Blocking of matrix metalloproteinases-13 responsive peptide in poly(urethane urea) for potential cartilage tissue engineering applications

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.

Rational design of biodegradable thermoplastic polyurethanes for tissue repair

“…Incorporation of peptides into a PU backbone can endow the PU with improved biocompatibility and biodegradability, and create a specific biological function, such as enzyme liability or enhanced cell attachment [ 67 , [139] , [140] , [141] , [142] , [143] , [144] ]. A YIGSR peptide as a chain extender was introduced into a PU backbone to enhance the endothelialization of the PU as a small-diameter vascular graft [ 139 ].…”

Physiologically Responsive Polyurethanes for Tissue Repair and Regeneration

“…[ 90 ] Similarly, Wu et al synthesized PUUs with varying ratios of GPLGLWARK peptide structures as sites for MMP 13 (the main protease for cartilage matrix degradation). [ 91 ] The strength of the polyurea increases with the proportion of peptides in the molecular chain due to hydrogen bonding. The synthetic enzyme‐responsive PUUs were hydrolyzed faster in an MMP‐13 solution than in an aqueous buffer, and the rate of hydrolysis was dependent on the ratio of peptides in the backbone.…”

“…The catalysis of substrates by enzymes can lead to changes in supramolecular structure, swelling/collapse of gels, or degradation. [128] At present, different types of polyurethanes in response to matrix metalloproteinase (MMP), [89][90][91]129] trypsin, [92] urease, [93] and esterase [94] have been developed.…”