Tissue-engineered nerve grafts using a scaffold-independent and injectable drug delivery system: a novel design with translational advantages
Tissue-engineered nerve grafts using a scaffold-independent and injectable drug delivery system: a novel design with translational advantages
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使用不依赖于支架的可注射药物输送系统进行组织工程神经移植：具有转化优势的新颖设计
DOI：
10.1088/1741-2552/ab17a0
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发表时间：
2019-04
影响因子：
4
通讯作者：
Cui Shusen
中科院分区：
文献类型：
--
作者：
Liu Yanxi;Yu Shuangjiang;Gu Xiaosong;Cao Rangjuan;Cui Shusen
目标。目前市售的神经导管在修复周围神经缺损方面的临床疗效尚不理想。尽管具有神经营养因子（NTFs）持续释放的组织工程神经移植物（TENGs）在实验上被证明比这些空白导管更有效，但仍然缺乏临床转化。NTFs通常通过吸附、特异性结合或其他结合技术固定在导管的支架材料上。这些基于支架的输送策略增加了导管制造的复杂性和成本，并且在选择不同药物方面缺乏灵活性。因此，为了促进临床翻译和商业化，我们使用支架独立给药系统（DDS）构建了TENG。的方法。本研究采用基于甲氧基聚（乙二醇）-b-聚（γ-乙基- l-谷氨酸）（mPEG-PELG）热敏水凝胶的不依赖支架的DDS，该水凝胶在体温下发生溶胶-凝胶转变。此外，我们还设计了一种填充神经生长因子（NGF）负载的mPEG-PELG的壳聚糖支架TENG，该支架在手术过程中注射后在腔内凝胶化，并作为药物释放导管填充剂。观察DDS的疗效和TENG的治疗效果。主要的结果。结果表明，加载NGF的mPEG-PELG可控制并持续释放生物活性NGF 28 d。当桥接10 mm大鼠坐骨神经间隙时，形态学、电生理和功能分析显示，释放NGF的TENG （Scaffold + NGF/mPEG-PELG）比普通支架和与全身输送NGF（每日肌内注射（IM））相结合的TENG获得了更好的再生效果，其效果与自体移植物相对相似。的意义。本研究提出了一种使用热敏水凝胶作为可注射植入物的TENG，可控制释放NGF，具有良好的治疗潜力和可翻译性。这种teng不需要对导管进行修饰，不需要复杂的预载或结合介质，因此在临床实践中可以方便地切换药物，并且由于药物传递系统的独立制备，大大简化了制造过程。
Objective. Currently commercially available nerve conduits have demonstrated suboptimal clinical efficacy in repairing peripheral nerve defects. Although tissue-engineered nerve grafts (TENGs) with sustained release of neurotrophic factors (NTFs) are experimentally proved to be more effective than these blank conduits, there remains a lack of clinical translation. NTFs are typically immobilized onto scaffold materials of the conduit via adsorption, specific binding or other incorporation techniques. These scaffold-based delivery strategies increase complexity and cost of conduit fabrication and lack flexibility in choosing different drugs. Therefore, to facilitate clinical translation and commercialization, we construct a TENG using a scaffold-independent drug delivery system (DDS). Approach. This study adopted a scaffold-independent DDS based on methoxy-poly (ethylene glycol)-b-poly(γ-ethyl-L-glutamate) (mPEG-PELG) thermosensitive hydrogels that undergo sol-to-gel transition at body temperature. In addition, TENG, a chitosan scaffold filled with nerve growth factor (NGF)-loaded mPEG-PELG that gel in the lumen upon injection during surgery and function as a drug-releasing conduit-filler, was designed. Subsequently, the efficacy of DDS and therapeutic effects of TENG were assessed. Main results. The results demonstrated that NGF-loaded mPEG-PELG controllably and sustainably released bioactive NGF for 28 d. When bridging a 10 mm rat sciatic nerve gap, the morphological, electrophysiological, and functional analyses revealed that NGF-releasing TENG (Scaffold + NGF/mPEG-PELG) achieved superior regenerative outcomes compared to plain scaffolds and those combined with systemic delivery of NGF (daily intramuscular injection (IM)), and its effects were relatively similar to autografts. Significance. This study has proposed a TENG using thermosensitive hydrogels as an injectable implant to controllably release NGF, which has promising therapeutic potential and translatability. Such TENGs obviate the need for conduit modification, complex preloading or binding mediators, therefore they allow the ease of drug switching in clinical practice and greatly simplify the manufacturing process due to the independent preparation of drug delivery system.
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影响因子：
--
作者：
Ramburrun P;Kumar P;Choonara YE;Bijukumar D;du Toit LC;Pillay V
通讯作者：
Pillay V
DOI：
10.1002/jbm.b.34020
发表时间：
2018-08
期刊：
Journal of biomedical materials research. Part B, Applied biomaterials
影响因子：
--
作者：
Yao Yao-Yao;Yi Cui;Yannan Zhao;Zhifeng Xiao;Xing Li;Sufang Han;Bing Chen;Yongxiang Fang;Piao Wang;J. Pan;Jianwu Dai
通讯作者：
Yao Yao-Yao;Yi Cui;Yannan Zhao;Zhifeng Xiao;Xing Li;Sufang Han;Bing Chen;Yongxiang Fang;Piao Wang;J. Pan;Jianwu Dai
DOI：
10.1002/jbm.a.36204
发表时间：
2018
期刊：
Journal of biomedical materials research. Part A
影响因子：
--
作者：
Tonya J Whitehead;Christian Oliver C. Avila;H. Sundararaghavan
通讯作者：
Tonya J Whitehead;Christian Oliver C. Avila;H. Sundararaghavan
影响因子：
14
作者：
Gomes, Eduardo D.;Mendes, Sofia S.;Salgado, Antonio J.
通讯作者：
Salgado, Antonio J.
DOI：
10.1016/j.colsurfb.2017.10.017
发表时间：
2017-12
期刊：
Colloids and surfaces. B, Biointerfaces
影响因子：
--
作者：
Hua Wu;Jiaoyan Liu;Qing Fang;Bo Xiao;Ying Wan
通讯作者：
Hua Wu;Jiaoyan Liu;Qing Fang;Bo Xiao;Ying Wan