Adv Healthc Mater. 2018;7(19):1-9.

        由间充质前体产生的天然细胞外基质(ECM)是由结构蛋白(主要是胶原蛋白)、蛋白聚糖和特殊的多粘附蛋白组成的复杂实体。在骨骼发育过程中，基于胶原的ECM作为矿化组织沉积的临时基质，同时也作为许多调节细胞活动(如细胞内通讯、生长和分化)的信号分子的蓄水池。为了模拟天然ECM的多功能性，我们制作了无支架单层MSC片、MSC/ECM块和球体。这些基于ECM的生物材料可以在一定程度上模拟天然的细胞环境，并显示出牙周和小骨缺损(直径约1.6毫米)再生的功效。然而，由于MSC/ECM复合物的生物力学强度和骨传导性较差，临界大小的骨缺损仍然是其面临的重大挑战。

        受自然界的启发，来自郑州大学的一个团队研发出胚胎样矿化的ECM/干细胞微球(MECS)，其中干细胞微球(CS)的自组装和自产生的ECM的矿化同时发生。均质大小的MECS呈现实心球形外观，内含干细胞，概括了膜内骨化的早期阶段。与纯CS相比，MECS具有增强的杨氏模量、细胞活力、细胞间通讯和成骨分化。此外，他们还探索了在不使用外源性支架的情况下，MECS在大鼠严重缺损中替代和修复丢失骨的能力。发现MECS可以实现良好的骨再生的结果，97.99±2.28%的缺陷区域充满了新的骨结构和血管,而CS或β-TCP仅有近一半(52.79±4.63%)或三分之一(38.09±7.79%)的缺陷区域被修复修复。研究表明，胚胎样MECS是一种新的有效的骨组织再生的骨移植替代物。

        The native extracellular matrix (ECM) produced by mesenchymal precursors is a complex entity composed of structural proteins (primarily collagen), proteoglycans, and specialized multi-adhesive proteins. During skeletal development, the collagen-based ECM serves as a temporary matrix for mineralized tissue deposition, and also acts as a reservoir for many signaling molecules modulating cell activities such as intracellular communication, growth and differentiation. To mimic the multifunctionality of native ECM, scaffold-free monolayer MSC sheets, MSC/ECM clumps and spheroids have been fabricated. These ECM-based biomaterials could mimic the native cellular environment to some extent, and show efficacy in periodontal and small bone defect (ca. 1.6 mm in diameter) regeneration. However, critical-sized bone defects remain a significant challenge for MSC/ECM complexes due to their feeble biomechanical strength and poor osteoconductivity.

        Inspired by nature, the embryonic-like mineralized ECM/stem cell microspheroids (MECS) are developed by a team from Zhengzhou University, in which self-assembly of the stem cell microspheroids (CS) and mineralization of the self-produced ECM occur simultaneously. The uniform-sized MECS exhibit a solid spherical appearance with stem cells embedded inside, recapitulating the early stage of intramembranous ossification. Compared with pure CS, MECS show enhanced Young’s modulus, cell viability, intercellular communication, and osteogenic differentiation. Additionally, the capability of MECS is explored without the use of exogenous scaffolds to substitute and repair lost bone in rat critical-sized defects. It is found that the MECS can achieve excellent bone regeneration outcomes with 97.99 ± 2.28% of the defect area filled with new bony structures and blood vessels, while nearly half or one-third of the defect area is repaired by CS (52.79 ± 4.63%) or β-tricalcium phosphate (38.09 ± 7.79%), respectively. The study demonstrates that embryonic-like MECS is a novel effective bone graft substitute for bone tissue regeneration.

孙烁