Sclerostin Antagonist Coatings for Local Bone Growth Around Implants
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Solution Overview
Problem
Existing methods for altering bone growth are inadequate in promoting local bone growth or reducing bone overproduction, and there is a need for effective treatments for conditions such as osteoporosis, bone fractures, and kidney protection from chemical injury.
Innovation Solution
Administering therapeutic amounts of Sclerostin (Sost) or Wise antagonists, with or without an osteoconductive scaffold, to promote local bone growth, or using Sost or Wise agonists with antiresorptive agents to increase bone density systemically and locally, and administering antagonists to protect the kidney from chemical injury.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If systemic administration of Sost or Wise antagonists is used to increase bone density, then bone mineral density is improved systemically, but the treatment cannot provide localized bone growth promotion
Solution Approach 1:
The patent divides the bone treatment into two separate segments: a systemic component (Sost/Wise antagonist administration to increase overall bone density) and a local component (osteoconductive scaffold placement at specific fracture sites). This segmentation allows each component to address its specific function without interference, resolving the contradiction between systemic bone density improvement and localized bone growth promotion.
Solution Approach 2:
The osteoconductive scaffold serves as an intermediary device that delivers bone-stimulating factors locally to the fracture site. It mediates between the systemic treatment (antagonist administration) and the local requirement (bone growth at fracture site), enabling both systemic bone density increase and localized bone formation simultaneously.
2Productivity
If Sost or Wise antagonists are administered to promote bone growth, then bone formation is improved, but the treatment cannot effectively reduce bone overproduction in conditions like heterotopic ossification
Solution Approach 1:
The patent employs both antagonists (to block Sost/Wise and promote bone formation) and agonists (to activate Sost/Wise and reduce bone overproduction) depending on the clinical condition. This inversion of approach allows the same molecular target to be used for opposite therapeutic effects, resolving the contradiction between promoting bone formation and reducing bone overproduction.
Solution Approach 2:
The patent changes the functional parameter of Sost/Wise from blocked (antagonist) to activated (agonist) based on the clinical need. By altering the state of the molecular target, the treatment can adapt to different conditions: blocking Sost/Wise to promote bone formation in osteoporosis, or activating it to reduce bone overproduction in heterotopic ossification.
3Length of moving object
If local administration of Sost antagonist with osteoconductive scaffold is used, then local bone growth is promoted, but the device complexity increases
Solution Approach 1:
The patent merges the Sost antagonist protein directly with the osteoconductive scaffold material, creating a single integrated implant device. This combining of the biological agent with the structural support eliminates the need for separate administration systems, reducing device complexity while maintaining localized bone growth promotion.
Solution Approach 2:
The osteoconductive scaffold is designed to be self-delivering, with the Sost antagonist incorporated into the scaffold structure itself. The scaffold serves its own function of delivering the therapeutic protein without requiring external administration systems, thereby simplifying the overall device structure while achieving localized treatment.
4Quantity of substance
If combination of Sost antagonist and antiresorptive agent is administered systemically, then bone density is increased both systemically and locally, but the treatment regimen complexity increases
Solution Approach 1:
The patent performs preliminary action by placing the osteoconductive scaffold with embedded Sost antagonist at the fracture site before the systemic treatment begins. This preliminary local placement ensures that bone formation is stimulated at the specific site while the systemic antiresorptive agent works to prevent bone loss elsewhere, simplifying the coordination of multiple treatments.
Data Source
AI summary
The present invention provides a method of promoting local bone growth by administering a therapeutic amount of a Sost antagonist to a mammalian patient in need thereof. Preferably, the Sost antagonist is an antibody or FAB fragment selectively recognizing any one of SEQ ID NOS:1-23. The Sost antagonist may becoadministered together or sequentially with a matrix conducive to anchoring new bone growth. Orthopedic and Periodontal devices comprising an implantable portion adapted to be permanently implanted within a mammalian body and bearing an external coating of a Sost antagonist are also disclosed, as it a method ofincreasing bone density by administering to a mammalian patient a therapeutic amount of a Sost antagonist together with an antiresorptive drug.