Soft-tissue augmentation with injectable alginate and syngeneic fibroblasts

Tissue engineering, a field that combines polymer scaffolds with isolated c ell populations to create new tissue, may be applied to soft-tissue augment ation-an area in which polymers and cell populations have been injected ind ependently. We have developed an inbred rat model in which the subcutaneous injection of a hydrogel, a form of polymer, under vacuum permits direct co mparison of different materials in terms of both histologic behavior and th eir ability to maintain the specific shape and volume of a construct. Using this model, we compared three forms of calcium alginate, a synthetic hydrogel, over an 8-week period-standard alginate that was gelled following injection into animals (alginate post-gel), standard alginate that was gel led before injection into animals (alginate pre-gel) and alginate-RGD, to w hich the cell adhesion tripeptide RGD was linked covalently (RGD post-gel). Parallel groups that included cultured syngeneic fibroblasts suspended wit hin each of these three gels were also evaluated (arginate post-gel plus ce lls, alginate pre-gel plus cells, and RGD post-gel plus cells). The study u sed 54 inbred Lewis rats (n = 9 for each of the six groups). Construct geometry was optimally maintained in the alginate post-gel group in which 58 percent of the original volume was preserved at 8 weeks and inc reased to 88 percent at 8 weeks when syngeneic fibroblasts were included wi thin the gel. Volume was not as well preserved in the RGD post-gel group (2 5 percent of original volume at 8 weeks), but again increased when syngenei c fibroblasts were included (41 percent of original volume at 8 weeks). Mai ntenance of volume was poorest in the alginate pre-gel group (31 percent of original volume at 8 weeks) and failed to be augmented by the addition of fibroblasts (19 percent of original volume at 8 weeks). Histologically, the gel remained a uniform sheet surrounded by a fibrous ca psule in the alginate post-gel groups. In the alginate pre-gel and RGD post -gel groups, there was significant ingrowth of a fibrovascular stroma into the gel with fragmentation of the construct In constructs in which syngenei c fibroblasts were included, cells were visualized throughout the gel but d id not extend processes or appear to contribute to new tissue formation. Ma terial compression testing indicated that the alginate and RGD post-gel con structs became stiffer over a 12-week period, particularly in the cell-cont aining groups. Our results suggest that calcium alginate could be a suitable agent for sof t-tissue augmentation when gelled subcutaneously following injection. The a ddition of syngeneic fibroblasts enhanced the ability of the gel to maintai n the volume of a construct; this seems to be mediated by increased gel sti ffness rather than by de novo tissue formation. Our animal model, in combin ation with material testing data, permits rigorous comparison of different materials used for soft-tissue augmentation.