Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
Acta Biomater. 2019 Apr 15;89:95-103. doi: 10.1016/j.actbio.2019.03.023. Epub 2019 Mar 14.
Biological hydrogels (biogels) are selective barriers that restrict passage of harmful substances yet allow the rapid movement of nutrients and select cells. Current methods to modulate the barrier properties of biogels typically involve bulk changes in order to restrict diffusion by either steric hindrance or direct high-affinity interactions with microstructural constituents. Here, we introduce a third mechanism, based on antibody-based third party anchors that bind specific foreign species but form only weak and transient bonds with biogel constituents. The weak affinity to biogel constituents allows antibody anchors to quickly accumulate on the surface of specific foreign species and facilitates immobilization via multiple crosslinks with the biogel matrix. Using the basement membrane Matrigel® and a mixture of laminin/entactin, we demonstrate that antigen-specific, but not control, IgG and IgM efficiently immobilize a variety of individual nanoparticles. The addition of Salmonella typhimurium-binding IgG to biogel markedly reduced the invasion of these highly motile bacteria. These results underscore a generalized strategy through which the barrier properties of biogels can be readily tuned with molecular specificity against a diverse array of particulates. STATEMENT OF SIGNIFICANCE: Biological hydrogels (biogels) are essential in living systems to control the movement of cells and unwanted substances. However, current methods to control transport within biogels rely on altering the microstructure of the biogel matrix at a gross level, either by reducing the pore size to restrict passage through steric hindrance or by chemically modifying the matrix itself. Both methods are either nonspecific or not scalable. Here, we offer a new approach, based on weakly adhesive third-party molecular anchors, that allow for a variety of foreign entities to be trapped within a biogel simultaneously with exceptional potency and molecular specificity, without perturbing the bulk properties of the biogel. This strategy greatly increases our ability to control the properties of biogels at the nanoscale, including those used for wound healing or tissue engineering applications.
生物水凝胶（biogels）是选择性屏障，可限制有害物质的通过，同时允许营养物质和选定细胞的快速移动。目前调节生物凝胶屏障特性的方法通常涉及整体变化，通过空间位阻或与微观结构成分的直接高亲和力相互作用来限制扩散。在这里，我们引入了第三种机制，基于基于抗体的第三方锚定物，这些锚定物与特定的外来物种结合，但与生物凝胶成分仅形成弱而短暂的键。与生物凝胶成分的弱亲和力允许抗体锚定物快速积累在特定外来物种的表面，并通过与生物凝胶基质的多个交联来促进固定化。使用基底膜 Matrigel®和层粘连蛋白/entactin 的混合物，我们证明抗原特异性但不是对照 IgG 和 IgM 有效地固定各种单个纳米颗粒。向生物凝胶中添加沙门氏菌结合 IgG 可显着降低这些高迁移性细菌的入侵。这些结果强调了一种通用策略，通过该策略可以通过针对各种颗粒的分子特异性来轻松调整生物凝胶的屏障特性。
生物水凝胶（biogels）在生命系统中对于控制细胞和不需要的物质的运动至关重要。然而，目前控制生物凝胶内运输的方法依赖于在宏观水平上改变生物凝胶基质的微结构，要么通过空间位阻减小孔径来限制通过，要么通过化学修饰基质本身。这两种方法要么是非特异性的，要么是不可扩展的。在这里，我们提供了一种新的方法，基于弱粘性的第三方分子锚定物，该方法允许各种外来实体同时被捕获在生物凝胶中，同时具有卓越的效力和分子特异性，而不会破坏生物凝胶的整体性质。这种策略极大地提高了我们在纳米尺度上控制生物凝胶性质的能力，包括那些用于伤口愈合或组织工程应用的生物凝胶。
