Evaluation of Autologously Derived Biomaterials and Stem Cells for Bone Tissue Engineering

Abstract

Despite progress, clinical translation of tissue engineering (TE) products/technologies is limited. A significant effort is underway to develop biomaterials and cells through a minimally modified process for clinical translation of TE products. Recently, bone marrow aspirate (BMA) was identified as an autologous source of cells for TE applications and is currently being tested in clinical therapies, but the isolation methods need improvement to avoid potential for contamination and increase progenitor cell yield. To address these issues, we reproducibly processed human peripheral blood (PB) and BMA to develop autologously derived biomaterials and cells. We demonstrated PB-derived biomaterial/gel cross-linking and fibrin gel formation with varied gelation times as well as biocompatibility through support of human bone marrow-derived stem cell survival and growth in vitro. Next, we established a plastic culture-free process that concentrates and increases the yield of CD146⁺/CD271⁺ early mesenchymal progenitor cells in BMA (concentrated BMA [cBMA]). cBMA exhibited increased colony formation and multipotency (including chondrogenic differentiation) in vitro compared with standard BMA. PB-derived gels encapsulated with cBMA also demonstrated increased cell proliferation and enhanced mineralization when assessed for bone TE in vitro. This strategy can potentially be developed for use in any tissue regeneration application; however, bone regeneration was used as a test bed for this study.

Impact statement

Tissue engineering (TE) is a rapidly growing field; however, clinical translation of TE products remains challenging. Autologously sourced bone marrow aspirate (BMA) and peripheral blood (PB) offer relative ease of harvesting and host compatibility and require minimal/no regulatory approvals. In this study, concentration of BMA led to the enrichment of early progenitor cells, which can potentially improve TE outcomes. Furthermore, concentrating BMA in combination with calcium-mediated, cross-linked fibrin gels derived from PB presented enhanced proliferation and osteogenic potential for a minimally modified bone TE strategy. These findings demonstrate the potential utilization of BMA in combination with PB for development of clinically translatable TE strategies for regeneration of different tissues.