Multidomain Peptide Hydrogel for Stable Angiogenesis
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Solution Overview
Problem
Current techniques for promoting angiogenesis in ischemic tissues, such as those used in neovascularization, have been hampered by the formation of small, immature vessels that fail to integrate with the host vasculature, lack pericyte support, and are short-lived, leading to modest and incomplete tissue recovery.
Innovation Solution
A multidomain peptide composition that self-assembles into a hydrogel scaffold, featuring a bioactive peptide sequence, enzymatic cleavage signaling, and specific structural domains, allowing for non-invasive delivery and promoting the formation of mature, stable vessels with pericyte support and efficient resorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If growth factors are injected to promote angiogenesis, then blood vessel growth is stimulated, but the vessels formed are small, immature, and fail to integrate with host vasculature
Solution Approach 1:
The invention uses a composite hydrogel system combining multiple peptides (RGD peptide for cell adhesion, VEGF-mimetic peptide for angiogenesis, and collagen-mimetic peptide for structural support) to create a multifunctional material that simultaneously promotes vessel formation, ensures maturity, and enables integration with host vasculature
Solution Approach 2:
The angiogenic peptide is divided into multiple functional domains: an N-terminal domain for self-assembly and structural integrity, a central domain with enzymatic cleavage sites for controlled activation, and a C-terminal domain containing the bioactive VEGF-mimetic sequence for endothelial cell interaction
2Productivity
If growth factors are used to stimulate neovascularization, then new blood vessels form, but the vessels lack pericyte support and are short-lived
Solution Approach 1:
The hydrogel is pre-loaded with pericyte-recruiting signals and structural cues before implantation, creating a pre-prepared microenvironment that guides pericyte migration and attachment, ensuring vessel stabilization occurs concurrently with vessel formation rather than as a subsequent step
Solution Approach 2:
The peptide composition undergoes enzymatic cleavage in vivo, transforming from an inactive precursor state to an active state where bioactive sequences are released, changing the physical and biological parameters of the hydrogel to promote sustained vessel maturation and pericyte recruitment
3Reliability
If VEGF is administered to reverse ischemia, then some tissue recovery occurs, but most of the growth factor diffuses into the lymphatic system reducing efficacy
Solution Approach 1:
The self-assembling peptide hydrogel acts as an intermediary carrier that binds and retains the VEGF-mimetic peptide at the implantation site, preventing premature diffusion into lymphatic systems while controlling the release rate to match tissue regeneration needs
Solution Approach 2:
The hydrogel system is self-assembling and self-regulating, forming its three-dimensional structure autonomously through peptide self-assembly and maintaining growth factor retention through intrinsic molecular interactions without requiring external stabilization mechanisms
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 peptide composition effectively forms stable angiogenic vessels that integrate with the host vasculature and resorb appropriately, enhancing tissue healing and vascularization in ischemic tissues.
Implementation Method 1
the peptide self-assembles to form a hydrogel scaffold
Implementation Method 2
The second domain comprises two to six repeats of an amino acid sequence consisting of a hydrophilic amino acid and a hydrophobic amino acid. The second domain drives the self-assembly of the peptide into a β-sheet structure.
Implementation Method 3
A third domain comprises a specific enzymatic cleavage signaling sequence. The third domain, in at least one embodiment, is embedded within the second domain. the addition of a cleavage signal in the peptide facilitates diffusion of the bioactive peptide enhancing its biological effect
Implementation Method 4
The hydrogel structure quickly recovers following disruption through shearing thereby allowing the composition to be injected non-invasively or minimally invasively with a syringe-needle or catheter delivery.
Data Source
AI summary
The present disclosure provides a composition comprising a multi-domain peptide capable of self-assembly into a nanofibrous hydrogel structure capable of stimulating a robust angiogenic response. In one embodiment, the composition comprises a short 15 amino acid VEGF-165 peptide mimic conjugated to a 16 amino acid multidomain peptide. A method for promoting angiogenesis and/or treating ischemic wounds in a subject is also provided.