Controlled release of basic fibroblast growth factor for angiogenesis using acoustically-responsive scaffolds.

Controlled release of basic fibroblast growth factor for angiogenesis using acoustically-responsive scaffolds.
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DOI:
10.1016/j.biomaterials.2017.06.012
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发表时间:
2017-09
期刊:
影响因子:
14
通讯作者:
Fabiilli ML
Fabiilli ML
中科院分区:
工程技术1区
文献类型:
--
作者:
Moncion A;Lin M;O'Neill EG;Franceschi RT;Kripfgans OD;Putnam AJ;Fabiilli ML

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由于安全性和有效性的考虑,促血管生成生长因子用于治疗血管疾病的临床翻译仍然是一个挑战。不同的方法被用来设计时空控制的生长因子递送系统,以便概括内源信号的各个方面,从而帮助翻译。我们已经开发了声响响应型支架(ARS),这是一种掺入含有有效载荷的声敏乳剂的纤维蛋白支架。有效载荷的释放可以使用聚焦的兆赫范围超声(US)以非侵入性和按需的方式进行控制。在这项研究中,我们研究了单分散乳剂中含有碱性成纤维细胞生长因子的ARSS的体外和体内释放情况。利用具有流动聚焦几何结构的微流控装置,在两步过程中产生乳状液。在2.5 MHz频率下,当超声压力大于2.2±0.2 Mpa时,可观察到碱性成纤维细胞生长因子的控释。超阈值超声可使bFGF的体外释放增加12.6倍。并对释放的碱性成纤维细胞生长因子的生物活性进行了表征。当移植到小鼠的皮下时,暴露在超阈值超声下的ARS显示出比没有暴露于US的ARS分别高3.3倍和1.7倍的灌注量和血管密度。支架的降解不受美国的影响。这些结果突出了ARSS在治疗性血管生成的基础和应用研究中的实用性。
The clinical translation of pro-angiogenic growth factors for treatment of vascular disease has remained a challenge due to safety and efficacy concerns. Various approaches have been used to design spatiotemporally-controlled delivery systems for growth factors in order to recapitulate aspects of endogenous signaling and thus assist in translation. We have developed acoustically-responsive scaffolds (ARSs), which are fibrin scaffolds doped with a payload-containing, sonosensitive emulsion. Payload release can be controlled non-invasively and in an on-demand manner using focused, megahertz-range ultrasound (US). In this study, we investigate the in vitro and in vivo release from ARSs containing basic fibroblast growth factor (bFGF) encapsulated in monodispersed emulsions. Emulsions were generated in a two-step process utilizing a microfluidic device with a flow focusing geometry. At 2.5 MHz, controlled release of bFGF was observed for US pressures above 2.2 ± 0.2 MPa peak rarefactional pressure. Superthreshold US yielded a 12.6-fold increase in bFGF release in vitro. The bioactivity of the released bFGF was also characterized. When implanted subcutaneously in mice, ARS exposed to superthreshold US displayed up to 3.3-fold and 1.7-fold greater perfusion and blood vessel density, respectively, than ARS without US exposure. Scaffold degradation was not impacted by US. These results highlight the utility of ARSs in both basic and applied studies of therapeutic angiogenesis.
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