In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds.

In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds.
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DOI:
10.1016/j.actbio.2016.09.026
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发表时间:
2016-12
期刊:
影响因子:
9.7
通讯作者:
Fabiilli, Mario L.
Fabiilli, Mario L.
中科院分区:
工程技术1区
文献类型:
--
作者:
Moncion, Alexander;Arlotta, Keith J.;O'Neill, Eric G.;Lin, Melissa;Mohr, Lily A.;Franceschi, Renny T.;Kripfgans, Oliver D.;Putnam, Andrew J.;Fabiilli, Mario L.

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时空可控释放生长因子(GFS)对血管生成等再生过程至关重要。一种常见的策略是将GF包裹在水凝胶中,通过扩散和/或凝胶降解(即水解和/或蛋白质分解)来控制释放。然而,简单的封装策略不能提供对GF释放的空间或时间控制,特别是植入后的非侵入性、按需控制释放。我们之前证明了在组织工程和GF输送应用中广泛使用的纤维蛋白水凝胶可以掺入全氟碳乳液,从而产生一种声响应性支架(ARS),这种支架可以通过聚焦超声波进行调制,特别是通过一种称为声滴蒸发的机制。本研究在体外和体内研究了ARS和超声特性对替代有效载荷(即荧光标记的葡聚糖)的控制释放和纤维蛋白降解的影响。超声辐照(2.5 MHz,峰值稀释压:8 Mpa,空间峰值时间平均强度:86.4 mW/cm2)使体外和体内ARSS释放的葡聚糖分别增加7.7倍和21.7倍。超声还可诱导ARS的形态改变。令人惊讶的是,即使没有注射促血管生成的GFs,ARS的血管密度也比纤维蛋白高2.9倍。这些结果证明了ARSS在产生组织再生的控制释放方面的潜在用途。
Spatiotemporally controlled release of growth factors (GFs) is critical for regenerative processes such as angiogenesis. A common strategy is to encapsulate the GF within hydrogels, with release being controlled via diffusion and/or gel degradation (i.e., hydrolysis and/or proteolysis). However, simple encapsulation strategies do not provide spatial or temporal control of GF delivery, especially non-invasive, on-demand controlled release post implantation. We previously demonstrated that fibrin hydrogels, which are widely used in tissue engineering and GF delivery applications, can be doped with perfluorocarbon emulsion, thus yielding an acoustically responsive scaffold (ARS) that can be modulated with focused ultrasound, specifically via a mechanism termed acoustic droplet vaporization. This study investigates the impact of ARS and ultrasound properties on controlled release of a surrogate payload (i.e., fluorescently-labeled dextran) and fibrin degradation in vitro and in vivo. Ultrasound exposure (2.5 MHz, peak rarefactional pressure: 8 MPa, spatial peak time average intensity: 86.4 mW/cm2), generated up to 7.7 and 21.7-fold increases in dextran release from the ARSs in vitro and in vivo, respectively. Ultrasound also induced morphological changes in the ARS. Surprisingly, up to 2.9-fold greater blood vessel density was observed in ARSs compared to fibrin when implanted subcutaneously, even without delivery of pro-angiogenic GFs. The results demonstrate the potential utility of ARSs in generating controlled release for tissue regeneration.
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