Gelatin Tyramine Hydrogel for Osteonecrosis Bone Regeneration
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Solution Overview
Problem
Current treatments for osteonecrosis, such as Legg-Calve-Perthes disease, face challenges in effectively promoting bone regeneration and preventing heterotopic ossification due to limited distribution and leakage of bone growth factors like BMP2, leading to incomplete bone repair and structural deformities.
Innovation Solution
A method involving the use of a bone growth-promoting hydrogel comprising gelatin tyramine, gelatin-heparin tyramine, or gelatin methacryloyl, loaded with BMP2 or other growth factors, which is injected into osteonecrotic bones to promote bone regeneration, utilizing a bone wash technique to prepare the site and ensure broad distribution without leakage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bone growth factors like BMP2 are injected into osteonecrotic bones, then bone regeneration is promoted, but the factors leak and distribute poorly leading to incomplete repair
Solution Approach 1:
The patent uses a hydrogel as an intermediary carrier to deliver bone growth factors (BMP2, VEGF, etc.) to the osteonecrotic bone site. The hydrogel matrix encapsulates the growth factors, preventing their leakage while enabling controlled release at the target site, thus resolving the contradiction between promoting bone regeneration and preventing factor loss
Solution Approach 2:
The patent modifies the physical and chemical parameters of the delivery system by using hydrogels with specific gelation temperatures, mesh sizes, and degradation rates. These parameter changes allow the growth factors to be retained within the hydrogel structure while maintaining bioactivity and enabling sustained release, thereby preventing leakage while ensuring effective bone regeneration
2Reliability
If bone growth factors are injected, then bone regeneration is promoted, but heterotopic ossification occurs due to uncontrolled distribution
Solution Approach 1:
The hydrogel acts as a localized intermediary that confines bone growth factors to the specific osteonecrotic site. This controlled localization prevents the uncontrolled distribution that causes heterotopic ossification, while still providing sufficient concentration to promote desired bone regeneration at the target site
Solution Approach 2:
The patent implements local quality control by ensuring bone growth factors are delivered specifically to the osteonecrotic region through the hydrogel carrier. This localized delivery creates high concentration at the target site for effective regeneration while minimizing off-target effects that would cause heterotopic ossification
3Stability of the object's composition
If traditional bone treatment methods are used, then some bone repair occurs, but structural deformities develop due to incomplete regeneration
Solution Approach 1:
The patent employs composite hydrogel materials that combine multiple functional components: gelatin or collagen matrices for structural support, crosslinking agents for stability, and embedded bone growth factors for regeneration. This composite approach ensures both structural integrity during repair and complete regeneration to prevent deformities
Solution Approach 2:
The hydrogel provides continuous delivery of bone growth factors over an extended period, ensuring sustained bone regeneration activity. This continuous action maintains structural integrity throughout the repair process and ensures complete regeneration, preventing the incomplete repair that leads to structural deformities
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 system effectively retains bioactive BMP2, achieving homogeneous bone regeneration, preventing heterotopic ossification, and restoring endochondral ossification in the subchondral region, with significant improvements in bone architecture and reduced bone voids.
Implementation Method 1
The hydrogel system effectively retains bioactive BMP2
Implementation Method 2
achieving homogeneous bone regeneration
Implementation Method 3
preparing a bone growth-promoting hydrogel comprising one or more bone growth-promoting agents in a hydrogel, the hydrogel comprising: at least one of gelatin tyramine (GT), gelatin-heparin tyramine (GHT)
Implementation Method 4
utilizing a bone wash technique to prepare the site
Implementation Method 5
loaded with BMP2 or other growth factors, which is injected into osteonecrotic bones to promote bone regeneration, achieving homogeneous bone regeneration, preventing heterotopic ossification, and restoring endochondral ossification
Data Source
AI summary
Provided herein are methods and compositions for treating bone osteonecrosis comprising: at least one of a Gelatin tyramine (GT), a gelatin-heparin tyramine (GHT), a gelatin methacryloyl (GelMa), a gelatin acryloyl (GelAC), collagen, or a hydrogel-forming peptide that can be formed ex vivo or in situ for the treatment of bone osteonecrosis; at least one bone growth promoting agent or a macrophage depletion reagent; and optionally one or more pharmaceutically acceptable carriers.