Pullulan Collagen Hydrogel Scaffold for Scar Reduction

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current skin substitutes for wound healing are limited by poor tissue integration, susceptibility to microbial infection, calcification, and the formation of scar tissue, leading to inadequate regeneration and healing outcomes.

Innovation Solution

A pullulan-based collagen hydrogel film with controlled porosity is fabricated using salt-induced phase inversion and cross-linking, providing a biodegradable scaffold that mimics the dermal ultrastructure, allowing for regenerative cell growth and tissue repair while minimizing scarring.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If primitive animal collagen scaffolds are used for skin substitution, then a conduit for tissue ingrowth is provided, but poor tissue integration occurs resulting in scar tissue formation rather than regenerated skin

Engineering Contradiction:
Improvetissue integrationVSAvoidscar tissue formation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses a composite material system combining decellularized extracellular matrix (dECM) with natural collagen. The dECM provides bioactive signals and structural organization, while collagen provides mechanical support and scaffold architecture. This composite approach creates a more physiologically relevant environment that promotes proper tissue integration and prevents scar formation, overcoming the limitations of primitive collagen scaffolds alone.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent modifies the physical and chemical parameters of the scaffold by controlling the porosity, pore size distribution, and cross-linking density of the dECM-collagen composite. These parameter changes create an optimized microenvironment that supports cell migration, proliferation, and differentiation, thereby improving tissue integration and preventing pathological scar tissue formation.

Inventive Principle:
Principle #35Parameter changes

2Strength

If synthetic polymers are used for tissue engineering, then structural integrity is provided, but cells cannot remodel them after implantation and they are highly susceptible to microbial infection

Engineering Contradiction:
Improvestructural integrityVSAvoidcell remodeling capability
Core Design Contradiction:
StrengthVSAdaptability or versatility

Solution Approach 1:

The patent employs a highly porous dECM-collagen scaffold structure with controlled pore sizes that mimic native tissue architecture. This porous structure allows cell penetration, migration, and remodeling while maintaining structural integrity. The natural origin of the materials provides appropriate mechanical properties and biochemical cues that enable cell adaptation and remodeling, unlike synthetic polymers.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The dECM-collagen scaffold is designed to be dynamically remodeled by cells after implantation. Cells can degrade and rebuild the matrix components, adapting the scaffold to their needs over time. This self-service capability allows the implant to evolve from a static structure to a living, integrated tissue, providing both initial structural support and long-term adaptability.

Inventive Principle:
Principle #25Self-service

3Ease of manufacture

If native dermal sources such as decellularized cadaveric skin are used, then a dermal scaffold is provided, but limitations exist due to cost, donor availability, and disease transmission concerns

Engineering Contradiction:
Improvescaffold availabilityVSAvoiddisease transmission risk
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and isolates the beneficial extracellular matrix components from donor tissue through decellularization processes, removing all cellular material that could transmit disease. This extraction leaves behind the acellular dECM scaffold with its bioactive molecules and structural organization, eliminating disease transmission risk while preserving the functional benefits of native tissue matrices.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs alternative sources for dECM production that are more readily available and cost-effective than cadaveric skin, such as cultured cell-derived matrices or engineered ECM constructs. These approaches provide scalable, controlled production of scaffolds without the logistical and safety issues of donor-derived tissues.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 scaffold supports viable cell growth, enhances wound healing by promoting regenerative cell migration and tissue regeneration, and reduces the formation of scar tissue, offering improved handling characteristics and durability for effective skin repair.

Implementation Method 1

The hydrogel is fabricated with salt-induced phase inversion and cross-linking to form a reticular scaffold

Methodology Applied
Scientific EffectPhase inversion: Phase Change

Implementation Method 2

The hydrogel is fabricated with salt-induced phase inversion and cross-linking to form a reticular scaffold

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Data Source

PatentUS9636362B2Pullulan regenerative matrix
Publication Date: 2017.05.02 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US9636362B2 patent drawing
  • US9636362B2 patent drawing
  • US9636362B2 patent drawing

AI summary

Compositions and methods are provided for the manufacture and use of a pullulan-based collagen hydrogel film with controlled porosity. The hydrogel is fabricated with salt-induced phase inversion and cross-linking to form a reticular scaffold. This soft collagen scaffold displays excellent handling characteristics, durability, and a porous dermal-like ultrastructure that is maintained in vitro. Cells, including cells involved in tissue repair, are viably sustained within the scaffold. The hydrogel films are biodegradable, and find particular use in wound healing, where the hydrogel scaffold can be replaced by dermal cells over time.