Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a complex phenotype characterized chief ly by abnormalities in fibroblasts, connective tissues, and blood vessels. Consideration of this phenotype suggested to us that the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null mice. To investigate the participation of TSP2 in the FBR, polydimethylsiloxane (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control mice. Growth of TSP2-null and control skin fibroblasts in vitro also was evaluated on both types of disks. Normal fibroblasts grew as a monolayer on both surfaces, but attachment of the cells to ox-PDMS was weak and sensitive to movement. TSP2-null fibroblasts grew as aggregates on both surfaces, and their attachment was further compromised on ox-PDMS. After a 4-week implantation period, both types of PDMS elicited a similar FBR with a collagenous capsule in both TSP2-null and control mice. However, strikingly, the collagenous capsule that formed in TSP2-null mice was highly vascularized and thicker than that formed in normal mice. In addition, abnormally shaped collagen fibers were observed in capsules from mutant mice. These observations indicate that the presence or absence of an extracellular matrix component, TSP2, can inf luence the nature of the FBR, in particular its vascularity. The expression of TSP2 therefore could represent a molecular target for local inhibitory measures when vascularization of the tissue surrounding an implanted device is desired.

This paper discusses the optimization of the solvent evaporation process to produce double-walled (DW) microspheres in a single-step. Five process variables were studied: polymer solution concentration, polymer weight ratio, polymer solution volume ratios, encapsulation temperature, and air flow rate across the top of the encapsulation vessel. The effects of these variables on the process efficiency (defined here as the percentage of microspheres with a DW configuration compared to the total number of microspheres) were examined. Total polymer concentrations of less than 20% (w/v) produced microspheres with high efficiency, with phase separation consistent across all size fractions in each batch. Changing the volume ratio of the two polymer solutions had no significant effect on the process efficiency. The weight ratio of the polymers greatly influenced the process efficiency, resulting in a low 63% efficiency for the 1:3 Poly-L-lactide (PLLA): Poly(carboxyphenoxypropane-co-sebacic)anhydride 20:80 (P(CPP:SA 20:80)) weight ratio and 0% for the 3:1 weight ratio. The 1:3 weight ratio also caused the polymers to reverse their orientation, although the efficiency for this switch was still relatively low. The temperature of the non-solvent bath affected the efficiency of certain pairs of polymers, but not all. The PLLA/Poly(lactide-co-glycolide) 50:50 (PLGA) pair was most sensitive to temperature, due to the chemical similarity of the two polymers which narrowed the range of acceptable conditions for encapsulation. Pairs of polymers which phase separated readily (e.g. polystyrene and PLLA) were the least sensitive to temperature changes. Process yield and size distribution show no clear trends with respect to air flow rate across the top of the reaction vessel. The efficiency of the process to produce DW microspheres increased and the process time decreased with increasing air flow across the surface of the encapsulation vessel.

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