Compositions and Methods to Promote Endothelialization of Cardiovascular Implants

Background:

A major challenge to the clinical utilization and success of off-the-shelf vascular grafts (e.g. decellularized, devitalized and non-biologic/polymeric grafts) is endothelialization of the lumen in order to prevent thrombosis and occlusion.  Efforts to address this through the immobilization of growth factors, synthetic peptides and various proteins have typically resulted in incomplete endothelialization, especially in the center of the grafts.

Technology Overview:

This invention provides a series of fusion proteins that can be immobilized on modified surfaces of implantable devices and serve to recruit and bind monocytes, which, when bound, promote endothelialization.  These fusion proteins, when immobilized, have been shown to bind monocytes under static and flow conditions.  When these proteins were immobilized on the luminal surface of vascular grafts, specifically an acellular tissue engineered vessel, the grafts remained patent.  Because these studies also revealed that monocytes recruited to the adventitial side of the grafts appeared to result in the presence of smooth muscle cells, they may promote tissue regeneration more generally.

Advantages:

• Maintains autologous status of implants by recruiting patient's own cells
• Improves biocompatibility

Applications:

• Vascular grafts
• Heart valves
• Stents

Intellectual Property Summary:

PCT Patent Application PCT/US2023/069071 filed June 26, 2023

Stage of Development:

In vivo demonstration

Licensing Status:

Available for licensing or collaboration.

Publication Links:

• Adv. Health Mat advanced online publication
• Nat Commun. 2020; 11: 1622 (related reference)
• FASEB J. 2019 Apr; 33(4): 5089-5100 (related reference)
• J Appl Biomat & Funct Mat. 2022; 20 (general background)