Injectable BMP-2 Solution for Bone Defect Repair
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Solution Overview
Problem
Current methods for delivering bone morphogenetic protein 2 (BMP-2) require a stationary matrix, which can be impractical for bone defects in high-circulation areas and difficult to administer percutaneously, especially for bone defects where a matrix may dislodge and cause thrombosis, necessitating a new approach for effective bone regeneration without a matrix.
Innovation Solution
An injectable solution of BMP-2 in an aqueous carrier, such as saline or phosphate buffered saline, is administered directly to bone defects, allowing for osteogenesis, osteoinduction, and osteoconduction without the need for a stationary matrix, with dosages ranging from 20 μg to 5000 μg, facilitating easier administration and reducing the risk of matrix-related complications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a stationary matrix is used to deliver BMP-2, then the biological activity and conformational integrity of the protein is preserved, but the ease of administration and applicability to high-circulation area bone defects is reduced
Solution Approach 1:
The patent changes the physical state of BMP-2 from a matrix-bound formulation to an injectable solution formulation. This parameter change allows the protein to be administered percutaneously to bone defects while maintaining its biological activity through optimized solution conditions including pH control (pH 6.0-8.0), ionic strength adjustment, and the use of stabilizing excipients such as HEPES buffer, EDTA, and various sugars or polyols that prevent protein aggregation and degradation in solution.
2Reliability
If a stationary matrix is used to deliver BMP-2, then the protein is protected from degradation, but the risk of thrombosis in high-circulation areas increases
Solution Approach 1:
The patent extracts BMP-2 from the stationary matrix formulation and delivers it as a free-standing injectable solution. This removes the matrix material that could dislodge and cause thrombosis in high-circulation areas such as the femur, while still protecting the protein from degradation through optimized solution chemistry including chelating agents like EDTA that prevent metal-catalyzed oxidation, and stabilizing excipients that maintain protein conformation.
3Ease of operation
If an injectable solution is used to deliver BMP-2, then the ease of percutaneous administration is improved, but the protection from bodily fluid degradation must be achieved through alternative means
Solution Approach 1:
The patent introduces various excipients as intermediaries to protect BMP-2 from degradation in the injectable solution. These include chelating agents like EDTA that sequester metal ions to prevent oxidative degradation, buffering agents like HEPES that maintain optimal pH to prevent acid-base catalyzed degradation, and stabilizing excipients such as sugars (sucrose, trehalose) or polyols (glycerol, sorbitol) that form protective hydration shells around the protein and prevent aggregation. These intermediaries enable the protein to remain stable in the aqueous injectable formulation.
Data Source
AI summary
A method of treating a bone defect is provided. The method comprises administering to the bone defect an injectable solution comprising about 20 μg to about 5000 μg of bone morphogenetic protein-2 (BMP-2) in an aqueous carrier. Kits and methods of making are also provided.