Crosslinking and functionalization of acellular patches via the self-assembly of copper@tea polyphenol nanoparticles

Abstract

Decellularization is a promising technique to produce natural scaffolds for tissue engineering applications. However, non-crosslinked natural scaffolds disfavor application in cardiovascular surgery due to poor biomechanics and rapid degradation. Herein, we proposed a green strategy to crosslink and functionalize acellular scaffolds via the self-assembly of copper@tea polyphenol nanoparticles (Cu@TP NPs), and the resultant nanocomposite acellular scaffolds were named as Cu@TP-dBPs. The crosslinking degree, biomechanics, denaturation temperature and resistance to enzymatic degradation of Cu@TP-dBPs were comparable to those of glutaraldehyde crosslinked dBPs (Glut-dBPs). Furthermore, Cu@TP-dBPs were biocompatible and had abilities to inhibit bacterial growth and promote the formation of capillary-like networks. Subcutaneous implantation models demonstrated that Cu@TP-dBPs were free of calcification and allowed for host cell infiltration at day 21. Cardiac patch graft models confirmed that Cu@TP-dBP patches showed improved ingrowth of functional blood vessels and remodeling of extracellular matrix at day 60. These results suggested that Cu@TP-dBPs not only had comparable biomechainics and biostability to Glut-dBPs, but also had several advantages over Glut-dBPs in terms of anticalcification, remodeling and integration capabilities. Particularly, they were functional patches possessing antibacterial and proangiogenic activities. These material properties and biological functions made Cu@TP-dBPs a promising functional acellular patch for cardiovascular applications.

Oxidative Coupling and Self-Assembly of Polyphenols for the Development of Novel Biomaterials

“…These functional patches possessed antibacterial and proangiogenic activities. 112 Antibody immobilization on the surface of nanoparticles to prevent recognition by antigen is an important area of research in nano-biotherapeutics. 113 Electrostatic and hydrophobic interactions are responsible for antibody binding on nanoparticles; these binding forces are usually difficult to control.…”

“…Cardiac patch graft models confirmed that Cu@TP-dBP patches demonstrated improved in-growth of functional blood vessels and extracellular matrix remodeling within 60 days. These functional patches possessed antibacterial and proangiogenic activities …”

“…Unfortunately, natural scaffolds that are not cross-linked have weak biomechanics and fast degradation and cannot be used in cardiovascular surgeries. Li et al 112 developed a cross-linked and functionalized building block by self-assembly of copper@tea polyphenol nanoparticles (Cu@TP-dBPs). The Cu@TP-dBPs were compatible and could reduce bacterial reproduction and potentiate the development of capillary-like networks.…”

Decellularized extracellular matrix-based composite scaffolds for tissue engineering and regenerative medicine

“…Li et al . [ 178 ] functionalized bovine pericardia dECM scaffold with copper@tea polyphenol self-assembly nanoparticles based on the coordination of tea polyphenol with copper ions. As expected, the scaffold maintained the antimicrobial activity of nanoparticles, which also exhibited anti-calcification, remodeling and integration properties for cardiovascular applications.…”

Exogeneous metal ions as therapeutic agents in cardiovascular disease and their delivery strategies

“…From nanoparticles and hydrogels to various types of scaffolds and patches [ 118 ], the application of innovative biomaterials in the field of therapeutic factor delivery has shed new light on the CVD therapy [ 119 , 120 ]. In order to transfer metal ions that may have therapeutic effects to the diseased regions, researchers have been introduced a variety of carriers [ 121 ].…”