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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 dimethacrylate-based injectable polyHIPEs to increase cellular interactions and direct specific behavior without compromising scaffold architecture and resulting properties for various tissue engineering applications.

SUBMITTER: Robinson JL

PROVIDER: S-EPMC4800270 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Osteoinductive PolyHIPE Foams as Injectable Bone Grafts.

Robinson Jennifer L JL McEnery Madison A P MA Pearce Hannah H Whitely Michael E ME Munoz-Pinto Dany J DJ Hahn Mariah S MS Li Huinan H Sears Nicholas A NA Cosgriff-Hernandez Elizabeth E

Tissue engineering. Part A 20160224 5-6

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 po ...[more]

PMID: 26739120

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Project description:Delivery of osteoinductive factors such as bone morphogenetic protein 2 (BMP-2) has emerged as a prominent strategy to improve regeneration in bone grafting procedures. However, it remains challenging to identify a carrier that provides the requisite loading efficiency and release kinetics without compromising the mechanical properties of the bone graft. Previously, we reported on porous, polymerized high internal phase emulsion (polyHIPE) microspheres fabricated using controlled fluidics. Uniquely, this solvent-free method provides advantages over current microsphere fabrication strategies including in-line loading of growth factors to improve loading efficiency. In the current study, we utilized this platform to fabricate protein-loaded microspheres and investigated the effect of particle size (?400 vs ?800??m) and pore size (?15 vs 30??m) on release profiles. Although there was no significant effect of these variables on the substantial burst release profile of the microspheres, the incorporation of the protein-loaded microspheres within the injectable polyHIPE resulted in a sustained release of protein from the bulk scaffold over a two-week period with minimal burst release. Bioactivity retention of encapsulated BMP-2 was confirmed first using a genetically-modified osteoblast reporter cell line. A functional assay with human mesenchymal stem cells established that the BMP-2 release from microspheres induced osteogenic differentiation. Finally, microsphere incorporation had minimal effect on the cure and compressive properties of an injectable polyHIPE bone graft. Overall, this work demonstrates that these microsphere-polyHIPE composites have strong potential to enhance bone regeneration through controlled release of BMP-2 and other growth factors. STATEMENT OF SIGNIFICANCE: This manuscript describes a method for solvent-free fabrication of porous microspheres from high internal phase emulsions using a controlled fluids setup. The principles of emulsion templating and fluid dynamics provide exceptional control of particle size and pore architecture. In addition to the advantage of solvent-free fabrication, this method provides in-line loading of protein directly into the pores of the microspheres with high loading efficiencies. The incorporation of the protein-loaded microspheres within an injectable polyHIPE scaffold resulted in a sustained release of protein over a two-week period with minimal burst release. Retention of BMP-2 bioactivity and incorporation of microspheres with minimal effect on scaffold compressive properties highlights the potential of these new bone grafts.

Project description:Protein polymers provide a unique opportunity for tunable designs of material systems due to the genetic basis of sequence control. To address the challenge of biomineralization interfaces with protein based materials, we genetically engineered spider silks to design organic-inorganic hybrid systems. The spider silk inspired domain (SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQGT)15 served as an organic scaffold to control material stability and to allow multiple modes of processing, whereas the hydroxyapatite binding domain VTKHLNQISQSY (VTK), provided control over osteogenesis. The VTK domain was fused either to the N-, C- or both terminals of the spider silk domain to understand the effect of position on material properties and mineralization. The addition of the VTK domain to silk did not affect the physical properties of the silk recombinant constructs, but it had a critical role in the induction of biomineralization. When the VTK domain was placed on both the C- and N-termini the formation of crystalline hydroxyapatite was significantly increased. In addition, all of the recombinant proteins in film format supported the growth and proliferation of human mesenchymal stem cells (hMSCs). Importantly, the presence of the VTK domain enhanced osteoinductive properties up to 3-fold compared to the control (silk alone without VTK). Therefore, silk-VTK fusion proteins have been shown suitable for mineralization and functionalization for specific biomedical applications.Statement of significanceOrganic-inorganic interfaces are integral to biomaterial functions in many areas of repair and regeneration. Several protein polymers have been investigated for this purpose. Despite their success the limited options to fine-tune their material properties, degradation patterns and functionalize them for each specific biomedical application limits their application. Various studies have shown that the biological performance of such proteins can be improved by genetic engineering. The present study provides data relating protein design parameters and functional outcome quantified by biomineralization and human mesenchymal stem cell differentiation. As such, it helps the design of osteoinductive recombinant biomaterials for bone regeneration.

Dataset Information

Osteoinductive PolyHIPE Foams as Injectable Bone Grafts.

Publications

Osteoinductive PolyHIPE Foams as Injectable Bone Grafts.

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