Severs Liza J, Katta Anjali, Cates Lindsay N, Dewees Dane M, Hoagland Riana T, Horner Philip J, Hofstetter Christoph P, Khaing Zin Z
Department of Physiology and Biophysics, The University of Washington, Seattle, WA 98109, USA.
Department of Neurological Surgery, The University of Washington, Seattle, WA 98109, USA.
Polymers (Basel). 2024 Dec 20;16(24):3556. doi: 10.3390/polym16243556.
Spinal cord trauma leads to the destruction of the highly organized cytoarchitecture that carries information along the axis of the spinal column. Currently, there are no clinically accepted strategies that can help regenerate severed axons after spinal cord injury (SCI). Hydrogels are soft biomaterials with high water content that are widely used as scaffolds to interface with the central nervous system (CNS). Here, we examine a simple and reproducible method that results in consistently aligned fibrils within 3D matrices using thermally gelling biomimetic polymers. A collagen type I (Col)-based thermally gelling hydrogel system was used in combination with two other native extracellular matrix proteins: laminin I (LN) and hyaluronic acid (HA). Gelling kinetics for all gel types (Col, Col LN, Col HA) showed that at 37 °C, all three hydrogels formed gels consistently. A method of aspiration and ejection was used to produce Col-based hydrogels containing aligned fibrils. In vitro, embryonic spinal cord neurons survived and produced processes aligned to collagen fibrils. Next, we implanted either non-aligned or aligned hydrogels after a bilateral dorsal hemisection of the thoracic spinal cord at T7/T8. Pan neuronal antibody-positive fibrils were found within all implants; aligned hydrogels supported neurite growth along the parallel direction of the implanted hydrogels. Combined, our in vitro and in vivo data indicate that thermally gelling biomimetic hydrogels can produce aligned matrices through a method of aspiration and ejection, and this presents a novel platform for regenerative therapies for the CNS.
脊髓损伤会导致高度有序的细胞结构遭到破坏，而这种细胞结构负责沿脊柱轴线传递信息。目前，尚无临床上被认可的策略能够帮助脊髓损伤（SCI）后切断的轴突再生。水凝胶是一种含水量高的软生物材料，被广泛用作与中枢神经系统（CNS）对接的支架。在此，我们研究了一种简单且可重复的方法，该方法使用热凝胶仿生聚合物在三维基质中形成始终排列整齐的纤维。基于I型胶原蛋白（Col）的热凝胶水凝胶系统与另外两种天然细胞外基质蛋白：层粘连蛋白I（LN）和透明质酸（HA）结合使用。所有凝胶类型（Col、Col LN、Col HA）的凝胶动力学表明，在37°C时，这三种水凝胶均能始终如一地形成凝胶。采用抽吸和喷射的方法来制备含有排列整齐纤维的基于Col的水凝胶。在体外，胚胎脊髓神经元能够存活并产生与胶原纤维排列一致的突起。接下来，我们在T7/T8水平对胸段脊髓进行双侧背侧半横切术后植入未排列或排列整齐的水凝胶。在所有植入物中均发现泛神经元抗体阳性纤维；排列整齐的水凝胶支持神经突沿着植入水凝胶的平行方向生长。综合我们的体外和体内数据表明，热凝胶仿生水凝胶可以通过抽吸和喷射的方法产生排列整齐的基质，这为中枢神经系统的再生治疗提供了一个新的平台。
