Multilayer Collagen Membrane for Tissue Regeneration

Solution Overview

Problem

Existing single-layer collagen membranes are insufficient for effective cartilage tissue regeneration due to limited cell growth guidance and pyrogenicity, necessitating a multilayer membrane with improved structural properties and reduced antigenicity.

Innovation Solution

A structured multilayer membrane composed of pure type I collagen with reduced telopeptides, featuring a closed barrier layer and a porous layer for cell migration, fabricated through freeze-drying and controlled hydration, with optional cross-linking and impregnation with glycosaminoglycans and chondrocytes, to promote tissue regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a single-layer homogeneous collagen membrane is used, then the structure is simple and easy to manufacture, but it fails to provide sufficient cell growth guidance and tissue regeneration capability

Engineering Contradiction:
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The membrane is divided into multiple layers with different porosity values (first layer: 20-40%, second layer: 60-80%, third layer: 20-40%). Each layer serves a specific function: the dense outer layers provide structural support and control, while the porous middle layer facilitates cell ingrowth and tissue regeneration. This segmentation resolves the contradiction by maintaining manufacturing feasibility through a systematic multi-layer structure while significantly improving tissue regeneration capability through differentiated functional zones.

Inventive Principle:
Principle #1Segmentation

2Strength

If collagen membranes with terminal telopeptides are used, then the membrane provides structural integrity, but it exhibits pyrogenicity and antigenic determinants

Engineering Contradiction:
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent removes terminal telopeptides from the collagen structure through enzymatic treatment or chemical modification. This extraction eliminates the antigenic determinants and pyrogenic properties while preserving the triple-helix structure and mechanical strength of the collagen. The modified collagen maintains structural integrity necessary for membrane function while removing harmful immunogenic components.

Inventive Principle:
Principle #2Taking out (Extraction)

3Strength

If a dense collagen structure is used, then the membrane provides structural support, but it prevents cell penetration and tissue ingrowth

Engineering Contradiction:
Core Design Contradiction:
StrengthVSEase of operation

Solution Approach 1:

The membrane exhibits spatially varying porosity: the first and third layers have low porosity (20-40%) providing structural support and mechanical strength, while the second layer has high porosity (60-80%) specifically designed to facilitate cell penetration and tissue ingrowth. This local quality differentiation resolves the contradiction by providing both structural integrity and cellular accessibility in different regions of the same membrane structure.

Inventive Principle:
Principle #3Local quality

4Duration of action of stationary object

If the membrane absorption time is extended, then the membrane provides prolonged support, but it delays the natural healing and regeneration process

Engineering Contradiction:
Core Design Contradiction:
Duration of action of stationary objectVSProductivity

Solution Approach 1:

The membrane is designed with progressive degradation characteristics where different layers degrade at different rates based on their composition and porosity. The highly porous middle layer degrades faster as cells invade and replace it with native tissue, while the denser outer layers provide prolonged structural support. This dynamic, staged degradation resolves the contradiction by matching membrane persistence to the temporal requirements of different healing phases.

Inventive Principle:
Principle #15Dynamics

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 membrane supports controlled tissue regeneration by guiding cell growth, reducing antigenicity, and extending membrane absorption, while allowing for the controlled release of active components, enhancing the healing process and preventing decomposition during tissue repair.

Implementation Method 1

a homogeneous porous membrane is created by freeze-drying of plates of frozen collagen gel

Methodology Applied
Scientific EffectFreeze-drying: Freeze Drying

Implementation Method 2

the structure obtained is stabilized by rapid freezing

Methodology Applied
Scientific EffectRapid freezing: Freezing

Implementation Method 3

the membrane is then wetted by controlled application of a mixture of water and additives

Methodology Applied
Scientific EffectWetting: Wetting

Data Source

PatentEP2178458B1Procedure for the manufacture of a structured multilayer membrane, the structured multilayer membrane and its uses
Publication Date: 2014.11.19

AI summary

A procedure for the manufacture of a structured multilayer membrane, suitable for use in surgical reconstructions of ligament, bone or cartilage tissue, the membrane being made of collagen I freed from telopeptides (partly at least) and containing a minimum of one barrier-structure layer closed to cell ingrowth and one sponge-like structure layer open to cell ingrowth, the procedure consisting of steps where a collagen suspension is frozen in a flat bed into plates which are then vacuum-dried at a temperature below their thawing temperature, the sponge-like membranes are wetted by a controlled procedure in which a limited amount of water, smaller than as sufficient for hydration of the whole membrane thickness, is applied to them, the wetted membrane is conveniently allowed to rest at a reduced temperature of 0°C to 10°C for the moisture to equilibrate inside the structure, the thickness is modified as appropriate by applying mechanical pressure, one side is conveniently discriminated from the other by applying a tread pattern or dye, the membrane is re-frozen and dried at a reduced pressure, controlled heating being applied during a later stage of the drying procedure for the moisture temperature to rise to above the thawing temperature. The invention also covers the membrane so obtained and its use.