Tissue engineering scaffolds require a controlled pore size and structure to host tissue formation. Supercritical carbon dioxide (scCO 2 ) processing may be used to form foamed scaffolds in which the escape of CO 2 from a plasticized polymer melt generates gas bubbles that shape the developing pores. The process of forming these scaffolds involves a simultaneous change in phase in the CO 2 and the polymer, resulting in rapid expansion of a surface area and changes in polymer rheological properties. Hence, the process is difficult to control with respect to the desired final pore size and structure. In this paper, we describe a detailed study of the effect of polymer chemical composition, molecular weight and processing parameters on final scaffold characteristics. The study focuses on poly(DL-lactic acid) (P DL LA) and poly(DL-lactic acid-coglycolic acid) (PLGA) as polymer classes with potential application as controlled release scaffolds for growth factor delivery. Processing parameters under investigation were temperature (from 5 to 55 o C) and pressure (from 60 to 230 bar). A series of amorphous P DL LA and PLGA polymers with various molecular weights (from 13 KD to 96 KD) and/or chemical compositions (the mole percentage of glycolic acid in the polymers was 0, 15, 25, 35 and 50 respectively) were employed. The resulting scaffolds were characterised by optical microscopy, scanning electron microscopy (SEM), and micro X-ray computed tomography (µCT). This is the first detailed study on using these series polymers for scaffold formation by supercritical technique. This study has demonstrated that the pore size and structure of the supercritical P DL LA and PLGA scaffolds can be tailored by careful control of processing conditions. Key Words: poly(DL-lactic acid) (P DL LA), poly(lactic acidco-glycolic acid) (PLGA), supercritical carbon dioxide (scCO 2 ), plasticization, foaming, scaffolds *Address for correspondence: Steven M. Howdle School of Chemistry The University of Nottingham University Park Nottingham, NG 7 2RD, UK Email: steve.howdle@nottingham.ac.uk IntroductionIn tissue engineering, a porous scaffold is required to act as a template and guide for cell proliferation, differentiation and tissue growth. Scaffolds may also act as controlled release devices that deliver growth factors with rates matching the physiological need of the regenerating tissue (Langer, 1998). Poly(lactic acid) (PLA) and associated poly(lactic acid-co-glycolic acid) (PLGA) copolymers are commonly used biodegradable polymers for fabricating tissue engineering porous scaffolds. PLGA copolymers with various polymer compositions (the ratio of lactic acid and glycolic acid content in the polymer) degrade at different rates. Therefore, it is of great interest using PLGA copolymers to make scaffolds for various applications. These polymers degrade in vivo and eventually disappear at a desired rate while the native tissues grow and the degradation residues are discharged through rental filtration. Moreover, the release of encapsula...

Controlling receptor-mediated interactions between cells and template surfaces is a central principle in many tissue engineering procedures (1-3). Biomaterial surfaces engineered to present cell adhesion ligands undergo integrin-mediated molecular interactions with cells (1, 4, 5), stimulating cell spreading, and differentiation (6-8). This provides a mechanism for mimicking natural cell-to-matrix interactions. Further sophistication in the control of cell interactions can be achieved by fabricating surfaces on which the spatial distribution of ligands is restricted to micron-scale pattern features (9-14). Patterning technology promises to facilitate spatially controlled tissue engineering with applications in the regeneration of highly organized tissues. These new applications require the formation of ligand patterns on biocompatible and biodegradable templates, which control tissue regeneration processes, before removal by metabolism. We have developed a method of generating micron-scale patterns of any biotinylated ligand on the surface of a biodegradable block copolymer, polylactide-poly(ethylene glycol). The technique achieves control of biomolecule deposition with nanometer precision. Spatial control over cell development has been observed when using these templates to culture bovine aortic endothelial cells and PC12 nerve cells. Furthermore, neurite extension on the biodegradable polymer surface is directed by pattern features composed of peptides containing the IKVAV sequence (15, 16), suggesting that directional control over nerve regeneration on biodegradable biomaterials can be achieved.

Significant progress has been made during the past decade towards the clinical adoption of cell-based therapeutics. However, existing cell-delivery approaches have shown limited success, with numerous studies showing fewer than 5% of injected cells persisting at the site of injection within days of transplantation. Although consideration is being increasingly given to clinical trial design, little emphasis has been given to tools and protocols used to administer cells. The different behaviours of various cell types, dosing accuracy, precise delivery, and cell retention and viability post-injection are some of the obstacles facing clinical translation. For efficient injectable cell transplantation, accurate characterisation of cellular health post-injection and the development of standardised administration protocols are required. This review provides an overview of the challenges facing effective delivery of cell therapies, examines key studies that have been carried out to investigate injectable cell delivery, and outlines opportunities for translating these findings into more effective cell-therapy interventions.

The erosion behavior of blends of biodegradable polymers is determined by the chemical composition and the molecular organization of the surface of the material. Providing a comprehensive characterization of polymer blend surfaces requires a multi-instrumental approach, as no individual surface analysis technique can ascertain both the chemical and morphological nature of surfaces. In this study we have characterized the surfaces of immiscible and miscible blends of the biodegradable polymers poly(sebacic anhydride) (PSA) and poly(DL-lactic acid) (PLA) using the surface techniques of static secondary ion mass spectrometry (SSIMS), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). SSIMS and XPS have recorded the surface enrichment of all of the blends with the PLA component. For the immiscible blends, differential charging within the XPS spectra also provides evidence of phase separation. AFM data have contrasted the surface morphologies of the immiscible and miscible blends, and the use of in situ AFM techniques has enabled the effect of blend morphology on surface erosion to be visualized. For the immiscible systems, clear phase separation morphologies can be observed and at certain blend compositions the rapid loss of the PSA from the films results in the exposure of the PLA morphology. However, as the PLA content is increased, the surface enrichment effect results in the degradation behavior of the blend being dominated by the slow degrading PLA surface layer. For the miscible systems, the in situ AFM studies visualized a disintegration of the whole blend film without the exposure of a PLA morphology, indicating that the hydrolysis of the PSA component rendered the whole film unstable. The use of SIMS, XPS, and AFM, while highlighting the complexity of polymer blend surfaces, can provide a rapid analysis of the physicochemical phenomena underlying the organization of these systems and therefore should facilitate the application of such systems as biomaterials.

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