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3D 打印的富含软骨细胞的聚己内酯支架在移植前的成熟可改善工程化软骨替代物的性能和整合。

Maturation of 3D-Printed, Chondrocyte-Laden, Polycaprolactone-Based Scaffolds Prior to Transplantation Improves Engineered Cartilage Substitute Properties and Integration.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Osakidetza, Donostia University Hospital, San Sebastián, Spain.

Otorhinolaryngology and Head and Neck Surgery Group, Biodonostia Health Research Institute, San Sebastián, Spain.

出版信息

Cartilage. 2022 Dec;13(4):105-118. doi: 10.1177/19476035221127638. Epub 2022 Oct 15.

Abstract

OBJECTIVE

The surgical management of nasal septal defects due to perforations, malformations, congenital cartilage absence, traumatic defects, or tumors would benefit from availability of optimally matured septal cartilage substitutes. Here, we aimed to improve maturation of 3-dimensional (3D)-printed, cell-laden polycaprolactone (PCL)-based scaffolds and test their performance in a rabbit auricular cartilage model.

DESIGN

Rabbit auricular chondrocytes were isolated, cultured, and seeded on 3D-printed PCL scaffolds. The scaffolds were cultured for 21 days under standard culture media and normoxia or in prochondrogenic and hypoxia conditions, respectively. Cell-laden scaffolds (as well as acellular controls) were implanted into perichondrium pockets of New Zealand white rabbit ears ( = 5 per group) and followed up for 12 weeks. At study end point, the tissue-engineered scaffolds were extracted and tested by histological, immunohistochemical, mechanical, and biochemical assays.

RESULTS

Scaffolds previously matured under prochondrogenic hypoxic conditions showed superior mechanical properties as well as improved patterns of cartilage matrix deposition, chondrogenic gene expression (, , , ), and proteoglycan production , compared with scaffolds cultured in standard conditions.

CONCLUSIONS

maturation of engineered cartilage scaffolds under prochondrogenic conditions that better mimic the environment may be beneficial to improve functional properties of the engineered grafts. The proposed maturation strategy may also be of use for other tissue-engineered constructs and may ultimately impact survival and integration of the grafts in the damaged tissue microenvironment.

摘要

目的

由于穿孔、畸形、先天性软骨缺失、创伤性缺损或肿瘤导致的鼻中隔缺损的外科治疗将受益于可获得的最佳成熟鼻中隔软骨替代物。在这里,我们旨在改善 3 维(3D)打印、细胞负载聚己内酯(PCL)基支架的成熟度,并在兔耳廓软骨模型中测试其 性能。

设计

分离、培养兔耳廓软骨细胞,并接种于 3D 打印的 PCL 支架上。分别在标准培养条件下和常氧或拟软骨形成和低氧条件下培养支架 21 天。将细胞负载的支架(以及无细胞对照)植入新西兰白兔耳廓的软骨膜囊中(每组 = 5),并随访 12 周。在研究终点,提取组织工程支架并通过组织学、免疫组织化学、力学和生化检测进行测试。

结果

与在标准条件下培养的支架相比,先前在拟软骨形成的低氧条件下成熟的支架具有更好的机械性能,以及改善的软骨基质沉积、软骨形成基因表达(、、、)和糖胺聚糖产生模式 ,。

结论

在更能模拟 环境的拟软骨形成条件下对工程化软骨支架进行成熟可能有助于改善工程化移植物的功能特性。所提出的成熟策略也可能对其他组织工程化构建物有用,并最终影响移植物在受损组织微环境中的存活和整合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9515/9924975/94d274e2326f/10.1177_19476035221127638-fig1.jpg

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