In vivo evaluation of poly(N-isopropylacrylamide) (PNIPAM)-grafted gelatin as an in situ-formable scaffold.

We examined whether poly(N-isopropylacrylamide)-grafted gelatin (PNIPAM-gelatin) with a lower critical solution temperature of approximately 34 degrees C, which was prepared by quasi-living radical graft polymerization, can serve as an in situ-formable three-dimensional extracellular matrix or cell scaffold. A mixture of fibroblasts stained with fluorescent dye and PNIPAM-gelatin in Dulbecco's modified Eagle's medium solution was injected into the subcutaneous tissue of Wistar rats, and immediately formed a white, opaque cell-incorporated gel. Fibroblasts immediately after injection were spherical in shape and were homogeneously distributed in the gel. Fibroblasts in the gel 2 weeks after injection had spread and proliferated. One day after injection, many macrophages and neutrophiles were observed around the gel. As the implantation period proceeded, the inflammation reaction subsided. One week after injection, fibroblasts in the native tissue and macrophages migrated into the gel. From 6 to 12 weeks after injection, some degree of calcification in the solid tissue was intermittently observed. The weight of the gel 6 weeks after implantation was reduced to almost one-half of the weight of the originally injected sample. The potential usefulness of PNIPAM-gelatin as an injectable scaffold is discussed.