Collagen-Binding Growth Factor Release at Wound Healing Stages
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapeutics are unable to promote regeneration of heart tissue after a heart attack, and existing growth factor treatments are limited by targeted delivery challenges and off-target effects.
Innovation Solution
Collagen-binding agents, comprising a therapeutic agent, a protease cleavage site, and a collagen-binding domain, are designed for spatial and temporal regulation, targeting exposed collagen fibrils during wound healing and releasing the therapeutic agent at the appropriate phase using MMP upregulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If growth factors are administered as conventional therapeutics, then heart tissue regeneration is promoted, but targeted delivery is difficult and off-target effects occur
Solution Approach 1:
The patent uses collagen-binding domains as intermediary molecules that mediate the delivery of therapeutic growth factors to specific locations. The collagen-binding domain binds to exposed collagen fibrils at the wound site, serving as a carrier that releases the growth factor locally, thereby achieving targeted delivery and reducing off-target effects.
Solution Approach 2:
The invention implements local quality by designing the growth factor to be released specifically at the wound site where collagen exposure occurs. The collagen-binding domain ensures the therapeutic agent is localized to the area needing treatment, providing spatially-specific action rather than systemic distribution.
2Speed
If growth factors are released immediately upon administration, then rapid effect is achieved, but spatial and temporal regulation is lost
Solution Approach 1:
The growth factor is pre-bound to the collagen-binding domain in an inactive or stored state. The collagen-binding domain is designed to be released only when collagen is exposed during wound healing, triggering the release of the growth factor at the appropriate time and location. This preliminary binding ensures regulated release rather than immediate action.
Solution Approach 2:
The invention introduces dynamics by making the growth factor release conditional and reversible. The collagen-binding domain can bind to collagen and release the growth factor based on the dynamic conditions of wound healing, allowing the system to adapt to the physiological state rather than following a fixed release schedule.
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 collagen-binding agents effectively promote heart tissue remodeling and prevent heart failure by delivering growth factors like FGF at the right stage of wound healing, reducing off-target effects and improving clinical safety.
Implementation Method 1
The collagen-binding domain is a polypeptide selected from the group consisting of SEQ ID NOs: 6-53, a polypeptide having at least 90% sequence identity to SEQ ID NOs: 6-53, and a fragment of at least 8 consecutive amino acids of SEQ ID NOs: 6-53
Implementation Method 2
the protease cleavage site is the cleavage site of a matrix metalloproteinase (MMP)
Data Source
AI summary
The present invention provides collagen-binding agents that can be used to treat wounds, ischemic heart disease, and other conditions. The collagen-binding agents comprise a therapeutic agent, a protease cleavage site, and a collagen-binding domain. The present invention further provides pharmaceutical compositions and biomedical devices comprising the disclosed collagen-binding agents, as well as methods for treating a condition using the collagen-binding agents.