Time-Controlled Glucose Hydrogel for Bone Tissue Engineering

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Solution Overview

Problem

Current glucose-releasing scaffolds for bone tissue engineering do not allow for controlled and prolonged release of glucose, leading to high cell death rates due to oxidative stress, hypoxia, and lack of vascularization, limiting the therapeutic effectiveness of transplanted mesenchymal stem cells.

Innovation Solution

A time-controlled hydrogel is developed, comprising a water-containing gelified polymer, a glucose polymer, and an enzyme that gradually hydrolyzes the glucose polymer, providing a prolonged and homogeneous release of glucose over several weeks, with the enzyme being encapsulated in polymeric particles to control the release rate.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If glucose is released quickly from the scaffold, then cell energy needs are met initially, but cell death occurs due to oxidative stress and hypoxia from uncontrolled glucose fluctuations

Engineering Contradiction:
Improveglucose release rateVSAvoidcell survival rate
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The hydrogel system dynamically adjusts glucose release rate through enzymatic hydrolysis of starch, transitioning from rapid initial release to sustained controlled release over time. The enzyme progressively breaks down starch polymers into glucose, creating a time-dependent release profile that matches cellular metabolic needs and prevents oxidative stress from sudden glucose spikes.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the physical-chemical parameters of glucose delivery by using starch polymer degradation instead of direct glucose release. This transforms the release kinetics from immediate diffusion to gradual enzymatic breakdown, controlling glucose concentration over time to maintain cell survival while meeting energy demands.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If the scaffold structure is simplified for ease of manufacture, then production becomes easier, but the release control precision is lost

Engineering Contradiction:
Improvescaffold fabricationVSAvoidglucose release control
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent creates a composite hydrogel system combining starch polymer, glucosidase enzyme, and crosslinking agents within a porous scaffold matrix. This composite structure integrates multiple functions: the starch provides glucose reservoir, the enzyme provides controlled release mechanism, and the crosslinked network provides structural integrity. The combination achieves precise release control without complicating the basic scaffold fabrication process.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The hydrogel system is self-regulating through the enzymatic hydrolysis mechanism. The glucosidase enzyme automatically converts starch to glucose in situ within the hydrogel matrix, providing intrinsic release control without requiring external control systems or complex manufacturing processes. The system self-adjusts glucose release based on the progressive degradation of starch polymers.

Inventive Principle:
Principle #25Self-service

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 achieves a prolonged and controlled release of glucose, enhancing the survival and functionality of transplanted cells by maintaining a stable glucose supply, improving vascularization, and promoting tissue regeneration.

Implementation Method 1

an enzyme capable of gradually hydrolysing said polymer into glucose

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

acts also as a viscosigen agent which limits the diffusion rate of both glucose and the hydrolysing enzyme

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentUS9931433B2Time-controlled glucose releasing hydrogels and applications thereof
Publication Date: 2018.04.03 CENT NAT DE LA RECH SCI (C N R S)
  • US9931433B2 patent drawing
  • US9931433B2 patent drawing
  • US9931433B2 patent drawing

AI summary

The present invention relates generally to a hydrogel releasing glucose in a time-controlled manner, to medical applications thereof, and to a method for preparing said hydrogel.