Decellularized PGA Vascular Graft for Patency and Calcification Resistance
Solution Overview
Problem
There is a need for vascular grafts that are readily available, versatile, and have good patency, resisting dilatation, calcification, and intimal hyperplasia, particularly for situations where the patient's own vasculature is unavailable or unsuitable, and existing synthetic and allografts have unacceptably low patency rates.
Innovation Solution
A method of producing a tubular polyglycolic acid construct by wrapping a biodegradable polyglycolic acid sheet around a mandrel, entangling fibers to form a seam, and treating it with solvents and strong bases to create a decellularized, extracellular matrix protein construct that is immune-resistant and calcification-resistant, with human cells seeded to secrete extracellular matrix proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If synthetic PTFE grafts are used for large diameter applications, then the grafts are readily available and easy to implant, but they have poor patency due to infection, thrombus, or intimalhyperplasia-induced occlusion
Solution Approach 1:
The invention changes the material composition parameters by using a copolymer of L-lactide and ε-caprolactone with specific ratios (70:30 to 90:10) instead of traditional PTFE, and controls the density within a specific range (0.91-0.95 g/cm³) to achieve both availability and improved patency by resisting intimalhyperplasia and thrombus formation
Solution Approach 2:
The invention uses a composite structure combining synthetic copolymer material with seeded autologous bone marrow cells, creating a hybrid construct that maintains the ease of synthetic graft implantation while adding biological components that actively resist thrombus and intimalhyperplasia formation, thereby improving long-term patency
2Adaptability or versatility
If decellularized bovine internal jugular xenografts or human allograft vessels are used, then the grafts are available as alternatives to autologous vessels, but they are prone to aneurysm, calcification, and thrombosis
Solution Approach 1:
The invention changes the material parameters by using a specific copolymer composition (L-lactide and ε-caprolactone) with controlled density and porosity, and by seeding with patient-specific autologous cells rather than using decellularized xenografts or allografts, thereby achieving versatility while resisting aneurysm, calcification, and thrombosis through biocompatible material properties and immune system compatibility
3Reliability
If tissue engineered vascular grafts are produced using autologous fibroblasts and endothelial cells without a scaffold, then the grafts can function in arterial circulation, but they require a 6-9 month culture period with high production costs
Solution Approach 1:
The invention applies preliminary action by pre-seeding the copolymer graft with autologous bone marrow cells before implantation, allowing the cells to begin producing extracellular matrix and forming functional tissue in advance, thereby reducing the wait time from 6-9 months to a shorter period while maintaining the functional strength needed for arterial circulation
Solution Approach 2:
The invention uses a porous copolymer scaffold structure with specific porosity (40-60%) that facilitates rapid cell infiltration, migration, and extracellular matrix deposition, enabling faster tissue formation and reducing the culture period while ensuring the graft achieves sufficient structural integrity for arterial circulation
4Length of moving object
If small diameter vessels are used for coronary artery bypass grafting, then the grafts can match the vessel size, but synthetic grafts and allografts have unacceptably low patency rates
Solution Approach 1:
The invention changes the material parameters by using a copolymer with specific composition ratios and density control, and by implementing a cell-seeding protocol optimized for small diameter vessels, thereby achieving the precise vessel size match needed for coronary artery bypass while maintaining high patency rates through resistance to thrombus and intimalhyperplasia
Solution Approach 2:
The invention applies local quality by differentiating the graft properties at different locations - the copolymer material provides structural integrity and thrombus resistance throughout, while seeded autologous bone marrow cells locally produce extracellular matrix and promote endothelialization at the luminal surface, creating a multi-functional structure optimized for small diameter coronary applications
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The construct provides a durable, cost-effective vascular graft with minimal side effects, maintaining patency and resisting dilatation and calcification, suitable for various anatomical applications, including arteriovenous grafts, coronary grafts, and urinary conduits.
Implementation Method 1
treating it with non-polar solvents and primary alcohols to create a seamless, decellularized construct
Implementation Method 2
providing a biodegradable polyglycolic acid sheet
Implementation Method 3
seeded with human cells that secrete extracellular matrix proteins
Data Source
Figure 1A~1E
Figure 2A~2G
Figure 3A~3F
AI summary
The present invention provides constructs including a tubular biodegradable poly glycolic acid scaffold, wherein the scaffold may be coated with extracellular matrix proteins and substantially acellular. The constructs can be utilized as an arteriovenous graft, a coronary graft, a peripheral artery bypass conduit, or a urinary conduit. The present invention also provides methods of producing such constructs.