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Publication Number
US-11471567-B2
Publication Date
2022-10-18
Expiration Date
Abstract
The present disclosure relates to methods of preparing personalized blood vessels, useful for transplantation with improved host compatibility and reduced susceptibility to thrombosis. Also provided are personalized blood vessels produced by the methods and use thereof in surgery.
Core Innovation
The invention provides a method of preparing a personalized blood vessel by contacting a surface of an acellular tubular scaffold with an undiluted whole blood sample from a subject in need of the personalized blood vessel. The contacting is performed for 3 days to 21 days, with extended contact of the scaffold surface with whole blood.
The disclosed approaches include contacting whole blood with anti-thrombotic agents and whole-blood factors, including heparin, dextran-40, ascorbic acid, acetylsalicylic acid, and growth factors at or above physiological levels, including FGF-2 and VEGF. In described implementations, the acellular tubular scaffold is a decellularized blood vessel and/or a bioprinted tubular scaffold.
The disclosure further includes systems and workflows that contact or perfuse the acellular tubular scaffold with blood in vitro for extended durations, including more than about 2 days, with examples extending to about 2-21 days and closed recirculation for reconditioning. Reconditioning/recellularization leads to scaffold cellular marker expression and graft characterization, including staining for endothelial markers such as CD31 and vWF and VE-cadherin, with endothelialization observed over extended timepoints.
An in vivo porcine example is described using DNA-free decellularized scaffolds and a closed-loop reconditioning period using autologous blood suspension with heparin and recombinant growth factors, along with acetylsalicylic acid and glucose maintenance. The example describes patent grafts without macroscopic thrombosis and endothelialization assessed by staining methods including H&E/DAPI and CD31 over a multi-week period.
Claims Coverage
The partial content identifies one independent claim (clm-00001). Across the dependent claims referenced in the family summary, multiple inventive features refine the whole-blood contacting composition and duration, and the scaffold cellularization effects, for a total of several inventive feature areas tied to the same core method.
Personalized blood vessel via acellular scaffold and undiluted whole blood contacting
A method comprising contacting a surface of an acellular tubular scaffold with an undiluted whole blood sample from a subject in need of the personalized blood vessel.
Extended contacting duration for scaffold preparation
The contacting is performed for 3 days to 21 days.
Heparin in undiluted whole blood at a defined concentration at the start of contacting
Having heparin present in the undiluted whole blood sample at a concentration of about 0.5 to about 150 IU/mL when contacting the acellular tubular scaffold surface at the beginning of contacting.
Ascorbic acid in undiluted whole blood at a defined concentration at the start of contacting
Contacting the acellular tubular scaffold with an undiluted whole blood sample containing ascorbic acid at the start of contact at a concentration from about 0.2 μg/mL to about 200 μg/mL.
Growth-factor-enriched whole blood at or above population average physiological levels
Using a whole blood sample that contains at least the population average physiological level of one or more specified growth factors.
Contacting duration narrowed to 3 to 14 days
Carrying out the contacting step for 3 to 14 days.
Cell population from whole blood populates the acellular tubular scaffold
Allowing a population of cells in a whole blood sample to populate an acellular tubular scaffold.
Overall, the claims coverage focuses on preparing a personalized blood vessel by contacting an acellular tubular scaffold surface with undiluted whole blood for an extended period, with dependent claims specifying anti-thrombotic agent content, growth-factor composition relative to population average physiological levels, alternative contacting duration windows, and allowing cells from whole blood to populate the scaffold.
Stated Advantages
Improved host compatibility.
Reduced thrombosis risk / absence of macroscopic thrombosis as described in the example.
Documented Applications
Implantation/transplantation use of the prepared personalized blood vessels.
Use for venous disorders, including DVT, CVI, varicose veins, and venous ulceration [procedural detail omitted for safety].
Use in a porcine in vivo example involving a decellularized scaffold reconditioned with autologous blood suspension, producing patent grafts and endothelialization assessed over time.
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