Abstract
Extracellular matrices (ECMs) have emerged as promising off-the-shelf products to induce bone regeneration, with the capacity not only to activate osteoprogenitors, but also to influence the immune response. ECMs generated starting from living cells such as mesenchymal stromal cells (MSCs) have the potential to combine advantages of native tissue-derived ECMs (e.g., physiological presentation of multiple regulatory factors) with those of synthetic ECMs (e.g., customization and reproducibility of composition). MSC-derived ECMs could be tailored by enrichment not only in osteogenic cytokines, but also in immunomodulatory factors, to skew the innate immune response toward regenerative processes. After reviewing the different immunoregulatory properties of ECM components, here we propose different approaches to engineer ECMs enriched in factors capable to regulate macrophage polarization, recruit host immune and mesenchymal cells, and stimulate the synthesis of other immunoinstructive cytokines. Finally, we offer a perspective on the possible evolution of the paradigm based on biological and chemico-physical design considerations, and the use of gene editing approaches.
Highlights
Bone disorders have a worldwide prevalence since they can be derived from multiple causes, including orthopedic trauma, cancer or congenital diseases
extracellular matrices (ECMs) could be generated from living cells, e.g., mesenchymal stromal cells (MSCs), using typical tissue engineering paradigms, and afterwards decellularized [9, 10]
Circulating PMNs are quickly recruited by this chemoattractant protein matrix to the injury site. While they might contribute to fibrin clot formation [21], their main roles involve the release of proteolytic enzymes to promote tissue remodeling, and inflammatory cytokines to recruit other myeloid cells and MSCs [15]
Summary
Extracellular matrices (ECMs) have emerged as promising off-the-shelf products to induce bone regeneration, with the capacity to activate osteoprogenitors, and to influence the immune response. ECMs generated starting from living cells such as mesenchymal stromal cells (MSCs) have the potential to combine advantages of native tissue-derived ECMs (e.g., physiological presentation of multiple regulatory factors) with those of synthetic ECMs (e.g., customization and reproducibility of composition). MSC-derived ECMs could be tailored by enrichment in osteogenic cytokines, and in immunomodulatory factors, to skew the innate immune response toward regenerative processes. After reviewing the different immunoregulatory properties of ECM components, here we propose different approaches to engineer ECMs enriched in factors capable to regulate macrophage polarization, recruit host immune and mesenchymal cells, and stimulate the synthesis of other immunoinstructive cytokines.
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