Injectable Hydrogel Biomaterial for Bone Regeneration in Compromised Wounds
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Solution Overview
Problem
Current therapies are inadequate for regenerating large bone volumes in compromised wounds due to vascular damage and immune responses that provoke hypoxia and inflammation, impairing bone neogenesis and promoting aberrant fibrosis.
Innovation Solution
A biomaterial comprising PEG, gelatin, and a glycosaminoglycan with a sulfated moiety, along with chondrogenic, osteogenic, and immunomodulatory cytokines, is used to promote bone regeneration by driving leukocyte differentiation down a regenerative pathway and reducing inflammatory response, optionally with mesenchymal stem cells and a porous scaffold for mechanical support.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If INFUSE (BMP-2 loaded collagen sponge) is used to drive bone formation, then bone formation is improved, but pro-inflammatory response increases
Solution Approach 1:
The patent introduces an intermediary substance (hydrogel composition with specific cytokines and growth factors) that mediates between the harmful pro-inflammatory environment and the desired bone regeneration outcome. This intermediary modulates the immune response to be pro-regenerative rather than pro-inflammatory, enabling bone formation without the harmful side effects of conventional BMP-2 products.
Solution Approach 2:
The patent changes the chemical and biological parameters of the wound environment by introducing a specific hydrogel composition containing anti-inflammatory cytokines (IL-10, TGF-β), growth factors (VEGF, FGF-2), and other bioactive molecules. These parameter changes transform the local microenvironment from pro-inflammatory to pro-regenerative, enabling bone formation without excessive inflammation.
2Device complexity
If vascular damage and immune responses are present in compromised wounds, then wound complexity increases, but bone neogenesis is impaired
Solution Approach 1:
The hydrogel composition acts as an intermediary that bridges the gap between the complex damaged wound environment and the bone regeneration process. It contains multiple bioactive components that simultaneously address vascular damage, immune responses, and promote bone neogenesis, thereby simplifying the overall healing process despite wound complexity.
Solution Approach 2:
The patent employs a multi-functional hydrogel composition that simultaneously performs multiple functions: anti-inflammatory cytokine delivery (IL-10, TGF-β), pro-angiogenic factor delivery (VEGF, FGF-2), and bone regeneration promotion. This universal approach addresses multiple wound complexity issues simultaneously rather than treating them separately.
3Duration of action of stationary object
If prolonged inflammation occurs in compromised wounds, then fibrosis increases, but bone regeneration is inhibited
Solution Approach 1:
The patent converts the harmful prolonged inflammatory response into a beneficial regenerative environment by introducing anti-inflammatory cytokines (IL-10, TGF-β) that redirect the immune response from fibrotic to regenerative. This transforms the harmful chronic inflammation into a beneficial controlled healing process that promotes bone formation rather than fibrosis.
Solution Approach 2:
The patent changes the temporal and intensity parameters of the inflammatory response by introducing bioactive molecules that shorten inflammation duration and shift its character from pro-fibrotic to pro-regenerative. The hydrogel composition modifies the inflammation trajectory to achieve resolution without fibrosis, enabling bone regeneration.
Data Source
AI summary
Biomaterials disclosed herein can comprise a hydrogel comprising PEG, gelatin, and a glycosaminoglycan with sulfated moiety; and chondrogenic, osteogenic, and immunomodulatory cytokines; wherein the biomaterial is capable of potentiating bone regeneration in a compromised wound while reducing inflammatory response. The glycosaminoglycan with sulfated moiety can comprise heparin, heparan sulfate, keratin sulfate, chondroitin sulfate, dermatan sulfate, and/or similar materials. The biomaterial can further comprise mesenchymal stem cells (MSCs), a crosslinking initiator, microparticles and nanoparticles, and/or other materials. The biomaterial can be injectable into a wound, or the biomaterial can be loaded in, or further comprise a porous scaffold providing mechanical support for other components of the biomaterial, such that it can be implanted into a wound.