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首页> 外文期刊>Acta biomaterialia >A novel therapeutic design of microporous-structured biopolymer scaffolds for drug loading and delivery
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A novel therapeutic design of microporous-structured biopolymer scaffolds for drug loading and delivery

机译：微孔结构生物聚合物支架用于药物装载和输送的新型治疗设计

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Three-dimensional (3-D) open-channeled scaffolds of biopolymers are a promising candidate matrix for tissue engineering. When scaffolds have the capacity to deliver bioactive molecules the potential for tissue regeneration should be greatly enhanced. In order to improve drug-delivery capacity, we exploit 3-D poly(lactic acid) (PLA) scaffolds by creating microporosity within the scaffold network. Macroporous channeled PLA with a controlled pore configuration was obtained by a robotic dispensing technique. In particular, a room temperature ionic liquid (RTIL) bearing hydrophilic counter-anions, such as OTf and Cl, was introduced to the biopolymer solution at varying ratios. The RTIL-biopolymer slurry was homogenized by ultrasonication, and then solidified through the robotic dispensing process, during which the biopolymer and RTIL formed a bicontinuous interpenetrating network. After ethanol wash-out treatment the RTIL was completely removed to leave highly microporous open channels throughout the PLA network. The resultant pore size was observed to be a few micrometers (average 2.43 μm) and microporosity was determined to be ～70%. The microporous surface was also shown to favor initial cell adhesion, stimulating cell anchorage on the microporous structure. Furthermore, in vivo tissue responses assessed in rat subcutaneous tissue revealed good tissue compatibility, with minimal inflammatory reactions, while gathering a larger population of fibroblastic cells than the non-microporous scaffolds, and even facilitating invasion of the cells within the microporous structure. The efficacy of the micropore networks generated within the 3-D scaffolds in loading and releasing therapeutic molecules was addressed using antibiotic sodium ampicillin and protein cytochrome C as model drugs. The microporous scaffolds exhibited significantly enhanced drug loading capacity: 4-5 times increase in ampicillin and 9-10 times increase in cytochrome C compared to the non-microporous scaffolds. The release of ampicillin loaded within the microporous scaffolds was initially fast (～85% for 1 week), and was then slowed down, showing a continual release up to a month. On the other hand, cytochrome C was shown to release in a highly sustainable manner over a month, without showing an initial burst release effect. This study provides a novel insight into the generation of 3-D biopolymer scaffolds with high performance in loading and delivery of biomolecules, facilitated by the creation of microporous channels through the scaffold network. The capacity to support tissue cells while in situ delivering drug molecules makes the current scaffolds potentially useful for therapeutic tissue engineering.
机译：生物聚合物的三维（3-D）开放通道支架是组织工程的有希望的候选基质。当支架具有传递生物活性分子的能力时，组织再生的潜力应大大提高。为了提高药物传递能力，我们通过在支架网络内产生微孔来利用3-D聚乳酸（PLA）支架。通过机器人点胶技术获得了具有受控孔结构的大孔通道PLA。特别地，将具有亲水性抗衡阴离子如OTf和Cl的室温离子液体（RTIL）以不同的比例引入生物聚合物溶液中。 RTIL-生物聚合物浆液通过超声进行均质处理，然后通过自动分配过程进行固化，在此过程中，生物聚合物和RTIL形成了双连续的互穿网络。乙醇冲洗处理后，将RTIL完全去除，从而在整个PLA网络中留下高度微孔的开放通道。观察到的最终孔径为几微米（平均2.43μm），微孔率约为70％。还显示了微孔表面有利于初始细胞粘附，刺激了细胞在微孔结构上的锚定。此外，在大鼠皮下组织中评估的体内组织反应显示出良好的组织相容性，具有最小的炎症反应，同时比非微孔支架聚集了更多的成纤维细胞，甚至促进了细胞在微孔结构内的侵袭。使用抗生素氨苄西林钠和蛋白质细胞色素C作为模型药物，可以研究在3-D支架内产生的微孔网络在加载和释放治疗分子中的功效。微孔支架表现出显着增强的载药量：与非微孔支架相比，氨苄西林增加4-5倍，细胞色素C增加9-10倍。最初在微孔支架中释放的氨苄青霉素释放较快（约85％达1周），然后减慢了速度，显示持续释放长达一个月。另一方面，显示细胞色素C在一个月内以高度可持续的方式释放，而没有显示出初始的爆发释放效果。这项研究为生成3-D生物聚合物支架提供了新的见解，该支架在生物分子的装载和递送方面具有高性能，并通过支架网络中的微孔通道的建立得以促进。在原位递送药物分子时支持组织细胞的能力使得当前的支架潜在地可用于治疗性组织工程。

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