even tumor formation. Growth factor delivery within an implanted scaffold is a very attractive way to modulate cell behavior. For short term delivery, proteins can be non-specifically adsorbed to the material surface or simply entrapped within the bulk scaffold. For more sustained delivery, many researchers have turned to the ever increasing list of covalent immobilization methods that have profound applications in purification, biosensing, imaging, and drug discovery by tethering proteins, nucleic acids, carbohydrates, synthetic polymers, small molecules, nanotubes, and even whole cells. This review focuses on the use of covalent immobilization to achieve sustained growth factor delivery for tissue engineering. Covalent immobilization techniques will be reviewed in terms of design, protein bioactivity/stability, efficiency, and spatiotemporal distribution. Further, the biological response to sustained growth factor delivery will also be covered, such as cell interaction, cell responsiveness, proliferation, differentiation, extracellular matrix production, and tissue regeneration. This focused review is anticipated to inform investigators on the selection of optimal immobilization strategies for their specific applications.
胚胎发育过程中时空生长因子梯度精妙协调的复杂性，与全身推注给药形成了鲜明对比。全身推注给药缺乏组织特异性且蛋白质定位不持久，往往需要超生理剂量的蛋白质才能产生所需的治疗剂量。这些特性可能是临床上观察到的危险组织过度生长、炎症甚至肿瘤形成的原因。在植入支架内递送生长因子是调节细胞行为的一种非常有吸引力的方式。对于短期递送，蛋白质可以非特异性地吸附在材料表面或简单地包埋在整体支架内。对于更持久的递送，许多研究人员已转向越来越多的共价固定方法，这些方法通过连接蛋白质、核酸、碳水化合物、合成聚合物、小分子、纳米管甚至整个细胞，在纯化、生物传感、成像和药物发现中有着广泛应用。本综述重点关注利用共价固定实现用于组织工程的生长因子持续递送。将从设计、蛋白质生物活性/稳定性、效率和时空分布等方面对共价固定技术进行综述。此外，还将涵盖对生长因子持续递送的生物学反应，如细胞相互作用、细胞反应性、增殖、分化、细胞外基质产生和组织再生。这篇重点综述预计将为研究人员在为其特定应用选择最佳固定策略时提供参考。
