Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea.
School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.
J Control Release. 2024 Apr;368:140-156. doi: 10.1016/j.jconrel.2024.02.017. Epub 2024 Feb 22.
Traumatic brain injuries(TBI) pose significant challenges to human health, specifically neurological disorders and related motor activities. After TBI, the injured neuronal tissue is known for hardly regenerated and recovered to their normal neuron physiology and tissue compositions. For this reason, tissue engineering strategies that promote neuronal regeneration have gained increasing attention. This study explored the development of a novel neural tissue regeneration cryogel by combining brain-derived decellularized extracellular matrix (ECM) with heparin sulfate crosslinking that can perform nerve growth factor (NGF) release ability. Morphological and mechanical characterizations of the cryogels were performed to assess their suitability as a neural regeneration platform. After that, the heparin concnentration dependent effects of varying NGF concentrations on cryogel were investigated for their controlled release and impact on neuronal cell differentiation. The results revealed a direct correlation between the concentration of released NGF and the heparin sulfate ratio in cryogel, indicating that the cryogel can be tailored to carry higher loads of NGF with heparin concentration in cryogel that induced higher neuronal cell differentiation ratio. Furthermore, the study evaluated the NGF loaded cryogels on neuronal cell proliferation and brain tissue regeneration in vivo. The in vivo results suggested that the NGF loaded brain ECM derived cryogel significantly affects the regeneration of brain tissue. Overall, this research contributes to the development of advanced neural tissue engineering strategies and provides valuable insights into the design of regenerative cryogels that can be customized for specific therapeutic applications.
创伤性脑损伤（TBI）对人类健康构成重大挑战，特别是神经紊乱和相关运动活动。TBI 后，受伤的神经元组织几乎无法再生并恢复到正常的神经元生理和组织组成。出于这个原因，促进神经元再生的组织工程策略引起了越来越多的关注。本研究通过将脑源去细胞化细胞外基质（ECM）与硫酸肝素交联相结合，探索了一种新型神经组织再生冷冻凝胶的开发，该凝胶具有神经生长因子（NGF）释放能力。对冷冻凝胶进行形态和机械特性分析，以评估其作为神经再生平台的适用性。之后，研究了肝素浓度依赖性变化对不同 NGF 浓度对冷冻凝胶的影响，以研究其对 NGF 的控制释放及其对神经元细胞分化的影响。结果表明，释放的 NGF 浓度与冷冻凝胶中硫酸肝素的比例之间存在直接相关性，表明可以根据肝素浓度对冷冻凝胶进行定制，以携带更高载量的 NGF，肝素浓度诱导更高的神经元细胞分化比例。此外，该研究还评估了负载 NGF 的冷冻凝胶对体内神经元细胞增殖和脑组织再生的影响。体内结果表明，负载 NGF 的脑 ECM 衍生冷冻凝胶对脑组织再生有显著影响。总的来说，这项研究为先进的神经组织工程策略的发展做出了贡献，并为可根据特定治疗应用进行定制的再生冷冻凝胶的设计提供了有价值的见解。
