ABSTRACT There is an increasing need to generate novel materials for the treatment and augmentation of bone defects, affecting millions of people worldwide. Fibrillar type I collagen is the most abundant tissue matrix protein in bone, providing its key native scaffolding material. However, while in vitro reconstituted collagen hydrogels of physically entangled, nano-fibred meshes, have long served as three-dimensional cultures, their highly-hydrated nature impacts their physiological relevance. In an effort to create biomimetic collagen gels, approaches have been undertaken to generate osteoid-like environments with increased collagen concentrations, controlled fibrillar orientation, defined micro-architectures, and tailored mechanical properties. This review describes the state-of-the-art on collagen densification techniques, exploring their advantages, limitations and future perspectives for applications as bone grafts. Ultimately, by successfully mimicking the organic milieu of bone through acellular or cell-mediated mineralisation of the designed osteoid-like structure, functional collagen scaffolds with potential applications in bone tissue engineering can be realised. Abbreviations: 3D: three-dimensional; BG: bioactive glass; CFD: collagen fibrillar density; CHA: carbonated-hydroxyapatite; Col1: Type I collagen; ECM: extracellular matrix; GAE: gel aspiration-ejection; HHC: highly hydrated collagen; MSC: mesenchymal stem cell; NCPs: non-collagenous proteins; PC: plastic compression; PILP: polymer-induced liquid precursor; SBF: simulated body fluid

中文翻译：

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致密纤维状胶原基水凝胶作为功能性类骨质模拟支架

摘要 越来越需要生产用于治疗和增强骨缺损的新型材料，影响着全世界数百万人。纤维状 I 型胶原蛋白是骨骼中最丰富的组织基质蛋白，是其关键的天然支架材料。然而，虽然物理缠结的纳米纤维网的体外重组胶原水凝胶长期以来一直作为三维培养物，但它们的高度水合性质影响了它们的生理相关性。在努力创建仿生胶原凝胶的过程中，已经采取了一些方法来产生类骨质环境，该环境具有增加的胶原浓度、受控的纤维取向、明确的微结构和定制的机械性能。这篇综述描述了胶原蛋白致密化技术的最新技术，探索它们作为骨移植物的优势、局限性和未来前景。最终，通过设计的类骨质结构的无细胞或细胞介导的矿化成功模拟骨骼的有机环境，可以实现在骨组织工程中具有潜在应用的功能性胶原支架。缩写： 3D：三维；BG：生物活性玻璃；CFD：胶原纤维密度；CHA：碳酸化羟基磷灰石；Col1：I型胶原蛋白；ECM：细胞外基质；GAE：凝胶抽吸-喷射；HHC：高度水合的胶原蛋白；MSC：间充质干细胞；NCPs：非胶原蛋白；PC：塑料压缩；PILP：聚合物诱导的液体前体；SBF：模拟体液 通过设计的类骨质结构的无细胞或细胞介导的矿化成功模拟骨骼的有机环境，可以实现在骨组织工程中具有潜在应用的功能性胶原支架。缩写： 3D：三维；BG：生物活性玻璃；CFD：胶原纤维密度；CHA：碳酸化羟基磷灰石；Col1：I型胶原蛋白；ECM：细胞外基质；GAE：凝胶抽吸-喷射；HHC：高度水合的胶原蛋白；MSC：间充质干细胞；NCPs：非胶原蛋白；PC：塑料压缩；PILP：聚合物诱导的液体前体；SBF：模拟体液 通过设计的类骨质结构的无细胞或细胞介导的矿化成功模拟骨骼的有机环境，可以实现在骨组织工程中具有潜在应用的功能性胶原支架。缩写： 3D：三维；BG：生物活性玻璃；CFD：胶原纤维密度；CHA：碳酸化羟基磷灰石；Col1：I型胶原蛋白；ECM：细胞外基质；GAE：凝胶抽吸-喷射；HHC：高度水合的胶原蛋白；MSC：间充质干细胞；NCPs：非胶原蛋白；PC：塑料压缩；PILP：聚合物诱导的液体前体；SBF：模拟体液 3D：三维；BG：生物活性玻璃；CFD：胶原纤维密度；CHA：碳酸化羟基磷灰石；Col1：I型胶原蛋白；ECM：细胞外基质；GAE：凝胶抽吸-喷射；HHC：高度水合的胶原蛋白；MSC：间充质干细胞；NCPs：非胶原蛋白；PC：塑料压缩；PILP：聚合物诱导的液体前体；SBF：模拟体液 3D：三维；BG：生物活性玻璃；CFD：胶原纤维密度；CHA：碳酸化羟基磷灰石；Col1：I型胶原蛋白；ECM：细胞外基质；GAE：凝胶抽吸-喷射；HHC：高度水合的胶原蛋白；MSC：间充质干细胞；NCPs：非胶原蛋白；PC：塑料压缩；PILP：聚合物诱导的液体前体；SBF：模拟体液