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可喷涂的组织粘合剂,其生物降解性能经过调整,用于预防术后腹部粘连。

Sprayable tissue adhesive with biodegradation tuned for prevention of postoperative abdominal adhesions.

作者信息

Erdi Metecan, Rozyyev Selim, Balabhadrapatruni Manogna, Saruwatari Michele S, Daristotle John L, Ayyub Omar B, Sandler Anthony D, Kofinas Peter

机构信息

Department of Chemical and Biomolecular Engineering University of Maryland College Park Maryland USA.

Sheikh Zayed Institute for Pediatric Surgical Innovation, Joseph E. Robert Jr. Center for Surgical Care Children's National Medical Center Washington District of Columbia USA.

出版信息

Bioeng Transl Med. 2022 May 23;8(1):e10335. doi: 10.1002/btm2.10335. eCollection 2023 Jan.

Abstract

Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following postoperative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in situ tissue-conforming and tissue-adherent scaffolds with exceptional mechanical properties. While biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) have desirable strength, they exhibit bulk biodegradation rates and inflammatory profiles that limit their use as adhesion barriers and result in poor tissue adhesion. Here, viscoelastic poly(lactide-co-caprolactone) (PLCL) is used for its pertinent biodegradation mechanism. Because it degrades via surface erosion, spray deposited PLCL fibers can dissolve new connections formed by inflamed tissue, allowing them to function as an effective, durable, and easy-to-apply adhesion barrier. Degradation kinetics are tuned to match adhesion formation through the design of PLCL blends comprised of highly adhesive "low"-molecular weight (LMW) constituents in a mechanically robust "high"-molecular weight (HMW) matrix. In vitro studies demonstrate that blending LMW PLCL (30% w/v) with HMW PLCL (70% w/v) yields an anti-fibrotic yet tissue-adhesive polymer sealant with a 14-day erosion rate countering adhesion formation. PLCL blends additionally exhibit improved wet tissue adhesion strength (~10 kPa) over a 14-day period versus previously explored biodegradable polymer compositions, such as PLGA. In a mouse cecal ligation model, select PLCL blends significantly reduce abdominal adhesions severity versus no treatment and Seprafilm-treated controls.

摘要

粘连是致密的纤维桥,由于术后间皮损伤后不受控制的炎症而毗邻组织表面。Seprafilm中广泛使用的粘连屏障材料由于其机械性能差、降解速度快以及难以精确应用,往往无法防止横向瘢痕组织沉积。溶液吹纺(SBS)是一种聚合物纤维沉积技术,可用于放置具有出色机械性能的原位组织贴合和组织粘附支架。虽然聚乳酸-乙醇酸共聚物(PLGA)等可生物降解聚合物具有理想的强度,但它们表现出的整体生物降解速率和炎症特征限制了它们作为粘连屏障的用途,并导致组织粘附性差。在此,使用具有相关生物降解机制的粘弹性聚(丙交酯-己内酯)(PLCL)。由于它通过表面侵蚀降解,喷雾沉积的PLCL纤维可以溶解由发炎组织形成的新连接,使其能够作为一种有效、耐用且易于应用的粘连屏障发挥作用。通过设计由机械坚固的“高”分子量(HMW)基质中的高粘性“低”分子量(LMW)成分组成的PLCL共混物,调整降解动力学以匹配粘连形成。体外研究表明,将低分子量PLCL(30% w/v)与高分子量PLCL(70% w/v)混合可产生一种抗纤维化但具有组织粘附性的聚合物密封剂,其14天的侵蚀速率可对抗粘连形成。与先前探索的可生物降解聚合物组合物(如PLGA)相比,PLCL共混物在14天内还表现出更高的湿组织粘附强度(约10 kPa)。在小鼠盲肠结扎模型中,与未治疗和Seprafilm治疗的对照组相比,选择的PLCL共混物可显著降低腹部粘连的严重程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a425/9842025/838ce01ea1b1/BTM2-8-e10335-g003.jpg

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