Rapid Heterotrophic Ossification with Cryopreserved Poly(ethylene glycol-) Microencapsulated BMP2-Expressing MSCs

Abstract

Autologous bone grafting is the most effective treatment for long-bone nonunions, but it poses considerable risks to donors, necessitating the development of alternative therapeutics. Poly(ethylene glycol) (PEG) microencapsulation and BMP2 transgene delivery are being developed together to induce rapid bone formation. However, methods to make these treatments available for clinical applications are presently lacking. In this study we used mesenchymal stem cells (MSCs) due to their ease of harvest, replication potential, and immunomodulatory capabilities. MSCs were from sheep and pig due to their appeal as large animal models for bone nonunion. We demonstrated that cryopreservation of these microencapsulated MSCs did not affect their cell viability, adenoviral BMP2 production, or ability to initiate bone formation. Additionally, microspheres showed no appreciable damage from cryopreservation when examined with light and electron microscopy. These results validate the use of cryopreservation in preserving the viability and functionality of PEG-encapsulated BMP2-transduced MSCs.

Characterization of Molecular Transport in Ultrathin Hydrogel Coatings for Cellular Immunoprotection

“…While longer time points are critical to the ultimate application of cell transplantation, this level of initial viability is consistent with that of similar eosin photoinitiated PEGDA encapsulation systems with high long term cell viability. 9,23,24 …”

Alginate Hydrogel Microencapsulation Inhibits Devitrification and Enables Large‐Volume Low‐CPA Cell Vitrification

“…[12] However, microencapsulation of porcine and ovine mesenchymal stromal cells in polyethylene glycol (PEG) hydrogel microcapsules does not affect their survival post cryopreservation also by slow freezing. [13] Moreover, it has been reported that the DMSO concentration could be reduced to 1.5 M for vitrification in QMC (~2.5 μl sample volume) if mouse mesenchymal stem cells were microencapsulated in alginate hydrogel, which is partially attributed to the preferential vitrification of water in alginate hydrogel microcapsule compared to the water in the bulk solution outside the microcapsule during cooling. [8d] However, such vitrification study has not been performed for the more stress-sensitive embryonic stem cells (ESCs) and adult human stem cells, particularly in a large sample volume for the practical application to bank stem cells.…”

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“…Researchers led by Steven Stice (University of Georgia, Athens, Georgia) previously demonstrated how BMP‐2‐expressing MSCs encapsulated in polyethylene glycol (PEG) microspheres induced the creation of ectopic bone and regenerated critically sized bone defects in rats . To improve the clinical potential of this strategy and move toward the development of an injectable biologic therapy for large bone defect healing in humans, Andrews et al next evaluated bone regeneration using a chondroitin sulfate glycosaminoglycan scaffold for the delivery vehicle for recombinant human (rh) BMP‐2 and BMP‐2 overexpressing MSCs.…”