Oligopeptide Sequences Enhancing BMP Receptor Binding for Dental Implants

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Solution Overview

Problem

Existing oligopeptides used for enhancing osteointegration and osteogenesis in dental implants have low binding affinity to BMP-specific receptors, leading to inadequate osteoblastic differentiation and prolonged induction periods in implant surgeries.

Innovation Solution

Development of oligopeptides with specific amino acid sequences (e.g., PEP7, PEP71, PEP74) that exhibit significantly higher reactivity to BMP-specific receptors, such as BMPR-IA and BMPR-II, by replacing certain amino acids in existing sequences, and their chemical introduction onto implant surfaces using linkers and matrices to enhance osteoblastic differentiation and calcification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If growth factors such as TGF-β, IGF-1 or BMP are coated on the implant surface before surgery, then osteointegration and osteogenesis abilities are enhanced, but the induction period becomes prolonged and treatment costs increase

Engineering Contradiction:
Improveosteointegration abilityVSAvoidinduction period
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent modifies the amino acid sequence parameters of oligopeptides to create variants with improved binding affinity to BMP receptors. By changing specific amino acid residues in the oligopeptide structure, the patent achieves enhanced receptor interaction efficiency, thereby reducing the induction period while maintaining reliable osteointegration

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates simplified copies of BMP-derived peptides with optimized sequences that replicate and enhance the natural bone morphogenetic protein's ability to bind to BMP receptors. These synthetic oligopeptide copies are more efficient than the original BMP molecules, achieving faster osteointegration without requiring large amounts of expensive growth factors

Inventive Principle:
Principle #26Copying

2Reliability

If large amounts of physiologically active substances are used for coating, then osteointegration ability is improved, but the substances cannot effectively remain at the implanted site and application range is restricted

Engineering Contradiction:
Improveosteointegration abilityVSAvoidactive substance retention
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent extracts and utilizes only the essential amino acid sequence motifs from BMP molecules that are responsible for receptor binding activity. By isolating these critical functional segments into short oligopeptides, the patent eliminates the need for large amounts of full-length growth factors, reducing substance loss while maintaining effective osteointegration capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent concentrates the bioactive functionality into specific local regions of the oligopeptide structure, particularly at the amino acid sequences that directly interact with BMP receptors. This localized functional design ensures that the active substance remains effective at the implant site without requiring widespread distribution or large quantities

Inventive Principle:
Principle #3Local quality

3Ease of manufacture

If coating is conducted at extremely limited area, then application is simplified, but effective osteogenesis cannot be achieved over the whole surface of implant

Engineering Contradiction:
Improvecoating applicationVSAvoidosteogenesis coverage
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent develops oligopeptides with universal binding capability that can interact effectively with BMP receptors across the entire implant surface. The optimized amino acid sequences provide multi-functional activity, enabling complete surface coverage with uniform osteogenesis promotion, eliminating the limitation of restricted application areas while maintaining manufacturing simplicity

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 new oligopeptides demonstrate improved binding affinity to BMP-specific receptors, significantly shortening the osteointegration period, increasing the success rate of implant surgeries, and inducing osteogenesis without the need for bone fillers, even in patients with poor bone quality.

Implementation Method 1

BMPs interact with BMP receptors (BMPRs) on the cell surface to initiate intracellular signal transduction

Methodology Applied
Scientific EffectLigand binding:

Implementation Method 2

inducing cross-phosphorylation from the type II receptor to the type I receptor, activating the Smad signaling cascade

Methodology Applied
Scientific EffectSignal transduction:

Implementation Method 3

inducing cross-phosphorylation from the type II receptor to the type I receptor

Methodology Applied
Scientific EffectPhosphorylation:

Implementation Method 4

chemical introduction onto implant surfaces using linkers and matrices

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Data Source

PatentEP2540739B1Oligopeptide improving differentiation of osteoblasts
Publication Date: 2015.10.14 OSSTEMIMPLANT CO LTD
  • EP2540739B1 patent drawingFigure 1
  • EP2540739B1 patent drawingFigure 2
  • EP2540739B1 patent drawingFigure 3

AI summary

The present invention relates to oligopeptides applicable to a dental implant, which are selected from the group consisting of PEP7 (SEQ ID No. 1), PEP71 (SEQ ID No. 2), EP72 (SEQ ID No. 3), PEP73 (SEQ ID No. 4), PEP74 (SEQ ID No. 5), PEP75 (SEQ ID No. 6) and PEP76 (SEQ ID No. 7). The oligopeptides of the present invention have very high reactivity for a BMP-specific receptor to increase osteoblastic differentiation and calcification, thereby showing improved osteointegration and osteogenesis.