Application of biomaterials in rotator cuff injury based on animal models

doi:10.3877/cma.j.issn.1674-134X.2024.01.015

Abstract

Abstract:

Rotator cuff injury can be produced by various external or internal factors such as trauma, subacromial impingement, and degeneration. Patients with rotator cuff injuries typically experience local pain and functional limitations. At the moment, rotator cuff injuries are often treated surgically, and the majority of patients experience increased function following surgery, but there is a high risk of the repaired tissue rupturing again. Orthopedic soft tissue restoration has a lot of potential with the development of tissue engineering materials. This article evaluated the preclinical research literature, listed the most often employed animal types, discussed their benefits and drawbacks in relation to the pathological rotator cuff injury alterations, and examined prominent rotator cuff repair biomaterials. In order to hasten the translation of clinical investigations, it intended to serve as a reference for preclinical animal experiments.

Key words: Rotator cuff injuries, Biocompatible materials, Models, animal

Dijun Li, Bin Wang. Application of biomaterials in rotator cuff injury based on animal models[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2024, 18(01): 118-124.

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Figures/Tables 4

References 60

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动物种类	优点	缺点
小鼠	成本低，繁殖快，容易管理，明显抗感染能力	体型小操作难度大，自愈能力强
大鼠	成本低、繁殖快、易于管理，肩部解剖结构与人相似，更容易做与损伤相关的指标测试	自愈能力强，肩部形态不算大，有一定操作难度，术后观察困难
兔	操作方便；冈上肌腱的形态与人类较为相似；肌腱离断后存在与人类相似的脂肪浸润过程	自愈能力较强；易遭受惊吓或腹泻，造成二次受伤和死亡
犬	肩袖承受机械载荷与人类相当，具有相似的生物力学环境；操作简单	购买和饲养成本较高，肩部解剖学结构与人类有较大差异
羊、牛	解剖结构明显，手术操作更加方便	饲养和管理成本高
灵长类	肩部结构在解剖学、组织学、生物力学及免疫学与人类更相似	购买和饲养成本更高，伦理要求更严格

动物种类	优点	缺点
小鼠	成本低，繁殖快，容易管理，明显抗感染能力	体型小操作难度大，自愈能力强
大鼠	成本低、繁殖快、易于管理，肩部解剖结构与人相似，更容易做与损伤相关的指标测试	自愈能力强，肩部形态不算大，有一定操作难度，术后观察困难
兔	操作方便；冈上肌腱的形态与人类较为相似；肌腱离断后存在与人类相似的脂肪浸润过程	自愈能力较强；易遭受惊吓或腹泻，造成二次受伤和死亡
犬	肩袖承受机械载荷与人类相当，具有相似的生物力学环境；操作简单	购买和饲养成本较高，肩部解剖学结构与人类有较大差异
羊、牛	解剖结构明显，手术操作更加方便	饲养和管理成本高
灵长类	肩部结构在解剖学、组织学、生物力学及免疫学与人类更相似	购买和饲养成本更高，伦理要求更严格

作者及年份	研究材料	动物模型	研究结果
Oame 2012^[26]	脱细胞肌腱切片＋骨髓间质细胞	兔	与无骨髓间充质干细胞的肌腱切片相比，细胞种子复合材料中肌腱调节蛋白、Ⅲ型胶原、MMP3和MMP13表达升高，Ⅰ型胶原表达较低。骨髓间充质干细胞可以在多层复合材料中存活，表达一种肌腱表型，并在体内增强肌腱的代谢
Ide 2009^[11]	无细胞真皮基质补片	大鼠	无细胞真皮基质补片组的标本比对照组的标本肌腱成熟评分更高，显示出更高的生物力学性能
Lee 2017^[12]	脱细胞尸体真皮基质＋重组人骨形成蛋白2	兔	使用富含重组人骨形成蛋白2涂层的脱细胞真皮补片不仅显著改善了新骨的形成，还改善了肌腱极限抗拉强度等生物力学性能
Smith 2020^[27]	牛胶原补片、脱细胞异种真皮基质、羊膜基质支架	犬	与对照组相比较，生物支架可以有效地促进冈上肌腱撕裂的愈合。且脱细胞的人同种异体真皮基质和羊膜基质支架可能比牛胶原蛋白补片更有优势
Hee 2011^[28]	重组人血小板源样生长因子-BB＋I型胶原基质	羊	与对照组比较，观察到最终失败负荷显著增加，在组织学上也表现出肌腱－骨的增加，能够改善羊肩袖修复模型的生物力学强度和解剖外观
Peterson 2015^[29]	肽碱性成纤维细胞生长因子模拟物＋Ⅰ胶原涂层	羊	在经过处理的绵羊中，富含更多的肌腱样修复组织，同时力学性能更强。新的支架和肽生长因子能有效地改善肌腱愈合
Learn 2019^[30]	电化学排列的胶原蛋白线编织生物纺织支架＋间充质干细胞	兔	所有组生物力学性能提高，富含干细胞组具有更高硬度。与天然肌腱相比，所有支架组细胞都增加。免疫组化显示所有组均存在Ⅰ和Ⅲ型胶原
Sevivas 2018^[31]	电纺角蛋白基支架＋间充质干细胞	大鼠	细胞能够在体外支架中保持很好的活力及密度。实验中发现组织学及生物力学性能得到明显改善
Zhu 2019^[24]	胶原支架	大鼠	胶原支架在体外可促进人肌腱来源细胞的增殖生长。与对照组比较，在体内使用支架改善了组织学评分，但是在力学检测效果差异无统计学意义

作者及年份	研究材料	动物模型	研究结果
Oame 2012^[26]	脱细胞肌腱切片＋骨髓间质细胞	兔	与无骨髓间充质干细胞的肌腱切片相比，细胞种子复合材料中肌腱调节蛋白、Ⅲ型胶原、MMP3和MMP13表达升高，Ⅰ型胶原表达较低。骨髓间充质干细胞可以在多层复合材料中存活，表达一种肌腱表型，并在体内增强肌腱的代谢
Ide 2009^[11]	无细胞真皮基质补片	大鼠	无细胞真皮基质补片组的标本比对照组的标本肌腱成熟评分更高，显示出更高的生物力学性能
Lee 2017^[12]	脱细胞尸体真皮基质＋重组人骨形成蛋白2	兔	使用富含重组人骨形成蛋白2涂层的脱细胞真皮补片不仅显著改善了新骨的形成，还改善了肌腱极限抗拉强度等生物力学性能
Smith 2020^[27]	牛胶原补片、脱细胞异种真皮基质、羊膜基质支架	犬	与对照组相比较，生物支架可以有效地促进冈上肌腱撕裂的愈合。且脱细胞的人同种异体真皮基质和羊膜基质支架可能比牛胶原蛋白补片更有优势
Hee 2011^[28]	重组人血小板源样生长因子-BB＋I型胶原基质	羊	与对照组比较，观察到最终失败负荷显著增加，在组织学上也表现出肌腱－骨的增加，能够改善羊肩袖修复模型的生物力学强度和解剖外观
Peterson 2015^[29]	肽碱性成纤维细胞生长因子模拟物＋Ⅰ胶原涂层	羊	在经过处理的绵羊中，富含更多的肌腱样修复组织，同时力学性能更强。新的支架和肽生长因子能有效地改善肌腱愈合
Learn 2019^[30]	电化学排列的胶原蛋白线编织生物纺织支架＋间充质干细胞	兔	所有组生物力学性能提高，富含干细胞组具有更高硬度。与天然肌腱相比，所有支架组细胞都增加。免疫组化显示所有组均存在Ⅰ和Ⅲ型胶原
Sevivas 2018^[31]	电纺角蛋白基支架＋间充质干细胞	大鼠	细胞能够在体外支架中保持很好的活力及密度。实验中发现组织学及生物力学性能得到明显改善
Zhu 2019^[24]	胶原支架	大鼠	胶原支架在体外可促进人肌腱来源细胞的增殖生长。与对照组比较，在体内使用支架改善了组织学评分，但是在力学检测效果差异无统计学意义

作者、年份	研究材料	动物模型	研究结果
Reifenrath 2020^[36]	电纺壳聚糖包覆的聚己聚糖纤维支架＋转化生长因子-β3	大鼠	与未负载转化生长因子-β3支架比较，负载该因子的支架生物力学更接近天然肌腱组织，组织学差异不大
Huang 2020^[37]	核原蛋白＋明胶甲基丙烯酰水凝胶支架	兔	修复肌腱的最终失效负荷和刚度均有所增加。软骨再生得到改善，在肌腱成熟评分更高
Romeo 2021^[38]	聚乙醇酸－聚乳酸共ε己内酯	羊	与对照组相比，支架治疗组显示类似于羊冈下肌腱的天然纤维软骨，存在明显的胶原纤维。生物力学显示支架治疗组最终失效负荷显著增加
Sun 2016^[34]	聚乳酸－羟基乙酸＋I型胶原＋聚己内酯	兔	在共电纺双纳米支架上接种成纤维细胞显示出更高的活力和胶原分泌，细胞具有更好矿化率。再生肌腱在12周时，共电纺双纳米支架的最大失效负荷与极限应力明显高于对照组
Tarafder 2019^[39]	聚乳酸－羟基乙酸＋聚己内酯＋细胞因子	大鼠	在体外支架成功地引导了间充质干细胞的区域分化，形成了具有肌腱样、软骨样和骨样区域的多相组织。在动物体内促进肌腱和骨的整合愈合
Su 2019^[40]	氧化石墨烯＋聚乳酸－羟基乙酸	兔	体外实验中加速了骨髓间充质干细胞的增殖，促进了骨髓间充质干细胞的成骨分化。在体内增加新骨和软骨生成，改善胶原蛋白排列和生物力学性能
Zhao 2014^[41]	聚乳酸－羟基乙酸＋b成纤维细胞生长因子	大鼠	与对照组相比，显著改善胶原蛋白组织，显著增加糖胺聚糖面积。生物力学显示静电纺丝纤维膜组比对照组有更大的最终失效负荷和刚度
Lipner 2015^[42]	聚乳酸－羟基乙酸＋脂肪间充质干细胞＋骨形态发生蛋白2	大鼠	组织学上，所有组的愈合界面均以纤维血管瘢痕反应为主。但是与其他组相比，负载骨形态发生蛋白2的细胞支架组生物力学性能下降
Kimura 2003^[32]	聚四氟乙烯	犬	组织学分析显示，聚四氟乙烯纤维之间有纤维组织的生长。但在12～24周期间，在聚四氟乙烯－骨界面的边缘发现了异物反应
Huegel 2017^[43]	聚己内酯＋自体肌腱细胞	大鼠	治疗组显示出细胞数量增加，胶原蛋白组织增加，力学性能改善

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