Abstract
A novel bioactive sponge was created with a composite of type I collagen sponges or porous poly(ε-caprolactone) (PCL) scaffolds, platelet-rich plasma (PRP), BMP2-loaded nanoporous silicon enclosure (NSE) microparticles, mineralizing peptide amphiphiles (PA), and mesenchymal stem cells (MSC). Primary MSC from cortical bone (CB) tissue proved to form more and larger colony units, as well as produce more mineral matrix under osteogenic differentiation, than MSC from bone marrow (BM). Coating pre-treatments were optimized for maximum cell adhesion and mineralization, while a PRP-based gel carrier was created to efficiently deliver and retain MSC and microparticles within a porous scaffold while simultaneously promoting cell recruitment, proliferation, and angiogenesis. Components and composite sponges were evaluated for osteogenic differentiation in vitro. Osteogenic sponges were loaded with MSC, PRP, PA, and NSE and implanted subcutaneously in rats to evaluate the formation of bone tissue and angiogenesis in vivo. It was found that the combination of a collagen sponge with CB MSC, PRP, PA, and the BMP2-releasing NSE formed the most bone and was most vascularized by four weeks compared to analogous composites featuring BM MSC or PCL or lacking PRP, PA, and NSE. This study indicates that CB MSC should be considered as an alternative to marrow as a source of stem cells, while the PRP-PA cell and microparticle delivery system may be utilized for diverse tissue engineering applications.
Highlights
With more than one million non-union fractures treated each year in the United States and many presenting significant challenges to repair, a significant demand persists for functional and affordable synthetic systems for in vivo bone regeneration and fracture repair [1,2,3]
mesenchymal stem cells (MSC) derived from cortical bone (CB) and bone marrow (BM) skeletal compartments were prospectively isolated from male rats and placed into primary culture to assess colony forming unit-fibroblast (CFU-F) frequency
Greater than 90% loading was achieved for MSC when delivered via platelet-rich plasma (PRP)-based injectable gel, an acceptable rate for in vivo tissue engineering and translational applications
Summary
With more than one million non-union fractures treated each year in the United States and many presenting significant challenges to repair, a significant demand persists for functional and affordable synthetic systems for in vivo bone regeneration and fracture repair [1,2,3]. Tissue engineering strategies for bone repair endeavor to create alternative but functional constructs to guide new bone formation [4]. A novel and sometimes under-utilized strategy in the biomaterials field is the combination of previously successful materials to form a novel multi-functional composite to trigger the rapid formation of bone through multiple simultaneous mechanisms. We previously described benefits of varied stem cell populations, bioactive factors, and biomaterials towards the repair of critically sized bone defects [13]. We have designed a multi-composite bioactive sponge based upon a highly porous scaffold loaded with two classes of mesenchymal stem cells, mineralizing peptide amphiphiles (PA), platelet-rich plasma (PRP), and growth factor delivering nanoporous silicon enclosure (NSE) microparticles for accelerated bone regeneration
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