Severe bone loss resulting from trauma, disease, or infection affects thousands of people each year. Currently, the gold standard of care for bone defects is autologous or allogenic bone grafting, in which an explanted piece of bone is placed to fill the bone defect. However, bone grafting suffers from a number of limitations, included lack of donor bone, limited success, and high complication rates that often results in the need for revision surgeries. A promising alternative to bone grafting is the delivery of potent regenerative proteins, known as morphogens, to stimulate the body’s own mechanisms of bone repair. Current therapies involve the administration of extremely high doses of a single growth factor and can result inadequate bone formation and excessive inflammation. Consequently, the delivery of a complex mixture of potent morphogens to bone injury sites may provide improved bone regeneration.
Pluripotent stem cells (PSCs) secrete a complex cadre of potent morphogens that can promote functional tissue regeneration. Therefore, we are currently developing two technologies to deliver the PSC-derived morphogens for bone regeneration. The first platform is PSC-derived-matrix (PDM) developed from decellularized PSC aggregates. Osteoinductive morphogens involved in the bone regeneration process can be produced by differentiated PSC aggregates and retained within the PSC matrix after the decellularization process. Previously, we have demonstrated the osteoinductivity of differentiated PDM through the formation of significant amounts of new bone within in vivo implantation sites. The second platform we are developing is glycosaminoglycan (GAG)-based microparticles capable of capturing and concentrating complex mixtures of PSC-derived morphogens. Multiple soluble morphogens secreted by PSCs can bind strongly to these GAG-based particles and be delivered in a concentrated format. Additionally, these morphgens can be released in vivo in a controlled gradual manner, ensuring that bone formation occurs within the site of interest. Together, these two delivery platforms may address the limitations associated with the current morphogen delivery strategies and improve bone regeneration.