3D Cardiac Patch Using Segmented Fibrin Scaffold for Vascularization
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Solution Overview
Problem
Current methods for reconstructing functional heart tissue face challenges with vascularization and replicating the organizational, mechanical, and elastic properties of native myocardium, limiting the effectiveness of conventional tissue scaffolds in replacing large-sized tissue defects.
Innovation Solution
A three-dimensional artificial cardiac patch is fabricated by coating a substrate with an organic polymer, forming a biodegradable gel-based support scaffold, and seeding neonatal cardiac cells, which self-organize into a real cardiac layer capable of spontaneous contraction and angiogenic bud formation, using a fibrin gel scaffold to support nutrient delivery and maintain cell viability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional tissue scaffolds are used for heart tissue reconstruction, then structural support is provided, but vascularization is insufficient
Solution Approach 1:
The invention divides the scaffold into multiple functional layers: an outer porous scaffold providing structural support, and inner hydrogel microspheres containing vascular endothelial cells. This segmentation allows each component to specialize - the scaffold provides mechanics while the hydrogel spheres provide vascularization, resolving the contradiction between structural support and vascularization.
Solution Approach 2:
The hydrogel microspheres act as intermediaries between the structural scaffold and the cardiac tissue. They contain pre-formed vascular networks that serve as a bridge, facilitating blood vessel formation and nutrient delivery to the engineered heart tissue, thereby improving vascularization without complicating the overall scaffold design.
2Area of stationary object
If tissue scaffolds are designed to support large injured areas, then coverage is improved, but mechanical and elastic properties of native myocardium are not replicated
Solution Approach 1:
The invention uses composite materials combining a porous scaffold (for structural integrity and large area coverage) with hydrogel microspheres (for mechanical compliance and elastic properties). This composite structure allows the patch to cover large injured areas while replicating the mechanical and elastic properties of native myocardium through the viscoelastic characteristics of the hydrogel component.
3Force
If cell density is increased to improve contractile force, then contractility is enhanced, but cell viability may be compromised
Solution Approach 1:
The invention applies local quality by creating zones of different cell densities within the hydrogel microspheres. High-density regions provide strong contractile force where needed, while lower-density regions ensure adequate nutrient diffusion and oxygen supply to maintain cell viability. The porous scaffold structure also creates local channels for nutrient transport, allowing high cell densities to coexist with high viability.
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 artificial cardiac patch exhibits robust cellular division, electromechanical coupling, and contractile forces comparable to native heart tissue, with optimal cell densities achieving higher contractile forces and viability, addressing the limitations of previous scaffolds in vascularization and mechanical properties.
Implementation Method 1
coating a substrate with an organic polymer
Implementation Method 2
forming a biodegradable gel-based support scaffold on top of the organic polymer coating
Implementation Method 3
culturing the neonatal cardiac cells in vitro to form a real cardiac layer, under culture conditions that are suitable for the cells to self-organize into a monolayer
Data Source
AI summary
In some embodiments, the present disclosure provides a method for fabricating a three-dimensional artificial cardiac patch construct. In some embodiments, such method includes the steps of coating a substrate with an organic polymer; allowing the organic polymer coating to air dry; mounting anchors on the organic polymer coating; and sterilizing the organic polymer coating and the anchors. In further embodiments, the method includes the steps of forming a biodegradable gel-based support scaffold on top of the organic polymer coating and seeding the biodegradable gel-based support scaffold with neonatal cardiac cells. In yet further embodiments, the method comprises culturing the neonatal cardiac cells in vitro to form a real cardiac layer, under culture conditions that are suitable for the cells to self-organize into a monolayer and detach from the substrate to form the three-dimensional cardiac patch. In some embodiments, the present disclosure pertains to a method of treatment of cardiac tissue injury in a subject in need thereof. In some embodiments, the method includes implanting the three-dimensional artificial cardiac patch described above in the injured area of the subject. In another embodiment the present disclosure provides a composition comprising the three-dimensional artificial cardiac patch described above. Additional embodiments of the present disclosure pertain to a medicament including the three-dimensional artificial cardiac patch described above.