2022, Vol. 26 ›› Issue (22): 3460-3466

Fabrication and safety evaluation of collagen sponge

Liu Chaoyuan, Gao Tianfang, Huang Wei   

Abstract: BACKGROUND: Collagen could be extracted from the animal, and the collagen sponge could be fabricated by vacuum freeze-drying technology, which is used in clinical hemostasis. Besides, it would be degraded in vivo. However, there are some concerns about collagen biomaterials, owing to the potential risk of carrying viruses and immune rejection. The biological safety of collagen hemostatic sponge was achieved by removing the terminated peptide and inactivating the virus.
OBJECTIVE: To investigate the immunogenicity and the validity of virus inactivation of collagen hemostatic sponge in commercial process.
METHODS: The collagen was extracted from bovine tendons through acid-enzymatic hydrolysis. After the vacuum freeze-drying technology, the porous collagen hemostatic sponge was prepared. The immunogenicity was investigated by insert 1 or 4 pieces of collagen sponge in Wistar rats subcutaneously. The physical sign, blood routine examination, T lymphocyte proliferation, and immunoglobulin content were examined at 1, 4, 8 and 12 weeks. Pseudorabies virus, vesicular stomatitis virus, porcine parvovirus and porcine encephalomyocarditis virus were chose as indicator virus to investigate the validity of virus   inactivation by three batches of crushed bovine tendons.
RESULTS AND CONCLUSION: (1) The collagen sponge was extracted and fabricated by freeze-drying technology in clean workshop in commercial process. The irradiation sterilization was conducted after the whole process of packaging of the collagen sponge. (2) After inserting 1 or 4 pieces of collagen sponge, the physiological signs, routine blood tests, NK cell killing activity, T lymphocyte proliferation, and immunoglobulin content of the rats were found to be normal. (3) There was no detectable virus, which could reduce the titer of these four kinds of indicator virus by more than four logs, after the acid-enzymatic process of collagen sponge. In addition, sensitive cells inoculation and blind cultivation for three generations were performed on the virus titer samples that could not be detected, and the results showed no cytopathic effect. (4) Immunogenicity and virus inactivation test results showed that the prepared collagen hemostatic sponge had good biological safety which could be used in clinical hemostasis.
Key words: collagen, sponge, hemostatic materials, terminated peptide, immunogenicity, freeze-drying, acid-enzymatic hydrolysis, virus inactivation