Injectable polymerized high internal phase emulsions with rapid in situ curing.

Polymerized high internal phase emulsions (polyHIPEs) have been utilized in the creation of injectable scaffolds that cure in situ to fill irregular bone defects and potentially improve tissue healing. Previously, thermally initiated scaffolds required hours to cure, which diminished the potential for clinical translation. Here, a double-barrel syringe system for fabricating redox-initiated polyHIPEs with dramatically shortened cure times upon injection was demonstrated with three methacrylated macromers. The polyHIPE cure time, compressive properties, and pore architecture were investigated with respect to redox initiator chemistry and concentration. Increased concentrations of redox initiators reduced cure times from hours to minutes and increased the compressive modulus and strength without compromising the pore architecture. Additionally, storage of the uncured emulsion at reduced temperatures for 6 months was shown to have minimal effects on the resulting graft properties. These studies indicate that the uncured emulsions can be stored in the clinic until they are needed and then rapidly cured after injection to rigid, high-porosity scaffolds. In summary, we have improved upon current methods of generating injectable polyHIPE grafts to meet translational design goals of long storage times and rapid curing (<15 min) without sacrificing porosity or mechanical properties.

Solvent-free fabrication of polyHIPE microspheres for controlled release of growth factors.

The growth factor bone morphogenetic protein 2 (BMP-2) is utilized in surgical procedures to improve bone regeneration; however, current treatments deliver BMP-2 at amounts greater than 100,000 fold of physiological levels, which increases treatment costs and risk of side effects. Drug-eluting microcarriers developed to improve these therapies have faced significant commercialization challenges including particle size distributions, solvent removal, low encapsulation efficiency, and bioactivity loss. In this study, a solvent-free method is presented for fabrication of uniform polyHIPE microspheres for controlled growth factor release. Emulsion templating principles and fluid dynamics were used to fabricate uniform particles with tunable particle size (200-800 µm) and pore size (10-30 µm). The ability to independently tune particle and pore size is expected to provide excellent control of release kinetics. Overall, this solvent-free method for making porous microspheres displays strong promise for the controlled release of BMP-2 and other growth factors.

Injectable PolyMIPE Scaffolds for Soft Tissue Regeneration.

Injury caused by trauma, burns, surgery, or disease often results in soft tissue loss leading to impaired function and permanent disfiguration. Tissue engineering aims to overcome the lack of viable donor tissue by fabricating synthetic scaffolds with the requisite properties and bioactive cues to regenerate these tissues. Biomaterial scaffolds designed to match soft tissue modulus and strength should also retain the elastomeric and fatigue-resistant properties of the tissue. Of particular design importance is the interconnected porous structure of the scaffold needed to support tissue growth by facilitating mass transport. Adequate mass transport is especially true for newly implanted scaffolds that lack vasculature to provide nutrient flux. Common scaffold fabrication strategies often utilize toxic solvents and high temperatures or pressures to achieve the desired porosity. In this study, a polymerized medium internal phase emulsion (polyMIPE) is used to generate an injectable graft that cures to a porous foam at body temperature without toxic solvents. These poly(ester urethane urea) scaffolds possess elastomeric properties with tunable compressive moduli (20-200 kPa) and strengths (4-60 kPa) as well as high recovery after the first conditioning cycle (97-99%). The resultant pore architecture was highly interconnected with large voids (0.5-2 mm) from carbon dioxide generation surrounded by water-templated pores (50-300 µm). The ability to modulate both scaffold pore architecture and mechanical properties by altering emulsion chemistry was demonstrated. Permeability and form factor were experimentally measured to determine the effects of polyMIPE composition on pore interconnectivity. Finally, initial human mesenchymal stem cell (hMSC) cytocompatibility testing supported the use of these candidate scaffolds in regenerative applications. Overall, these injectable polyMIPE foams show strong promise as a biomaterial scaffold for soft tissue repair.

Achieving interconnected pore architecture in injectable PolyHIPEs for bone tissue engineering.

Template polymerization of a high internal phase emulsion (polyHIPE) is a relatively new method to produce tunable high-porosity scaffolds for tissue regeneration. This study focuses on the development of biodegradable injectable polyHIPEs with interconnected porosity that have the potential to fill bone defects and enhance healing. Our laboratory previously fabricated biodegradable polyHIPEs that cure in situ upon injection; however, these scaffolds possessed a closed-pore morphology, which could limit bone ingrowth. To address this issue, HIPEs were fabricated with a radical initiator dissolved in the organic phase rather than the aqueous phase of the emulsion. Organic-phase initiation resulted in macromer densification forces that facilitated pore opening during cure. Compressive modulus and strength of the polyHIPEs were found to increase over 2 weeks to 43±12 MPa and 3±0.2 MPa, respectively, properties comparable to cancellous bone. The viscosity of the HIPE before cure (11.0±2.3 Pa·s) allowed for injection and filling of the bone defect, retention at the defect site during cure under water, and microscale integration of the graft with the bone. Precuring the materials before injection allowed for tuning of the work and set times. Furthermore, storage of the HIPEs before cure for 1 week at 4°C had a negligible effect on pore architecture after injection and cure. These findings indicate the potential of these emulsions to be stored at reduced temperatures and thawed in the surgical suite before injection. Overall, this work highlights the potential of interconnected propylene fumarate dimethacrylate polyHIPEs as injectable scaffolds for bone tissue engineering.

Injectable polyHIPEs as high-porosity bone grafts.

Polymerization of high internal phase emulsions (polyHIPEs) is a relatively new method for the production of high-porosity scaffolds. The tunable architecture of these polyHIPE foams makes them attractive candidates for tissue engineered bone grafts. Previously studied polyHIPE systems require either toxic diluents or high cure temperatures which prohibit their use as an injectable bone graft. In contrast, we have developed an injectable polyHIPE that cures at physiological temperatures to a rigid, high-porosity foam. First, a biodegradable macromer, propylene fumarate dimethacrylate (PFDMA), was synthesized that has appropriate viscosity and hydrophobicity for emulsification. The process of surfactant selection is detailed with particular focus on the key structural features of both polymer (logP values, hydrogen bond acceptor sites) and surfactant (HLB values, hydrogen bond donor sites) that enable stable HIPE formation. Incubation of HIPEs at 37 °C was used to initiate radical cross-linking of the unsaturated double bond of the methacrylate groups to polymerize the continuous phase and lock in the emulsion geometry. The resulting polyHIPEs exhibited ~75% porosity, pore sizes ranging from 4 to 29 µm, and an average compressive modulus and strength of 33 and 5 MPa, respectively. These findings highlight the great potential of these scaffolds as injectable, tissue engineered bone grafts.

Treatment of pancreatic pseudoaneurysm with percutaneous transabdominal thrombin injection.

Severe acute pancreatitis is associated with significant morbidity and mortality. Although rare, pancreatic pseudoaneurysm is a serious and often fatal complication of acute pancreatitis. This case report describes an alcoholic male patient with a psuedoaneurysm that was successfully treated with percutaneous transabdominal thrombin injection.