Grier William K, Iyoha Ehiremen M, Harley Brendan A C
Dept. of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Dept. of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
J Mech Behav Biomed Mater. 2017 Jan;65:295-305. doi: 10.1016/j.jmbbm.2016.08.034. Epub 2016 Aug 29.
Orthopedic injuries, particularly those involving tendons and ligaments, are some of the most commonly treated musculoskeletal ailments, but are associated with high costs and poor outcomes. A significant barrier in the design of biomaterials for tendon tissue engineering is the rapid de-differentiation observed for primary tenocytes once removed from the tendon body. Herein, we evaluate the use of an anisotropic collagen-glycosaminoglycan (CG) scaffold as a tendon regeneration platform. We report the effects of structural properties of the scaffold (pore size, collagen fiber crosslinking density) on resultant tenocyte bioactivity, viability, and gene expression. In doing so we address a standing hypothesis that scaffold anisotropy and strut flexural rigidity (stiffness) co-regulate long-term maintenance of a tenocyte phenotype. We report changes in equine tenocyte specific gene expression profiles and bioactivity across a homologous series of anisotropic collagen scaffolds with defined changes in pore size and crosslinking density. Anisotropic scaffolds with higher crosslinking densities and smaller pore sizes were more able to resist cell-mediated contraction forces, promote increased tenocyte metabolic activity, and maintain and increase expression of tenogenic gene expression profiles. These results suggest that control over scaffold strut flexural rigidity via crosslinking and porosity provides an ideal framework to resolve structure-function maps relating the influence of scaffold anisotropy, stiffness, and nutrient biotransport on tenocyte-mediated scaffold remodeling and long-term phenotype maintenance.
骨科损伤，尤其是涉及肌腱和韧带的损伤，是最常见的肌肉骨骼疾病之一，但治疗成本高昂且预后不佳。肌腱组织工程生物材料设计中的一个重大障碍是，原代肌腱细胞一旦从肌腱主体中取出，就会迅速去分化。在此，我们评估了一种各向异性胶原-糖胺聚糖（CG）支架作为肌腱再生平台的用途。我们报告了支架的结构特性（孔径、胶原纤维交联密度）对所得肌腱细胞生物活性、活力和基因表达的影响。在此过程中，我们验证了一个长期存在的假设，即支架各向异性和支柱弯曲刚度（硬度）共同调节肌腱细胞表型的长期维持。我们报告了马肌腱细胞特异性基因表达谱和生物活性在一系列具有特定孔径和交联密度变化的各向异性胶原支架中的变化情况。具有较高交联密度和较小孔径的各向异性支架更能抵抗细胞介导的收缩力，促进肌腱细胞代谢活性增加，并维持和增加肌腱生成基因表达谱的表达。这些结果表明，通过交联和孔隙率控制支架支柱弯曲刚度，为解析与支架各向异性、硬度和营养物质生物转运对肌腱细胞介导的支架重塑和长期表型维持的影响相关的结构-功能图谱提供了一个理想的框架。
