Decellularized Dermal Matrix Vascular Grafts for Mechanical Strength
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Solution Overview
Problem
Current engineered vascular grafts lack the mechanical strength to handle human blood pressures due to insufficient collagen production, and existing methods to increase strength either prolong manufacturing time or risk graft rejection through foreign body responses.
Innovation Solution
The use of decellularized extracellular matrix, specifically from skin dermis, as a scaffold to integrate with cells and provide a collagen network, combined with growth factors like TGF-β and ascorbic acid to enhance collagen production, results in a strong, all-natural vascular graft with improved structural support.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If growth factors like ascorbic acid and TGF-β are used to stimulate collagen production, then collagen production is promoted, but the mechanical strength remains insufficient
Solution Approach 1:
Acellular dermal matrix is introduced as an intermediary component that provides a pre-formed collagen framework. This matrix serves as a mediator between the cell culture system and the final graft structure, enabling adequate collagen production and mechanical strength without requiring extensive growth factor stimulation or prolonged culture periods
2Strength
If perfusion strength conditioning is applied for several weeks, then vascular graft strength is increased, but manufacturing time is significantly elongated
Solution Approach 1:
The acellular dermal matrix provides preliminary structural support and a pre-organized collagen architecture before cell seeding. This preliminary action eliminates the need for weeks of perfusion conditioning, as the mechanical framework is already established, allowing strength to be achieved in a fraction of the time
3Strength
If a stiff polymeric tube is integrated into the graft, then structural support is increased, but the risk of graft rejection increases due to foreign body response
Solution Approach 1:
The material composition is changed from synthetic polymers to biologic tissue (acellular dermal matrix). This parameter change maintains the necessary structural support while eliminating the foreign body response that causes rejection, as the biologic matrix is more compatible with the host tissue
4Object-affected harmful factors
If all-biological tubes are used as the basis of engineered grafts, then biocompatibility is improved, but mechanical strength is insufficient
Solution Approach 1:
The graft is constructed as a composite system combining cells, hydrogel, and acellular dermal matrix. This composite structure leverages the biocompatibility of biological components while the dense collagen network of the dermal matrix provides the necessary mechanical strength that individual biological components alone cannot achieve
Data Source
AI summary
Described herein are decellularized extracellular matrix for mechanically supporting engineered vascular grafts. Methods are provided for fabricating all-natural, non-immunogenic, strong products that do not rely on common plastic supports. Also provided are bench-top models of atherosclerosis. Embodiments provide completely inclusive models that contain all steps of atherosclerosis, including late-stage disease processes. Example models utilize tissue engineered blood vessels (TEBV); stages of atherosclerosis are induced for instance by application of oxidized low-density lipoprotein (oxLDLs) (early-stage), followed by macrophage introduction (early-stage), and induction of calcification using calcified protein particles (CPPs; late-stage). Also provided are kits useful to investigate disease processes and better patient treatment options, including new drug development.