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



        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.