Anionic Citrate Biomaterial Composition for Controlled BMP Release
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Solution Overview
Problem
Current bone grafting methods, such as autogenous bone grafting and BMP treatments, suffer from limitations like donor site deformity, pain, infection, supply limitations, and adverse effects due to high BMP doses, while existing BMP delivery systems face issues with burst release and anticoagulant risks from heparin use.
Innovation Solution
Development of anionic citrate-based compositions comprising citrate, polyol, and anionic moieties like sulfate, sulfonate, or phosphate for controlled protein binding and release, utilizing electrostatic interactions and tunable surface charges to manage protein delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high dose of BMP is administered to achieve effective bone regeneration, then bone formation efficacy is improved, but adverse effects such as inflammatory reactions, soft tissue hematomas, ectopic bone formation, and cancer increase
Solution Approach 1:
The patent modifies the delivery system parameters by using anionic citrate-based polymers with specific charge densities and molecular weights to control BMP release kinetics, enabling effective bone regeneration at lower BMP doses with reduced adverse effects
Solution Approach 2:
The patent creates composite delivery systems combining anionic citrate-based polymers with BMP molecules, where the polymer-BMP complex provides controlled release and localized delivery, improving efficacy while reducing systemic adverse effects
2Reliability
If collagen-based delivery systems are used for BMP delivery, then biocompatibility is improved, but burst release occurs resulting in only 5% of BMP remaining after 2 weeks
Solution Approach 1:
The patent changes the delivery system composition from collagen to anionic citrate-based polymers with specific electrostatic properties, enabling strong electrostatic binding to BMP and controlled release kinetics while maintaining biocompatibility
Solution Approach 2:
The patent discards the collagen-based system's inadequate retention property and recovers the biocompatibility advantage by transitioning to citrate-based polymers that provide both strong BMP binding and sustained release
3Quantity of substance
If heparin is bound to carriers to reduce BMP dosage and decrease release rate, then protein binding capability is improved, but anticoagulant effect increases causing surgical complications
Solution Approach 1:
The patent replaces heparin with anionic citrate-based polymers that provide equivalent protein binding capability without the anticoagulant side effects, creating a safer delivery system
Solution Approach 2:
The patent uses anionic citrate-based polymers as intermediary carriers that mediate BMP delivery through electrostatic interactions, replacing heparin's binding function while eliminating its harmful anticoagulant effects
4Reliability
If autogenous bone grafting is performed to achieve bone formation, then bone regeneration is improved, but donor site deformity, pain, infection, and supply limitations occur
Solution Approach 1:
The patent introduces anionic citrate-based polymer-BMP complexes as intermediary delivery systems that mediate bone regeneration without requiring autogenous bone harvesting, eliminating donor site complications
Solution Approach 2:
The patent extracts the bone-regenerating function from the autogenous graft procedure itself and isolates it into a deliverable BMP-based formulation, separating the therapeutic effect from the harmful harvesting process
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 citrate-based compositions provide controlled and prolonged release of proteins like BMP-2, reducing the dosage requirements and minimizing adverse effects, with improved biocompatibility and reduced burst release.
Implementation Method 1
The citrate-based compositions provide controlled and prolonged release of proteins like BMP-2, reducing the dosage requirements and minimizing adverse effects, with improved biocompatibility and reduced burst release
Implementation Method 2
utilizing electrostatic interactions and tunable surface charges to manage protein delivery
Data Source
AI summary
The present disclosure provides anionic citrate-based composition for use in regenerative applications. The disclosed composition may take the form of a scaffold and generally includes (i) a citrate component, (ii) a diol, and (iii) an anionic moiety. The anionic moiety may include one or more of a sulfate, sulfonate, phosphate, phosphonate, sulfamate, or carboxylic acid, The sulfate and/or sulfonate containing moiety may be conjugated via an amidation reaction, esterification, and/or substitution reaction with a sulfur trioxide complex. A peptide may be conjugated to a surface of the composition.