Blocking of Matrix metalloproteinases-13 Responsive Peptide in Poly(urethane Urea) for Potential Cartilage Tissue Engineering Applications

Gang Wu, Huan Wang, Jiangwei Xiao, Lilu Wang, Yu Ke, Liming Fang, Chunlin Deng, Hua Liao

J Biomater Appl. 2018 Mar;32(8):999-1010.

PMID: 29359624

Abstract:

The matching of scaffold degradation rate with neotissue growth is required for tissue engineering applications. Timely provision of proper spaces especially for cartilage tissue engineering plays a pivotal role in chondrocyte cluster formation. In this study, poly(urethane urea) was synthesized using conventional two-stage method by extending the isocyanate group terminated prepolymers with different amounts of GPLGLWARK peptide, which responses the degrading induced by matrix metalloproteinase 13, the main proteinase for cartilage matrix degradation. The Fourier transform infrared spectrometer with the attenuated total reflection and 1H nuclear magnetic resonance spectra revealed that the peptides were introduced to poly(urethane urea) according to the characteristic absorption bands of the peptide and the newly formed urea bonds. The ultraviolet-visible spectroscopy spectra showed that the weight percentages of the peptide in the three poly(urethane urea) were 25%, 32%, and 35%. Atomic force microscopy images revealed that phase separation occurred in all poly(urethane urea) samples and became increasingly apparent with increasing amount of peptides introduced. Mechanical tests showed that the poly(urethane urea) strength increased with increasing amount of peptides in poly(urethane urea). Poly(urethane urea) proteolysis in matrix metalloproteinase 13 solution was more rapid than hydrolysis in aqueous buffer, and proteolysis rate was dependent on the amount of peptides in poly(urethane urea). Cell proliferation on the material surface in vitro displayed nontoxicity for all synthesized poly(urethane urea). In vivo subcutaneous implantation evaluation revealed the presence of local foreign body reactions triggered by poly(urethane urea) but was not due to peptide in poly(urethane urea). Moreover, the synthesized poly(urethane urea) with significant phase separation did not degrade under the matrix metalloproteinase 13 free subcutaneous environment, but poly(urethane urea) with minimal phase separation was degraded by attacking of the enzymes adsorbed on the hydrophobic surface through non-specific adsorption.