1. Biomimetic Peptide Coating on Bioresorbable Magnesium Metal
A. Patil (Pitt), C. Sfeir (Pitt) E. Beniash (Pitt)
Fig 1 is not labeled
Corrosion is not a disadvantage, this is why Mg was chosen as a resorbable material, I have rephrased the sentence in fundamental questions/challenges
In the results, can you place the amino acid frequency for 23 biopanning against WX41 into Figure 2 to show the alloy specificity.
Also in the summary you mention a number of unique properties. Please list them in the bottom of left collumn, i.e. hydrophobicity, charge, lack of negatively charged AAs et cetera, see the progress report for 99.9% Mg and look at the Selected peptides against WX41
Surface Morphology of Peptide Coated Mg Surface
SEM study confirms the peptide coating is fairly homogeneous and thin. The surface topography of the coated discs was smoother than of bare Mg discs. Surface features are muted due to the peptide coating
Project Goals
The aim of this study was to develop high affinity synthetic peptide coating for an orthopedic fixation device made of Mg using Phage Display Technology to control the corrosion rate and increase its biocompatibility A B
Target Surface
Linker Peptide
Osteogenic Peptide
Figure 1 Schematic of peptide coating on a target surface
The Project’s Support of Strategic Plan
One of the goals of ES1 of the ERC “Revolutionizing Metallic Biomaterials” is to achieve corrosion control of Mg based alloys using various approaches. In this project, we propose to create biomimetic coating onto the Mg alloys surface to control its corrosion rate of an orthopedic fixation device.
Figure 3 SEM images of Mg surface without (A) and with (B) peptide coating
Mg Corrosion Rate Study
The corrosion study demonstrated that both peptides have significantly slowed the rate of corrosion, when compared to the control
Fundamental Questions/Challenges
Magnesium (Mg) and its alloys are currently being investigated as resorbable orthopedic implant material. Mg has excellent biocompatibility, light weight and density matching to bone. However it is necessary to control the rate of corrosion to prevent forming hydrogen pockets at the implantation site and to match the resorption and regeneration rates. Currently different coating strategies have been used to control the corrosion rate of Mg and its alloys. Among many strategies, bioactive high affinity peptide coating of to resorbable Mg alloys is a promising method.
One of the fundamental questions/ challenges here is to develop the coatings for highly unstable corroding Mg alloy surfaces. We have phage display selection strategies identify high affinity peptide sequences to overcome this problem. The next step in our peptide design is to select osteoinductive signaling peptides and designing a hybrid peptide ass shown in Fig 1.
Figure 4 A) Schema of the H2 evolution experiment, B) Plot showing H2 release over time as a measure of Mg corrosion kinetics (n=3, mean ± SE)
Summary of Achievements
The first round of biopanning experiments against Mg and its alloy (WX41 & AZ31) surfaces have been completed and our sequence analysis has revealed a number of unique features of these sequences.
Homogenous thin layer of peptide coating can be created on Mg and its alloys surfaces.
Demonstrated that these peptides can regulate the rate of Mg metal corrosion.
Currently starting in vivo studies to test biocompatibility and corrosion control properties of the selected peptides
We anticipate that this work will lead to development of biomimetic coating layers for resorbable orthopedic implant devices
Year 5 Research Results
Mg Biopanning Experiments with 99.9% Pure Mg
Our analysis of Mg- selected sequences show threefold increase in Pro frequency in comparison to naïve Ph.D. 7 library, indicating a strong selection for this amino acid in the peptides binding to Mg surface. Compared to the naïve library, the 99.9% Mg selected peptides lacked negatively charged amino acids Asp and Glu, but were rich in Pro and contained more hydrophobic amino acids such as Leu, Ile, Val and Tyr (Figure 2). In case of WX41 alloy selected sequences, high frequency of Asp (D) is observed, which was absent in the 99.9% Mg selected sequences.
Future Research Plans
Years
Design, synthesis and characterization of Mg-alloys binding peptides
Tissue culture test for biocompatibility and osteogenic properties
Selection, synthesis and design of bio-inspired peptides with osteogenic properties: SSD3, SSD5 with and without RGD motif, BMP2 active domain KIPKASSVPTELSAISTLYL
In-vivo subcutaneous testing of Mg-alloy discs coated with selected peptides
MicroCT, histology and chemical analyses of the implants
In vivo testing of the Mg fixation plates coated with selected peptides
MicroCT, histology and chemical analyses of the implants
Relationships between main aims and the timetable of the project
Figure 2 Frequencies of AA occurrence in peptide sequences (%)
ES1: Craniofacial and Orthopedic Applications