Elastogenic Cues for Vascular Tissue Engineering
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Solution Overview
Problem
Current tissue engineering techniques face challenges in generating functional and structurally sound connective tissues, particularly in cardiovascular applications, due to inadequate elastin synthesis by adult vascular cells and the tendency of vascular cells to become hyper-prolific during inflammatory vascular disease, which compromises tissue homeostasis and mechanical strength.
Innovation Solution
The use of elastogenic cues such as hyaluronic acid oligomers, growth factors, and copper ions to upregulate elastin synthesis and stabilize the extracellular matrix, including specific-sized HA oligomers and polymers, and copper-containing nanostructures to enhance crosslinking and formation of insoluble elastin matrices.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If adult vascular cells are used for tissue engineering, then the cells can be obtained from native tissue sources, but elastin synthesis is innately poor and insufficient for functional tissue regeneration
Solution Approach 1:
The patent applies parameter changes by modifying the biochemical environment through addition of elastogenic cues (growth factors, cytokines, and small molecule compounds) to upregulate elastin synthesis gene expression and protein production in adult vascular cells, transforming them from poor elastin producers into functional elastin-synthesizing cells capable of generating sufficient elastin for tissue engineering applications
Solution Approach 2:
The patent uses elastogenic cues as intermediary substances that mediate between the adult vascular cells and the desired elastin synthesis outcome. These cues include growth factors (TGF-β, PDGF, FGF), cytokines, and small molecule compounds that act as signaling molecules to stimulate endogenous elastin production without requiring genetic modification or cell reprogramming
2Productivity
If vascular cells are stimulated to proliferate during tissue engineering, then more cells are available for tissue construction, but hyper-proliferation occurs during inflammatory vascular disease compromising tissue homeostasis
Solution Approach 1:
The patent applies local quality by creating spatially and temporally controlled delivery systems for elastogenic cues that provide high concentrations at the tissue engineering site to stimulate elastin synthesis, while maintaining normal physiological conditions elsewhere to prevent systemic hyper-proliferation and inflammatory responses. The localized application ensures productivity enhancement without compromising overall tissue homeostasis
3Ease of manufacture
If conventional tissue engineering materials are used, then the materials are readily available and easy to manufacture, but they lack the ability to upregulate elastin synthesis and provide adequate mechanical strength
Solution Approach 1:
The patent applies composite materials by combining conventional tissue engineering scaffolds (collagen, synthetic polymers) with elastogenic cue delivery systems. This creates a composite material system that maintains the ease of manufacture and biocompatibility of conventional materials while adding the functional capability to upregulate elastin synthesis and provide adequate mechanical strength for functional tissue regeneration
Solution Approach 2:
The patent applies universality by developing elastogenic cue formulations that can be integrated with multiple types of existing tissue engineering materials (collagen scaffolds, synthetic polymers, hydrogels). The elastogenic cues serve multiple functions: stimulating elastin synthesis, enhancing mechanical properties, and promoting tissue maturation, making them universally applicable across different tissue engineering platforms
Data Source
AI summary
Disclosed are elastogenic cues that can be utilized to encourage growth and development of elastin-containing cellular constructs. The elastogenic cues include hyaluronan fragments and oligomers, optionally in conjunction with growth factors and/or a source of copper ions. The elastogenic cues can up-regulate elastin matrix synthesis and by vascular smooth muscle cells. In addition to encouraging synthesis of elastin in a cellular matrix and organization into elastic fibers, the elastogenic cues can also stabilize the formed ECM matrix through suppression of elastin-laminin receptor (ELR). In addition, the elastogenic cues can inhibit cell hyper-proliferation (e.g., hyperplasia) common in inflammatory vascular disease.