Extracorporeal Wound Simulation as a Foundation for Tissue Repair and Regeneration Therapies

The idea of extracorporeally simulating a wound microenvironment ex vivo in order to obtain growth factor proteins that can then be delivered in vivo to aid wound healing is based on the premise that wound repair operates on a set of complex, yet defined physiological rules. By recapitulating this language, in the form of deliverable growth factor signaling packages, it is possible to effectively influence specific phases of the wound healing program, on demand. The ability to distinctly capture growth factors that are released from cells upon coagulation (coagulation-induced signaling phase) and growth factors that are produced by cells under hypoxia (hypoxia-induced signaling phase) is critical, and represents the most basic segregation of the multi-factorial wound healing cascade. Hypoxia-induced blood-derived secretomes, such as Hypoxia Preconditioned Plasma (HPP) and Hypoxia Preconditioned Serum (HPS), constitute such phase-specific growth factor signaling mixtures that can be obtained through Extracorporeal Wound Simulation (EWS). Novel compositions comprising adjustable concentrations of these secretomes can be added to suitable carriers, and be topically applied or injected into tissue in order to provide angiogenic support and accelerate wound healing and tissue repair. Here we present the research that has laid the foundation for this concept, and discuss how EWS can provide a new platform for developing regenerative therapies.