文章信息/Info

Title:

Study on the Repair of Articular Cartilage Defects by EDC/NHS Cross-linked Recombinant Collagen Hydrogel

文章編號(hào):

1674-3962(2024)04-0344-11

作者:

黃長瑾; 雷桓; 唐曉軍

1. 中國醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)學(xué)院 整形外科醫(yī)院，北京 100144 2. 西北大學(xué)化工學(xué)院，陜西 西安 710069 3. 西北大學(xué) 生物醫(yī)藥研究院，陜西 西安 710069

Author(s):

HUANG Changjin;  LEI Huan;  TANG Xiaojun

1. Hospital of Plastic and Reconstructive Surgery, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100144, China 2. College of Chemical Engineering, Northwestern University, Xi’an 710069,China 3. Institute of Biomedical Research, Northwestern University, Xi’an 710069, China

關(guān)鍵詞:

EDC/NHS; 交聯(lián); 重組膠原蛋白; 可注射水凝膠; 關(guān)節(jié)軟骨修復(fù)

Keywords:

EDC/NHS;  cross-linking;  recombinant collagen;  injectable hydrogel;  articular cartilage repair

分類號(hào):

R684;R318.08

DOI:

10.7502/j.issn.1674-3962.202401011

文獻(xiàn)標(biāo)志碼:

A

摘要:

關(guān)節(jié)軟骨損傷、缺損是一種常見且嚴(yán)峻的臨床挑戰(zhàn)，沒有有效的治療方法，基于膠原蛋白的水凝膠是軟骨組織工程的研究熱點(diǎn)之一，但在開發(fā)具有良好生物相容性且可安全交聯(lián)的膠原蛋白產(chǎn)品，并提高軟骨修復(fù)有效性方面仍然存在巨大挑戰(zhàn)。將重組Ⅰ型膠原蛋白和重組Ⅲ型膠原蛋白通過EDC/NHS交聯(lián)，制備了2種水凝膠，均表現(xiàn)出良好的三維孔隙結(jié)構(gòu)以及優(yōu)異的力學(xué)性能和可降解性。研究發(fā)現(xiàn)，重組Ⅰ型膠原蛋白水凝膠（Gel-Ⅰ）和重組Ⅲ型膠原蛋白水凝膠（Gel-Ⅲ）能促進(jìn)人骨髓間充質(zhì)干細(xì)胞（human bone�瞞arrow mesenchymal stem cell，HBMSCs）糖胺聚糖的分泌，Gel-Ⅰ可以顯著上調(diào)BMSC表達(dá)COLⅡ基因和SOX9基因，Gel-Ⅲ可以顯著上調(diào)SOX9基因表達(dá)。在兔子膝關(guān)節(jié)軟骨修復(fù)模型中，與對(duì)照組和Gel�并蠼M相比，Gel-Ⅰ組在骨體積大小方面表現(xiàn)出明顯優(yōu)勢，軟骨下骨已形成并有效恢復(fù)，小梁的數(shù)量和厚度最高，小梁分布更均勻，并且缺損處新軟骨厚度與相鄰軟骨厚度相同。因此，重組I型膠原蛋白水凝膠在軟骨修復(fù)有效性以及安全性方面具有極大的臨床應(yīng)用潛力。

Abstract:

Articular cartilage injuries and defects are a common and severe clinical challenge without effective treatment, and collagen-based hydrogels is a hotspot for cartilage tissue engineering, but there are still great challenges in developing collagen products with good biocompatibility and safe cross�瞝inking, and the effectiveness of cartilage repair needs improving. In this study, recombinant type I collagen and recombinant type III collagen were cross�瞝inked by EDC/NHS to prepare injectable hydrogels. The two hydrogels exhibited good three-dimensional pore structures, and excellent mechanical properties as well as degradability. It was found that recombinant type I collagen hydrogel (Gel-Ⅰ) and recombinant type III collagen hydrogel (Gel�并�) could promote the glycosaminoglycans secretion of HBMSCs. The effects of the hydrogels on the chondrogenic differentiation of BMSC were analyzed by RF�瞦PCR, and it was found that Gel-Ⅰ significantly up-regulated COLII gene and SOX9 gene, and Gel-Ⅲ significantly up-regulated SOX9 gene. In the rabbit knee articular cartilage repair model, compared with the blank and Gel-Ⅲ groups, Gel-Ⅰ group showed the significant advantage in bone volume size, subchondral bone had been formed and effectively restored, the number and thickness of trabeculae were the highest, the trabeculaes were more uniformly distributed, and the thickness of the new cartilage at the defect was the same as that of the neighbouring cartilage. In conclusion, recombinant type I collagen hydrogel has great potential for clinical application in terms of the effectiveness and safety of cartilage repair.