Tuning the non-equilibrium state of a drug-encapsulated poly(ethylene glycol) hydrogel for stem and progenitor cell mobilization.
Tuning the non-equilibrium state of a drug-encapsulated poly(ethylene glycol) hydrogel for stem and progenitor cell mobilization.
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DOI：
10.1016/j.biomaterials.2010.11.021
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发表时间：
2011-03
期刊：
影响因子：
14
通讯作者：
Kong, Hyunjoon
中科院分区：
文献类型：
--
作者：
Liang, Youyun;Jensen, Tor W.;Roy, Edward J.;Cha, Chaenyung;DeVolder, Ross J.;Kohman, Richie E.;Zhang, Bao Zhong;Textor, Kyle B.;Rund, Lauretta A.;Schook, Lawrence B.;Tong, Yen Wah;Kong, Hyunjoon
关键词：
可注射和可生物降解的水凝胶已经越来越多地被研究用于各种分子治疗中的持续药物递送。然而，由于施加在软水凝胶上的局部组织压力，在注射部位获得所需的输送速率仍然是一个挑战。此外，刚度和降解速率的可控性通常有限，这是实现所需药物释放速率和治疗功效所需的关键因素。本研究提出了一种刚性和亚稳态的聚（乙二醇）二丙烯酸酯（PEGDA）-聚（乙烯亚胺）（PEI）水凝胶，其表现出的弹性模量相当于散装塑料材料，和可控的降解速率独立于其初始弹性模量。这种独特的刚度是从PEI的高度支化的结构中获得的，并且通过调节水凝胶的非平衡溶胀来实现降解速率的解耦可控性。此外，单次肌内施用粒细胞集落刺激因子（GCSF）包封的PEGDA-PEI水凝胶将单核细胞的动员延长至4天。与每日推注给药相比，还获得了更大产量的扩增的CD 34+和CD 31+内皮祖细胞（EPCs）。总的来说，在这项研究中创建的水凝胶将是有用的控制和持续交付的广泛的药物分子。
Injectable and biodegradable hydrogels have been increasingly studied for sustained drug delivery in various molecular therapies. However, it remains a challenge to attain desired delivery rate at injection sites due to local tissue pressures exerted on the soft hydrogels. Furthermore, there is often limited controllability of stiffness and degradation rates, which are key factors required for achieving desired drug release rate and therapeutic efficacy. This study presents a stiff and metastable poly(ethylene glycol) diacrylate (PEGDA)-poly(ethylene imine) (PEI) hydrogel which exhibits an elastic modulus equivalent to bulk plastic materials, and controllable degradation rate independent of its initial elastic modulus. Such unique stiffness was attained from the highly branched architecture of PEI, and the decoupled controllability of degradation rate was achieved by tuning the non-equilibrium swelling of the hydrogel. Furthermore, a single intramuscular administration of granulocyte colony stimulating factor (GCSF)-encapsulated PEGDA-PEI hydrogel extended the mobilization of mononuclear cells to four days. A larger yield of expanded CD34+ and CD31+ endothelial progenitor cells (EPCs) was also obtained as compared to the daily bolus administration. Overall, the hydrogel created in this study will be useful for the controlled and sustained delivery of a wide array of drug molecules.
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影响因子：
9.7
作者：
Layman, Hans;Sacasa, Marianne;Andreopoulos, Fotios M.
通讯作者：
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影响因子：
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作者：
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