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微生物工程聚羟基烷酸酯在生物医学中的应用:对最新进展、瓶颈和解决方案的深入了解。

Biomedical applications of microbially engineered polyhydroxyalkanoates: an insight into recent advances, bottlenecks, and solutions.

机构信息

Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, Uttar Pradesh, 226028, India.

Department of Biotechnology, Engineering School of Lorena (EEL), University of São Paulo, Lorena, 12.602.810, Brazil.

出版信息

Appl Microbiol Biotechnol. 2019 Mar;103(5):2007-2032. doi: 10.1007/s00253-018-09604-y. Epub 2019 Jan 15.

DOI:10.1007/s00253-018-09604-y
PMID:30645689
Abstract

Biopolymeric polyhydroxyalkanoates (PHAs) are fabricated and accumulated by microbes under unbalanced growth conditions, primarily by diverse genera of bacteria. Over the last two decades, microbially engineered PHAs gained substantial interest worldwide owing to their promising wide-range uses in biomedical field as biopolymeric biomaterials. Because of non-hazardous disintegration products, preferred surface alterations, inherent biocompatibility, modifiable mechanical properties, cultivation support for cells, adhesion devoid of carcinogenic impacts, and controllable biodegradability, the PHAs like poly-3-hydroxybutyrate, 3-hydroxybutyrate and 3-hydroxyvalerate co-polymers, 3-hydroxybutyrate and 4-hydroxybutyrate co-polymers, etc., are available for various medical applications. These PHAs have been exploited to design in vivo implants like sutures as well as valves for direct tissue repairing as well as in regeneration devices like bone graft substitutes, nerve guides as well as cardiovascular patches, etc. Furthermore, they are also emerged as attractive candidates for developing effective/novel drug delivery systems because of their biocompatibility and biodegradability with the ability to deliver and release the drugs at a specific site in a controllable manner and, therefore widen the therapeutic window with reduced side effects. However, there still remain some bottlenecks related to PHA purity, mechanical properties, biodegradability, etc., that are need to be addressed so as to make PHAs a realistic biomaterial. In addition, innovative approaches like PHAs co-production with other value-added products, etc., must be developed currently for economical PHA production. This review provides an insight toward the recent advances, bottlenecks, and potential solutions for prospective biomedical applications of PHAs with conclusion that relatively little research/study has been performed presently toward the viability of PHAs as realistic biopolymeric biomaterials.

摘要

生物聚合高分子量聚羟基烷酸酯 (PHA) 是由微生物在不平衡生长条件下制造和积累的,主要由不同属的细菌产生。在过去的二十年中,由于其在生物医学领域作为生物聚合生物材料的广泛应用前景,微生物工程化的 PHAs 在全球范围内引起了极大的关注。由于其无危险的分解产物、优选的表面改性、固有生物相容性、可改性机械性能、对细胞的培养支持、无致癌影响的附着和可控的生物降解性,如聚-3-羟基丁酸酯、3-羟基丁酸酯和 3-羟基戊酸共聚物、3-羟基丁酸酯和 4-羟基丁酸共聚物等 PHAs 可用于各种医学应用。这些 PHAs 已被用于设计体内植入物,如缝线和直接组织修复的瓣膜,以及再生装置,如骨移植物替代品、神经引导物和心血管贴片等。此外,由于其生物相容性和可生物降解性以及在特定部位以可控方式输送和释放药物的能力,它们也成为有吸引力的候选药物输送系统,从而扩大了治疗窗口,减少了副作用。然而,仍然存在一些与 PHA 纯度、机械性能、生物降解性等相关的瓶颈问题需要解决,以使 PHAs 成为一种现实的生物材料。此外,目前必须开发创新方法,如与其他增值产品的 PHAs 共生产等,以实现经济高效的 PHA 生产。本综述提供了对 PHAs 在生物医学应用方面的最新进展、瓶颈和潜在解决方案的深入了解,并得出结论,目前对 PHAs 作为现实生物聚合生物材料的可行性的研究相对较少。

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