Osteoinductive PolyHIPE Foams as Injectable Bone Grafts

Abstract

We have recently fabricated biodegradable polyHIPEs as injectable bone grafts and characterized the mechanical properties, pore architecture, and cure rates. In this study, calcium phosphate nanoparticles and demineralized bone matrix (DBM) particles were incorporated into injectable polyHIPE foams to promote osteoblastic differentiation of mesenchymal stem cells (MSCs). Upon incorporation of each type of particle, stable monoliths were formed with compressive properties comparable to control polyHIPEs. Pore size quantification indicated a negligible effect of all particles on emulsion stability and resulting pore architecture. Alizarin red calcium staining illustrated the incorporation of calcium phosphate particles at the pore surface, while picrosirius red collagen staining illustrated collagen-rich DBM particles within the monoliths. Osteoinductive particles had a negligible effect on the compressive modulus (*30 MPa), which remained comparable to human cancellous bone values. All polyHIPE compositions promoted human MSC viability (*90%) through 2 weeks. Furthermore, gene expression analysis indicated the ability of all polyHIPE compositions to promote osteogenic differentiation through the upregulation of bone-specific markers compared to a time zero control. These findings illustrate the potential for these osteoinductive polyHIPEs to promote osteogenesis and validate future in vivo evaluation. Overall, this work demonstrates the ability to incorporate a range of bioactive components into propylene fumarate dimethacrylatebased injectable polyHIPEs to increase cellular interactions and direct specific behavior without compromising scaffold architecture and resulting properties for various tissue engineering applications.

Improved in situ seeding of 3D printed scaffolds using cell-releasing hydrogels

“…[32] In addition to confirming osteogenic potential, this study aimed to elucidate a potential mechanism behind this increased calcium deposition and assess its impact on osteoblastic differentiation. Extracellular calcium is known to play a key role in bone regeneration via direct activation of Ca-sensing receptors that result in increased osteoblast proliferation, expression of osteoinductive factors, and matrix mineralization.…”

“…We previously reported that unmodified scaffolds based on propylene fumarate dimethacrylate promoted osteoblastic differentiation under standard culture conditions, demonstrating the inherent osteoinductive character of these grafts. [32, 33] In the current study, we aimed to better understand the mechanism behind this osteoinductive character by isolating the effects of scaffold chemistry and surface area on osteoblastic differentiation. Collectively, this work aims to highlight the potential of cell-laden 3D printed scaffolds to serve as rigid cell carriers and improve the regenerative capacity of tissue engineered bone grafts.…”

Prevention of Oxygen Inhibition of PolyHIPE Radical Polymerization Using a Thiol-Based Cross-Linker

“…We previously demonstrated the ability of polyHIPE scaffolds to serve as a delivery vehicle for a multitude of osteoinductive agents and support osteogenic activity of seeded hMSCs as confirmed by early and late stage gene expression. 13 Furthermore, unmodified PFDMA scaffolds also reported osteogenic differentiation under standard culture conditions demonstrating an inherent osteoinductive character of these grafts. In this study, ALP enzyme activity was assessed as an early marker of osteoblastic differentiation of seeded hMSCs to confirm that thiol-methacrylate polyHIPEs retained this ability to support osteogenic activity.…”

The Chemistry of Porous Polymers: The Holey Grail

“…PHs have been applied as flow‐through supports, membranes, and column packing, as adsorbents‐absorbents (for removing organic and metal ion contaminants from water and for oil‐spill clean‐up), as scaffolds for tissue engineering, as containers for controlled release, and as precursors for porous inorganics and porous carbons. They have been applied as monoliths, as membranes, as beads, as injectable HIPEs for biomedical applications, and as inks for additive manufacturing …”

“…Polymerization chemistries are being developed to take advantage of monomers from renewable resources and macromolecular structural chemistries are being developed to enhance degradability. PHs that were based on renewable resource monomers such as polyphenols (e. g., tannin, tannic acid, lignin), plant oils (e. g., soybean, castor), polysaccharides (e. g., alginate, chitosan, dextrin, pectin), and lactide have recently been developed, as were PHs that were based on polymers containing degradable groups (e. g., esters) . In addition, the recent advent of reactive surfactants and/or reactive nanoparticles for HIPE stabilization has produced a significant reduction in the amounts of leachable components.…”