EVALUATION OF DIFFERENT CHEMICAL METHODS FOR CROSS-LINKING COLLAGEN GEL, FILMS AND SPONGES

Collagen-based films and sponges are widely used as biomaterials. The rate of their biodegradation can be reduced by treating them with diff erent cross-linking agents. The efficiency of different reticulation p rocedures on thermal stability (measured by differential scanning calo rimetry) and susceptibility to bacterial collagenase digestion of the final material (films or sponges) is compared. The chemical agents use d on collagen gels or directly on collagen sponges and films were glut araldehyde (GTA), hexamethylene diisocyanate (HMDC), cya nam ide, 1-et hyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and the two acyl azi de methods (with hydrazine or diphenylphosphorylazide (DPPA)) develope d in the authors' laboratory. Under these experimental conditions, col lagen stabilization by the different agents increased in the following order: cyanamide < EDC < HMDC < hydrazine < DPPA < GTA. Sponges with the highest thermal stability were obtained by treating collagen gel w ith 0.5% GTA for 1 h at pH 5.5 (initial T-d = 75.8 degrees C; after 3 months, T-d = 75.6 degrees C). Direct treatment of collagen films with DPPA gave similar thermal stability (T-d = 72.6 degrees C) and collag enase resistance when compared with treatment with 0.6% GTA for 96 h ( T-d = 74.6 degrees C). It is demonstrated that collagen sponges and fi lms can be prepared with a wide range of thermal stability (49-75.8 de grees C) and collagenase digestion resistance (10-100%). Recent biocom patibility studies show, however, that DPPA and EDC are the best choic es for preparing cross-linked collagen sponges and films.