Supramolecular Alginate Hydrogel for Cell Viability and Vascularization

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Solution Overview

Problem

Current tissue engineering techniques face challenges in regenerating complex, hybrid tissues, and there is a need for materials and methods to deliver cells and drugs effectively for wound healing and tissue restoration, requiring biomaterial platforms that mimic natural tissue mechanics and alter properties like cell adhesion and neovascularization.

Innovation Solution

A hydrogel composition incorporating alginate, methacrylated alginate, β-cyclodextrin, heparin, and arginylglycylaspartic acid, which are covalently bound, along with additional crosslinking components, to create a supramolecular complex that encapsulates living cells and bioactive compounds, promoting cell viability and tissue development.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If simple hydrogels are used for cell encapsulation, then ease of manufacture is improved, but the ability to mimic natural tissue mechanics and promote complex tissue regeneration deteriorates

Engineering Contradiction:
Improveease of manufactureVSAvoidability to mimic natural tissue mechanics
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent employs composite hydrogel materials combining multiple polymers (alginate, gelatin, hyaluronic acid) with embedded growth factors and signaling molecules. This composite structure enables the material to simultaneously provide mechanical support, biochemical cues, and controlled release functionality, thereby mimicking the complex extracellular matrix of natural tissues while remaining manufacturable through established hydrogel crosslinking techniques.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The hydrogel composition incorporates spatially distributed biochemical cues including cell-adhesion peptides (RGD), growth factors (VEGF, FGF), and morphogens arranged in specific zones within the matrix. This local quality variation allows different regions of the hydrogel to provide tailored mechanical properties and biochemical signals that guide specific cellular responses such as differentiation, migration, and vascularization at appropriate locations.

Inventive Principle:
Principle #3Local quality

2Reliability

If advanced supramolecular complexes are used to promote tissue regeneration, then tissue development is improved, but device complexity increases

Engineering Contradiction:
Improvecell viabilityVSAvoiddevice complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The supramolecular hydrogel complex exhibits self-assembly properties where constituent polymers, crosslinkers, and bioactive molecules spontaneously organize into functional three-dimensional networks upon contact with physiological conditions. This self-service mechanism eliminates the need for complex external assembly equipment or multi-step fabrication processes, thereby achieving reliable cell viability support through autonomous molecular organization rather than mechanically complex device assembly.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent utilizes changes in physical-chemical parameters such as pH, temperature, and ionic strength to trigger phase transitions and self-assembly of hydrogel components. For example, temperature-responsive gelation or pH-dependent crosslinking allows the system to transform from soluble precursors to gelous networks under physiological conditions, providing reliable cellular microenvironments through simple parameter changes rather than complex device operations.

Inventive Principle:
Principle #35Parameter changes

3Strength

If multiple crosslinking components are incorporated to enhance material properties, then strength is improved, but manufacturing precision requirements increase

Engineering Contradiction:
ImprovestrengthVSAvoidmanufacturing precision
Core Design Contradiction:
StrengthVSManufacturing precision

Solution Approach 1:

The patent incorporates pre-functionalized polymer chains with predetermined crosslinking sites and embedded bioactive motifs during the synthesis stage. These pre-prepared macromers contain built-in crosslinkable groups (e.g., methacrylate, epoxy) and cell-adhesion sequences that are already positioned optimally before hydrogel formation. This preliminary action eliminates the need for precise real-time control of crosslinking reactions during manufacturing, as the molecular architecture is predetermined to self-organize into strong networks with appropriate mechanical properties through simple mixing and crosslinking procedures.

Inventive Principle:
Principle #10Preliminary action

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 hydrogel composition supports long-term cell viability, facilitates vascular development, and enables the delivery of viable cells and drugs, effectively treating various diseases and wounds by mimicking natural tissue properties and promoting cellular functions such as cell growth and differentiation.

Implementation Method 1

the at least one pharmaceutically active compound is non-covalently bound to the hydrogel composition through a guest-host interaction with the a β-cyclodextrin moiety

Methodology Applied
Scientific EffectGuest-host interaction:

Implementation Method 2

the β-cyclodextrin (β-CD) and the at least one additional component are each covalently bound to the alginate or methacrylated alginate

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Data Source

PatentUS11331415B2Supramolecular alginate materials for biomedical applications
Publication Date: 2022.05.17 UNIVERSITY OF VERMONT
  • US11331415B2 patent drawing
  • US11331415B2 patent drawing
  • US11331415B2 patent drawing

AI summary

The present invention relates to the unexpected discovery of novel hydrogel formulations that allow for the encapsulation and delivery of living cells and/or drugs to a subject in need thereof. In certain embodiments, the hydrogel compositions of the invention comprise bound bioactive molecules that promote long-term cell viability and allows for the development of vasculature. The invention further provides methods of delivering viable cells and/or drugs to a subject comprising administering the compositions of the invention to the subject in need thereof.