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生物聚合物3D打印支架作为先天性膈疝的一种通用组织工程治疗方法。

Biopolymeric 3D printed scaffolds as a versatile tissue engineering treatment for congenital diaphragmatic hernia.

作者信息

Dedeloudi Aikaterini, Farzeen Fatima, Lesutan Vlad-Nicolae, Irwin Robyn, Wylie Matthew P, Andersen Sune, Eastwood Mary Patrice, Lamprou Dimitrios A

机构信息

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

Johnson & Johnson Innovative Medicine, Oral Solids Development, Research & Development, Turnhoutseweg 30, 2340 Beerse, Belgium.

出版信息

Int J Pharm. 2025 Mar 15;672:125313. doi: 10.1016/j.ijpharm.2025.125313. Epub 2025 Feb 2.

Abstract

Congenital diaphragmatic hernia (CDH) is a rare disease in which neonates are born with pulmonary hypoplasia and a diaphragmatic defect. Survival is improving due to advances in fetal intervention for pulmonary hypoplasia leading to increased use of scaffolds for repair. Scaffolds have a significant morbidity rate with recurrence, small bowel obstruction and infrequently postoperative infections. 3D printing (3DP) is a promising technology for the fabrication of personalized medical devices characterised by a more precise and targeted approach to tissue engineering and drug delivery. In this study, blank thermoplastic polyurethane (TPU) and gentamicin sulfate (GNS)-loaded filaments (1 % and 1.5 %wt.) were fabricated with hot melt extrusion (HME) and subsequently processed through 3DP for scaffold manufacturing. Geometrical attributes of the scaffolds, including a specific % infill, were predefined through computer aided design (CAD) and printing parameters were optimised. Physicochemical analysis involving material compatibility and thermal properties of all formulations were examined, determining their thermal and chemical stability during 3DP. Mechanical analysis showed that polymeric matrixes resemble to diaphragm tissue, exhibiting adequate and reproducible elastic performance, while cell studies confirmed TPU's supportive capacity for cellular attachment. Additionally, in vitro dissolution and bacterial studies were carried out for up to a week, denoting GNS's sustained release from the polymeric matrices and efficient bactericidal activity to Gram-positive and Gram-negative bacteria, respectively. Therefore, TPU is a potential biomaterial that can be efficiently used for developing diverse 3D printed diaphragm-like scaffolds possessing antimicrobial activity for CDH.

摘要

先天性膈疝(CDH)是一种罕见疾病,新生儿出生时伴有肺发育不全和膈肌缺损。由于胎儿干预治疗肺发育不全方面的进展,存活率有所提高,这导致修复用支架的使用增加。支架存在显著的发病率,包括复发、小肠梗阻,术后感染也不常见。3D打印(3DP)是一种很有前景的技术,可用于制造个性化医疗设备,其特点是在组织工程和药物递送方面采用更精确、更有针对性的方法。在本研究中,采用热熔挤出(HME)制备了空白热塑性聚氨酯(TPU)和负载硫酸庆大霉素(GNS)的长丝(1%和1.5%重量),随后通过3D打印进行支架制造。通过计算机辅助设计(CAD)预先定义了支架的几何属性,包括特定的填充率,并优化了打印参数。对所有配方进行了包括材料相容性和热性能在内的物理化学分析,确定了它们在3D打印过程中的热稳定性和化学稳定性。力学分析表明,聚合物基体类似于膈肌组织,具有足够且可重复的弹性性能,而细胞研究证实了TPU对细胞附着的支持能力。此外,进行了长达一周的体外溶解和细菌研究,结果表明GNS能从聚合物基体中持续释放,并且分别对革兰氏阳性菌和革兰氏阴性菌具有高效杀菌活性。因此,TPU是一种潜在的生物材料,可有效地用于开发具有抗菌活性的多种3D打印膈肌样支架,用于治疗先天性膈疝。

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