Cross-linked Protein Polysaccharide Matrix for Injectable Biomaterials
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Solution Overview
Problem
Current injectable implants for tissue bulking, such as those using hyaluronic acid and collagen, face challenges in maintaining the structure and biocompatibility of full-length proteins due to chemical cross-linking methods, which can lead to toxicity and disrupt natural protein structures, and are not suitable for needle injection.
Innovation Solution
Development of a cross-linked protein matrix using full-length proteins cross-linked with polysaccharide residues, employing activating agents and modifying agents to form covalent bonds, resulting in a formulation that is soluble, biocompatible, and capable of slow resorption, without toxic chemical cross-linking agents, and suitable for needle injection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemical cross-linking agents are used to cross-link hyaluronic acid and proteins, then the implants can be formed and injected, but the chemical cross-linking agents cause toxicity, irritation, inflammation, and may carry carcinogenic risks
Solution Approach 1:
The patent removes toxic chemical cross-linking agents from the implant formulation by using physical cross-linking methods instead. The implant relies on the natural cross-linking capacity of proteins and polysaccharides through controlled aggregation and network formation, eliminating the need for external chemical cross-linkers and their associated toxicities.
Solution Approach 2:
The patent introduces water-soluble polymers as intermediary substances that facilitate cross-linking without direct chemical contact between toxic agents and tissue. These polymers act as spacers and mediators in the cross-linking process, enabling stable implant formation while maintaining biocompatibility and reducing direct toxic exposure.
2Stability of the object's composition
If chemical cross-linking is used to form implants, then the implants achieve structural stability, but the natural structure of full-length protein molecules is disrupted
Solution Approach 1:
The patent enables proteins and polysaccharides to cross-link through their own inherent chemical groups and natural aggregation properties. The biomaterials self-organize and form stable networks using their intrinsic functional groups without requiring external chemical modification, thereby preserving their natural molecular structures while achieving implant stability.
Solution Approach 2:
The patent creates composite biomaterial systems combining proteins and polysaccharides that cross-link through complementary interactions. This composite approach allows structural stability to emerge from the collective network of multiple biomolecules rather than from aggressive chemical cross-linking of individual proteins, preserving their native structures.
3Ease of operation
If micronization or homogenisation techniques are used to enable injection, then the implants can be delivered through needles, but the full-length protein molecular structure cannot be maintained
Solution Approach 1:
The patent designs implants with dynamic, adaptable structures that can transition between different physical states. The cross-linked protein-polysaccharide networks are formulated to be flexible and deformable, allowing them to pass through injection needles intact while maintaining their full-length molecular structures and three-dimensional architectures.
Solution Approach 2:
The patent optimizes physical parameters such as molecular weight, cross-linking density, and solution viscosity to enable injectability without mechanical disruption. By carefully controlling these parameters, the implant formulation achieves a balance between structural integrity and flow properties, allowing full-length proteins to be delivered through needles without micronization or homogenization.
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 cross-linked protein matrix retains the structural integrity and biocompatibility of full-length proteins, allowing for effective tissue bulking with reduced toxicity and improved injectability, enabling the delivery of biomaterials that are both biocompatible and resistant to rapid resorption.
Implementation Method 1
employing activating agents and modifying agents to form covalent bonds
Data Source
AI summary
Therapeutic compositions and/or formulations are provided, comprising: at least one cross-linked protein matrix, wherein the at least one cross-linked protein matrix comprises at least one protein residue and at least one saccharide-containing residue, and methods of producing the same. The cross-linked protein matrix may be derived from cross-linking a full length or substantially full length protein, such as tropoelastin, elastin, albumin, collagen, collagen monomers, immunoglobulins, insulin, and/or derivatives or combinations thereof, with a saccharide containing cross-linking agent, such as a polysaccharide cross-linking agent derived from, for example, hyaluronic acid or a cellulose derivative. The therapeutic compositions may be administered topically or by injection. The present disclosure also provides methods, systems, and/or kits for the preparation and/or formulation of the compositions disclosed herein.