Biologically Active Blood Plasma-Based Biomaterials as a New Paradigm for Tissue Repair Therapies

Abstract

Platelets contain an array of growth factors, extracellular matrix molecules, and other signaling molecules that are released into the injury site upon platelet activation, thus providing the cues needed to help initiate and orchestrate tissue repair. In an effort to harness this activity for therapeutic use, autologous concentrated platelet-rich plasma (PRP) has become a popular therapy, particularly in sports medicine, where the desired outcome is to overcome the body's limitations to tissue repair and accelerate healing. However, the effectiveness of PRP therapies remains controversial due to variable clinical outcomes. Potential sources of variability include the different types of platelet concentrators as well as the inherent variation in patient-to-patient platelet and growth factor quality and quantity. Additionally, PRP, either activated pre- or postinjection, cannot be spatially contained in an injury site and is rapidly resorbed. A further limitation to PRP is that it is not a simple, off-the-shelf solution. We have developed solid, bioactive plasma-based biomaterials (PBMs) that may address these issues. Unlike platelet concentrators, which concentrate the platelets and subsequently discard a significant volume of plasma, we utilize the entire plasma (including the platelets), which contains vital growth factors and other components that are not platelet-derived. Pooled plasma is utilized to reduce PBM lot-to-lot variability. PBMs are inexpensive to manufacture, safe, available as off-the-shelf products, formable into complex 3D shapes, and biodegradable with tunable biomechanical and degradation properties. PBM retention of growth factor activity has been demonstrated with the use of cell proliferation assays. Biocompatibility has been established both in vitro and in vivo. Further, the initial feasibility of PBMs to stimulate the repair of a bone defect was demonstrated in a mouse calvarial defect model. Overall, PBMs represent a platform technology with significant potential to be a disruptive new therapy option in a variety of clinical applications, not only in major clinical markets, but also in third world and developing countries, where the need is high, but where the cost is a barrier to treatment.