Original Articles Assessment of Polymer=Bioactive Glass-Composite Microporous Spheres for Tissue Regeneration Applications Hussila Keshaw, M.Sc., 1 George Georgiou, Ph.D., 2 Jonny J. Blaker, Ph.D., 1 Alastair Forbes, M.D., 3 Jonathan C. Knowles, Ph.D., 2 and Richard M. Day, Ph.D. 1,3 Conformable scaffold materials capable of rapid vascularization and tissue infiltration would be of value in the therapy of inaccessible wounds. Microporous spheres of poly(D,L-lactide-co-glycolide) (PLGA) containing bioactive glass (BG) were prepared using a thermally induced phase separation (TIPS) technique, and the bioactivity, in vitro degradation, and tissue integration of the microporous spheres were assessed. Microporous spheres containing 10% (w=w) BG stimulated a significant increase in vascular endothelial growth factor secretion from myofibroblasts consistently over a 10-day period ( p < 0.01) compared with the neat PLGA microporous spheres. The microporous spheres degraded steadily in vitro over a 16-week period, with the neat PLGA microporous spheres retaining 82% of their original weight and microporous spheres containing 10% (w=w) BG retaining 77%. Both types of microporous spheres followed a similar pattern of size reduction throughout the degradation study, resulting in a 23% and 20% reduction after 16 weeks for the neat PLGA microporous spheres and PLGA microporous spheres containing 10% (w=w) BG, respectively ( p < 0.01). After in vivo implantation into a subcutaneous wound model, the TIPS micro- porous spheres became rapidly integrated (interspherically and intraspherically) with host tissue, including vas- cularization of voids inside the microporous sphere. The unique properties of TIPS microporous spheres make them ideally suited for regenerative medicine applications where tissue augmentation is required. Introduction I n regenerative medicine, bioresorbable polymer scaf- folds are used to provide a provisional matrix to guide the growth of cells until complete replacement by host tissue is achieved. Ideally, the scaffold structure and its constituent biomaterial should create an optimal environment to inte- grate and direct tissue regeneration. Conformable scaffolds for guided tissue regeneration are advantageous for apply- ing to inaccessible tissue defects, such as undermining partial-thickness or full-thickness cutaneous wounds and gastrointestinal fistulae, due to their ability to completely fill the space and be in direct contact with host tissue surfaces, thus facilitating cell infiltration from surrounding tissue. Microspheres are ideal structures for filling inaccessible tis- sue defects because they can be efficiently packed into asymmetrical spaces. Once implanted, microspheres can act as a scaffold, with predictable interstices produced between adjacent spheres guiding tissue infiltration. As with any tis- sue engineering scaffold, microspheres should have suitable surface properties that are able to direct tissue in-growth, combined with appropriate mechanical and degradation properties. If the scaffold is resorbable it should also be eventually replaced by the host tissue. 1 Poly(D,L-lactide- co-glycolide) (PLGA) is a bioresorbable copolymer frequently used in tissue engineering applications, with mechanical and degradation properties controlled by adjusting the molecular weight and copolymer ratio. 1–3 Neovascularization is an essential component of wound healing and tissue regeneration, replacing damaged capillar- ies and reestablishing a supply of oxygen and nutrients. The porosity of a scaffold will dictate the extent of vascular infil- tration from host tissue. Targeted delivery of angiogenic agents can be desirable, especially when systemic delivery of the agent could cause damage elsewhere in the body. The introduction of angiogenic growth factors directly into chronic wounds has demonstrated a positive effect on accel- erating chronic wound healing. Examples include platelet- derived growth factor, available as a topical gel (Becaplermin, [Regranex], Janssen-Cilag Ltd, Buckinghamshire, UK) and 1 Biomaterials and Tissue Engineering Group, Burdette Institute of Gastrointestinal Nursing, Kings College London, London, United Kingdom. 2 Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, London, United Kingdom. 3 Biomaterials and Tissue Engineering Group, Centre for Gastroenterology & Nutrition, University College London, London, United Kingdom. TISSUE ENGINEERING: Part A Volume 15, Number 7, 2009 ª Mary Ann Liebert, Inc. DOI: 10.1089=ten.tea.2008.0203 1451