Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats.
Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats.
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负载 bFGF 和 NGF 的肝素-泊洛沙姆热敏水凝胶增强糖尿病大鼠周围神经再生
DOI：
10.1016/j.biomaterials.2018.03.044
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发表时间：
2018-06
期刊：
影响因子：
14
通讯作者：
Xiao J
中科院分区：
文献类型：
--
作者：
Li R;Li Y;Wu Y;Zhao Y;Chen H;Yuan Y;Xu K;Zhang H;Lu Y;Wang J;Li X;Jia X;Xiao J
周围神经损伤（PNI）是社会的主要负担，治疗方案有限，新型生物材料有很大的潜力改变目前的治疗模式。随着慢性疾病如糖尿病（DM）患病率的上升，PNI的治疗变得更加复杂，只有少数研究提出适合DM周围神经再生的治疗方法。为DM神经结构和/或功能的恢复提供支持性环境，我们研制了一种新型热敏型肝素-波洛沙姆（HP）水凝胶，与碱性成纤维细胞生长因子（bFGF）和神经生长因子（NGF）共同递送，用于糖尿病大鼠坐骨神经挤压损伤。该递送载体不仅对大量生长因子（GFs）具有良好的亲和力，而且能够稳定地控制其释放，防止其在体外降解。在体内，与单独使用HP水凝胶或直接使用GFs相比，GFs-HP水凝胶处理更有效地促进雪旺细胞（SC）增殖，导致神经相关结构蛋白表达增加，增强轴突再生和髓鞘再生，改善运动功能恢复（均p<0.05）。我们的机制研究还表明，GFs-HP水凝胶的这些神经保护和神经再生作用可能与磷脂酰肌醇3激酶和蛋白激酶B （PI3K/Akt）、janus激酶/信号转导和转录激活因子3 （JAK/STAT3）、丝裂原激活的蛋白激酶激酶/细胞外信号调节激酶（MAPK/ERK）信号通路的激活有关。我们的工作为糖尿病患者周围神经再生提供了一个有希望的治疗选择。
Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p<0.05). Our mechanistic investigation also revealed that these neuroprotective and neuroregenerative effects of the GFs-HP hydrogel may be associated with activations of phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt), janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. Our work provides a promising therapy option for peripheral nerve regeneration in patients with DM.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
影响因子：
3
作者：
Chen H;Du J;Zhang Y;Barnes K;Jia X
通讯作者：
Jia X
影响因子：
1.8
作者：
Andrades, JA;Wu, LT;Becerra, J
通讯作者：
Becerra, J
影响因子：
82.9
作者：
Chang, Edward I.;Galvez, Michael G.;Gurtner, Geoffrey C.
通讯作者：
Gurtner, Geoffrey C.
影响因子：
9.7
作者：
Du, Jinrong;Liu, Jianheng;Wang, Xiumei
通讯作者：
Wang, Xiumei