No abstract

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.

Two techniques for transferring biomaterial using a pulsed laser beam were developed: matrix-assisted pulsed laser evaporation (MAPLE) and MAPLE direct write (MDW). MAPLE is a large-area vacuum based technique suitable for coatings, i.e., antibiofouling, and MDW is a localized deposition technique capable of fast prototyping of devices, i.e., protein or tissue arrays. Both techniques have demonstrated the capability of transferring large (mol wt&gt;100 kDa) molecules in different forms, e.g., liquid and gel, and preserving their functions. They can deposit patterned films with spatial accuracy and resolution of tens of μm and layering on a variety of substrate materials and geometries. MDW can dispense volumes less than 100 pl, transfer solid tissues, fabricate a complete device, and is computed aided design/computer aided manufacturing compatible. They are noncontact techniques and can be integrated with other sterile processes. These attributes are substantiated by films and arrays of biomaterials, e.g., polymers, enzymes, proteins, eucaryotic cells, and tissue, and a dopamine sensor. These examples, the instrumentation, basic mechanisms, a comparison with other techniques, and future developments are discussed.

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.

The studies here described were carried out in connection with a program which required the characterization with respect to molecular weight of nitrocellulose fractions available only in small quantities. A diffusion method has been developed which offers the advantages of simplicity of construction and operation of the apparatus and interpretation of results. Although diffusion is less sensitive to molecular weight than viscosity, the method submitted appears to be simpler for use on a milligram scale and to afford sufficient precision for many requirements.The diffusion method reported herein differs from other diffusion methods in that the liquid medium is held fixed in position by a matrix of fine-grained filamentous material; more specifically, in these experiments the matrix was composed of a pad of filter papers. This feature effectively dampens out convection currents in the liquid medium; yet the matris is not sufficiently dense t o interfere appreciably with the diffusion process.Experimental and theoretical diffusion studies have been extensively reviewed by Longsn-orth (6) and by Killiams and Cady (8). The latter authors have given solutions of the diffusion equation for several sets of initial and/or boundary values. In principle, the diffusion constant can he calculated from an accurate knowledge of these initial and boundary values and one set of concentration, position, and time measurrmentq at some time after diffusion has been allowed to commence. In pr:icticr, : I numher of sets of measurements are made and the diffusion constant iz wported aftcr home ar-?raging process has been