Maisani Mathieu, Pezzoli Daniele, Chassande Olivier, Mantovani Diego
Laboratory for Biomaterials & Bioengineering (CRC-I), Department Min-Met-Materials Engineering & Research Center CHU de Québec, Laval University, Québec City, QC, Canada.
Laboratoire BioTis, Inserm U1026, Université de Bordeaux, Bordeaux, France.
J Tissue Eng. 2017 Jun 8;8:2041731417712073. doi: 10.1177/2041731417712073. eCollection 2017 Jan-Dec.
Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.
组织工程是自体移植或异体移植用于大骨缺损再生的一种有前景的替代方法。具有不同复杂程度的无细胞生物材料可用于多种治疗指征，以刺激宿主组织进行骨修复。然而，当受损组织中没有骨祖细胞时，必须提供具有成骨细胞分化潜能的外源性细胞。这些细胞应具有在缺损部位定植并参与新骨组织构建的能力。为实现这一目标，细胞必须存活、留在缺损部位、最终增殖并分化为成熟的成骨细胞。这些植入细胞的一个关键问题是要获得氧气和营养物质的供应：植入后血管网络的暂时缺失是细胞在植入部位存活的一个主要挑战，可以采用不同的策略来促进细胞在低氧和营养供应条件下的存活，并促进缺损区域的快速血管化。这些策略包括使用设计用于为细胞在体外和体内存活、增殖和分化创造合适微环境的支架。水凝胶是一类多样的材料，可轻松实现细胞化，并提供有效、微创的方法来填充骨缺损并促进骨组织再生。此外，通过调整其组成和加工工艺，可以获得具有适当化学、生物学和机械性能的生物相容性系统。然而，只有支架和细胞的良好组合，可能还需要结合生长因子，才能在骨再生中取得成功。本综述介绍了用于设计基于细胞化水凝胶的骨再生系统的策略，确定了水凝胶内创建的许多不同微环境的关键参数。
