Ostadi Yasamin, Khanali Javad, Tehrani Fatemeh A, Yazdanpanah Ghasem, Bahrami Soheyl, Niazi Feizollah, Niknejad Hassan
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL, USA.
Biomater Res. 2024 Sep 6;28:0071. doi: 10.34133/bmr.0071. eCollection 2024.
Along with a paradigm shift in looking at soft tissue fillers from space-filling to bioactive materials, decellularized extracellular matrix (DEM) fillers have gained more attention considering their superior bioactivity. However, the complex mechanisms that govern the interaction between host tissues and DEMs have been partially understood. This review first covers the mechanisms that determine immunogenicity, angiogenesis and vasculogenesis, and recellularization and remodeling after DEM implantation into host tissue, with a particular focus on related findings from filler materials. Accordingly, the review delves into the dual role of macrophages and their M1/M2 polarization paradigm to form both constructive and destructive immune responses to DEM implants. Moreover, the contribution of macrophages in angiogenesis has been elucidated, which includes but is not limited to the secretion of angiogenic growth factors and extracellular matrix (ECM) remodeling. The findings challenge the traditional view of immune cells as solely destructive entities in biomaterials and indicate their multifaceted roles in tissue regeneration. Furthermore, the review discusses how the compositional factors of DEMs, such as the presence of growth factors and matrikines, can influence angiogenesis, cell fate, and differentiation during the recellularization process. It is also shown that the biomechanical properties of DEMs, including tissue stiffness, modulate cell responses through mechanotransduction pathways, and the structural properties of DEMs, such as scaffold porosity, impact cell-cell and cell-ECM interactions. Finally, we pointed out the current clinical applications, the bottlenecks in the clinical translation of DEM biomaterials into soft tissue fillers, as well as the naïve research areas of the field.
随着对软组织填充剂的看法从空间填充材料向生物活性材料的范式转变，脱细胞细胞外基质（DEM）填充剂因其卓越的生物活性而受到更多关注。然而，宿主组织与DEM之间相互作用的复杂机制仅得到了部分理解。本综述首先涵盖了决定免疫原性、血管生成和血管发生以及DEM植入宿主组织后再细胞化和重塑的机制，特别关注填充材料的相关研究结果。相应地，本综述深入探讨了巨噬细胞的双重作用及其M1/M2极化范式，以形成对DEM植入物的建设性和破坏性免疫反应。此外，还阐明了巨噬细胞在血管生成中的作用，包括但不限于分泌血管生成生长因子和细胞外基质（ECM）重塑。这些发现挑战了免疫细胞在生物材料中仅起破坏作用的传统观点，并表明它们在组织再生中具有多方面的作用。此外，本综述还讨论了DEM的组成因素，如生长因子和基质分子的存在，如何在再细胞化过程中影响血管生成、细胞命运和分化。还表明，DEM的生物力学特性，包括组织硬度，通过机械转导途径调节细胞反应，而DEM的结构特性，如支架孔隙率，影响细胞-细胞和细胞-ECM相互作用。最后，我们指出了当前的临床应用、DEM生物材料转化为软组织填充剂的临床转化瓶颈以及该领域的前沿研究领域。
