Synthetic scaffold materials are used in tissue engineering for a variety of applications, including physical supports for the creation of functional tissues, protective gels to aid in wound healing and to encapsulate cells for localized hormone-delivery therapies. In order to encourage successful tissue growth, these scaffold materials must incorporate vital growth factors that are released to control their development. A major challenge lies in the requirement for these growth factor delivery mechanisms to mimic the in-vivo release profiles of factors produced during natural tissue morphogenesis or repair. This review highlights some of the major strategies for creating scaffold constructs reported thus far, along with the approaches taken to incorporate growth factors within the materials and the benefits of combining tissue engineering and drug delivery expertise.

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We report the use of supercritical carbon dioxide (scCO 2 ) to create a diverse range of polymeric composites incorporating thermal and solvent labile guest materials such as proteins; no additional co-solvents are required; the entire process can be carried out at near ambient conditions; polymer morphology is controllable; high loadings of guest species can be achieved and the protein function is retained.

In this study we tested the use of salivary cortisol and cortisone as alternatives to serum cortisol. Salivary cortisol is often undetectable and contaminated by hydrocortisone. Salivary cortisone strongly reflects serum cortisol.

Twice-daily Chronocort approximates physiologic cortisol secretion, and was well tolerated and effective in controlling androgen excess in adults with CAH. This novel hydrocortisone formulation represents a new treatment approach for patients with CAH.

A new method of surface-selective laser sintering (SSLS) leads to the fabrication of threedimensional (3D) composite scaffolds (spatial resolution ∼200 μm) that are both bioactive and biodegradable. Moreover, the scaffolds can have very precise dimensions and intricate structure. Conventionally, in selective laser sintering (SLS), the polymer absorbs infrared (λ=10.6 μm) radiation and this leads to a volumetric absorption by the whole polymer particle. In other words, each particle of polymer is completely melted and fuses to the next in order to form the desired morphology. In our experiments we have used near-infrared (λ=0.97 μm) laser radiation, which polymer particles do not absorb at all. To initiate the sintering process a small quantity (< 0.1 wt.-%) of carbon microparticles were homogeneously distributed on the surfaces of the polymer particles. Thus, the melting process was limited to only the surfaces of each particle. The carbon microparticles are strong absorbers of laser radiation, and this opens up the technique to a range of polymers that up till now could not be processed by laser sintering. More importantly, since the laser melts only the surfaces of the particles, delicate bioactive species trapped within each particle retain their activity throughout the processing. We have demonstrated the application of this technique by the incorporation of the enzyme ribonuclease A into particles of poly(D,L-lactic) acid (PLA) and the assembly of 3D matrices at three different laser intensities, using a 0.97 μm wavelength continuous wave (CW) diode laser.Polymer composite structures, in which biologically active guest species are dispersed throughout a suitable porous polymer matrix to encourage formation of new tissue, have widespread biomedical applications as scaffolds for tissue engineering.[1,2] Conventional methods of preparing such composites normally use either organic liquid solvents (e.g., solvent casting, particulate leaching) or raised temperature (e.g., melt molding, thermally induced phase separation) to process the polymer. This often leads to solvent and thermally

The ability to deliver, over time, biologically active osteogenic growth factors by means of designed scaffolds to sites of tissue regeneration offers tremendous therapeutic opportunities in a variety of musculoskeletal diseases. The aims of this study were to generate porous biodegradable scaffolds encapsulating an osteogenic protein, bone morphogenetic protein 2 (BMP-2), and to examine the ability of the scaffolds to promote human osteoprogenitor differentiation and bone formation in vitro and in vivo. BMP-2-encapsulated poly(DL-lactic acid) (PLA) scaffolds were generated by an innovative supercritical fluid process developed for solvent-sensitive and thermolabile growth factors. BMP-2 released from encapsulated constructs promoted adhesion, migration, expansion, and differentiation of human osteoprogenitor cells on three-dimensional scaffolds. Enhanced matrix synthesis and cell differentiation on growth factor-encapsulated scaffolds was observed after culture in an ex vivo model of bone formation developed on the basis of the chick chorioallantoic membrane model. BMP-2-encapsulated polymer scaffolds showed morphologic evidence of new bone matrix and cartilage formation after subcutaneous implantation and within diffusion chambers implanted into athymic mice as assessed by X-ray analysis and immunocytochemistry. The generation of three-dimensional biomimetic structures incorporating osteoinductive factors such as BMP-2 indicates their potential for de novo bone formation that exploits cell-matrix interactions and, significantly, realistic delivery protocols for growth factors in musculoskeletal tissue engineering.

This phase 1 study demonstrates that Infacort is safe, well tolerated, of neutral taste, bioequivalent to hydrocortisone licensed for adults, and shows dose proportionality with respect to cortisol exposure. Infacort is expected to facilitate optimization of hydrocortisone dosing in neonates and children with adrenal insufficiency; however, clinical studies will be required to demonstrate efficacy in this patient age group.