Functionalizing Fibrin Hydrogels with Thermally Responsive Oligonucleotide Tethers for On-Demand Delivery.
Functionalizing Fibrin Hydrogels with Thermally Responsive Oligonucleotide Tethers for On-Demand Delivery.
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DOI：
10.3390/bioengineering9010025
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发表时间：
2022-01-10
期刊：
影响因子：
--
通讯作者：
Wu BM
中科院分区：
文献类型：
--
作者：
Linsley CS;Sung K;White C;Abecunas CA;Tawil BJ;Wu BM
有有限数量的刺激响应性生物材料能够在特定位置和时间递送可定制剂量的治疗剂。这在组织工程和再生医学应用中尤其如此，其中可能期望刺激响应性生物材料也用作支架材料。因此，本研究的目的是设计一种传统的非刺激响应支架生物材料，使其具有热响应性，从而可用于按需给药应用。纤维素水凝胶经常用于组织工程和再生医学应用，并且它们使用来自因子XIII（FXIII）底物的肽用热不稳定的寡核苷酸系链官能化。在所研究的FXIII底物肽中，α 2-纤溶酶抑制剂肽具有最大的掺入效率，并且肽和寡核苷酸系链的缀合物通过酶活性成功地掺入纤维蛋白水凝胶中。具有荧光团模型药物或血小板衍生生长因子-BB（PDGF-BB）的单链补体寡核苷酸可以通过温度升高按需释放。这些结果表明，可用于功能化传统的非刺激响应性生物材料，适合按需给药系统（DDS）的策略。
There are a limited number of stimuli-responsive biomaterials that are capable of delivering customizable dosages of a therapeutic at a specific location and time. This is especially true in tissue engineering and regenerative medicine applications, where it may be desirable for the stimuli-responsive biomaterial to also serve as a scaffolding material. Therefore, the purpose of this study was to engineer a traditionally non-stimuli responsive scaffold biomaterial to be thermally responsive so it could be used for on-demand drug delivery applications. Fibrin hydrogels are frequently used for tissue engineering and regenerative medicine applications, and they were functionalized with thermally labile oligonucleotide tethers using peptides from substrates for factor XIII (FXIII). The alpha 2-plasmin inhibitor peptide had the greatest incorporation efficiency out of the FXIII substrate peptides studied, and conjugates of the peptide and oligonucleotide tethers were successfully incorporated into fibrin hydrogels via enzymatic activity. Single-strand complement oligo with either a fluorophore model drug or platelet-derived growth factor-BB (PDGF-BB) could be released on demand via temperature increases. These results demonstrate a strategy that can be used to functionalize traditionally non-stimuli responsive biomaterials suitable for on-demand drug delivery systems (DDS).
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