Tissue engineering provides great possibilities to manage tissue damages and injuries in modern medicine. The involvement of hard biocompatible materials in tissue engineering-based therapies for the healing of soft tissue defects has impressively increased over the last few years: in this regard, different types of bioceramics were developed, examined and applied either alone or in combination with polymers to produce composites. Bioactive glasses, carbon nanostructures, and hydroxyapatite nanoparticles are among the most widely-proposed hard materials for treating a broad range of soft tissue damages, from acute and chronic skin wounds to complex injuries of nervous and cardiopulmonary systems. Although being originally developed for use in contact with bone, these substances were also shown to offer excellent key features for repair and regeneration of wounds and “delicate” structures of the body, including improved cell proliferation and differentiation, enhanced angiogenesis, and antibacterial/anti-inflammatory activities. Furthermore, when embedded in a soft matrix, these hard materials can improve the mechanical properties of the implant. They could be applied in various forms and formulations such as fine powders, granules, and micro- or nanofibers. There are some pre-clinical trials in which bioceramics are being utilized for skin wounds; however, some crucial questions should still be addressed before the extensive and safe use of bioceramics in soft tissue healing. For example, defining optimal formulations, dosages, and administration routes remain to be fixed and summarized as standard guidelines in the clinic. This review paper aims at providing a comprehensive picture of the use and potential of bioceramics in treatment, reconstruction, and preservation of soft tissues (skin, cardiovascular and pulmonary systems, peripheral nervous system, gastrointestinal tract, skeletal muscles, and ophthalmic tissues) and critically discusses their pros and cons (e.g., the risk of calcification and ectopic bone formation as well as the local and systemic toxicity) in this regard.

Statement of Significance

Soft tissues form a big part of the human body and play vital roles in maintaining both structure and function of various organs; however, optimal repair and regeneration of injured soft tissues (e.g., skin, peripheral nerve) still remain a grand challenge in biomedicine. Although polymers were extensively applied to restore the lost or injured soft tissues, the use of bioceramics has the potential to provides new opportunities which are still partially unexplored or at the very beginning. This reviews summarizes the state of the art of bioceramics in this field, highlighting the latest evolutions and the new horizons that can be opened by their use in the context of soft tissue engineering. Existing results and future challenges are discussed in order to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers of the biomaterials community.

中文翻译：

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用于“软”组织工程的“硬”陶瓷：悖论还是机遇？

组织工程学为管理现代医学中的组织损伤和损伤提供了巨大的可能性。在过去的几年中，硬的生物相容性材料在基于组织工程的软组织缺损的治疗中的参与已显着增加：在这方面，单独，或与聚合物组合开发，检查和应用了不同类型的生物陶瓷。生产复合材料。生物活性玻璃，碳纳米结构和羟基磷灰石纳米颗粒是用于治疗各种软组织损伤（从急性和慢性皮肤伤口到神经和心肺系统的复杂损伤）的最广泛提出的硬质材料。尽管最初是为与骨骼接触而开发的，这些物质还被证明具有出色的关键特性，可修复和再生伤口和“微妙的”人体结构，包括改善细胞增殖和分化，增强血管生成以及抗菌/消炎活性。此外，当嵌入软基质中时，这些硬质材料可以改善植入物的机械性能。它们可以以各种形式和配方使用，例如细粉，颗粒，微纤维或纳米纤维。在一些临床前试验中，将生物陶瓷用于皮肤伤口。然而，在软组织愈合中广泛安全地使用生物陶瓷之前，仍应解决一些关键问题。例如，定义最佳配方，剂量，和给药途径仍然是固定的，并总结为临床的标准指南。这篇综述文章旨在全面地介绍生物陶瓷在软组织（皮肤，心血管和肺系统，外周神经系统，胃肠道，骨骼肌和眼科组织）的治疗，重建和保存中的用途和潜力。讨论了它们在这方面的利弊（例如，钙化和异位骨形成的风险以及局部和全身毒性）。

重要声明

软组织构成人体的重要组成部分，在维持各种器官的结构和功能方面起着至关重要的作用。然而，受伤的软组织（例如皮肤，周围神经）的最佳修复和再生仍然是生物医学面临的巨大挑战。尽管聚合物被广泛地用于恢复丢失或受伤的软组织，但是生物陶瓷的使用有可能提供新的机会，而这些机会仍未被部分开发或一开始就被探索。这篇综述总结了该领域的生物陶瓷技术现状，重点介绍了在软组织工程领域的应用可以为它们带来的最新发展和新视野。