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Crystal Structures Comprising Elastin-Like Peptides

a crystal structure and peptide technology, applied in the direction of peptide/protein ingredients, crystal growth process, polycrystalline material growth, etc., can solve the problems of lack of appropriate alternatives, lack of regenerative capacity of mature enamel, and lack of functional highly organized materials for dental applications, etc., to achieve low bone density or osteoporosis

Inactive Publication Date: 2019-05-09
MINTECH V LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a new hybrid organic-inorganic system based on protein scaffold membranes that can grow hierarchically-ordered apatite crystalline structures that resemble those found in natural dental enamel. The invention also provides a process for producing these crystals, as well as a method for tuning or controlling the directionality of crystal growth. The synthetic crystals can be used for medicine, including for the prevention and treatment of dental and bone diseases. The invention also includes the use of the synthetic crystals in the preparation of medical implants such as dental and bone implants.

Problems solved by technology

Unlike dentine and bone, mature enamel has no regenerative capacity or appropriate alternatives due to the complexity to create materials that mimic its unique structure (White, S. N. et al.
Nevertheless, none of these previous attempts have successfully recreated the highly organized mineralized apatite structure across multiple length-scales found in natural enamel, which evidences the current absence of a functional highly organized material for dental applications.

Method used

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  • Crystal Structures Comprising Elastin-Like Peptides
  • Crystal Structures Comprising Elastin-Like Peptides
  • Crystal Structures Comprising Elastin-Like Peptides

Examples

Experimental program
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example 1

Discussion and Results

Example 1

Discussion and Results

[0244]Membranes were fabricated as detailed above using three different ELPs comprising a statherin-derived peptide (SN), RGDS, or no bioactive segment (IK), where the only molecular difference is the presence of the bioactive sequence (Table 2). SN membranes have been shown to enhance mineralisation and therefore were used as the main experimental group in this study, while RGDS membranes were used for comparison, and IK membranes and borosilicate glass substrates coated with the different ELP molecules were used as controls. Surprisingly, upon incubation in a supersaturated solution rich in Ca2+, PO43−, and F− (10, 6, and 2 mM, respectively) at near physiological conditions (37° C. and pH 6.0), distinctive hierarchically mineralized structures (FIG. 30a-c) were observed on both sides of the SN and IK membranes (FIG. 30b) and not on the ELP-coated glass surfaces, which only showed flat platelet-like crystals (FIG. 35a-d). The res...

example 2

Micro-Fabricated ELP-Based Membranes

[0255]Method

[0256]Direct write laser lithograpy was used to fabricate a silicon chrome photomask. A (111)-oriented silicon wafer was coated with an 8 um thick layer of SU8-10 photoresist, soft baked (65 C for 2 minutes and 950 C for 5 minutes), and then exposed through the silicon chrome photomask (30 mWcm-2 for 3.3 seconds). It was subsequently post-exposure baked (65 C for 1 min and 950 C for 5 min) and developed using SU8 developer for 30 s. Topographies were transferred to polydimethylsiloxane (PDMS) using a standard soft lithography process. The PDMS prepolymer was poured on top of the patterned master, degassed under vacuum for 7 min, and then cured at 650 C for 2 hours. The resulting topographically patterned mold was subsequently used to create membranes with the different structural components using similar dropcasting method as mentioned for the smooth membranes.

[0257]Results

[0258]FIG. 14 shows the preferential nucleation and growth of f...

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Abstract

The present invention relates to new biomimetic mineralized apatite structures. The present invention also relates to processes for the production of new biomimetic mineralized apatite structures based on natural and synthetic protein scaffolds. In particular, the invention provides synthetic crystal having a hierarchical structure formed on an elastin-like polypeptide membrane or hydrogel. The invention also provides methods of making such crystals, both in vivo and in vitro, as well as kits comprising membranes or hydrogels with cross-linking agents and / or mineralization solutions. The invention also provides the use of such structures in methods of treatment.

Description

FIELD OF THE INVENTION[0001]The present invention relates to new biomimetic mineralized apatite structures. The present invention also relates to processes for the production of new biomimetic mineralized apatite structures based on natural and synthetic protein scaffolds.BACKGROUND TO THE INVENTION[0002]Nature is rich with examples of sophisticated materials displaying outstanding properties that emerge from their specific hierarchical structure. Dental enamel has a distinctive hierarchical organization that generates its remarkable toughness, wear resistance, and critical role in tooth function (Boyde, A. Microstructure of enamel. CIBA Foundation Symposia, 18-31 (1997). At the molecular level, enamel is 97% by weight carbonated hydroxyapatite (HAp) (the rest being organic matrix and water) (Elliott, J. C. Structure, crystal chemistry and density of enamel apatites. CIBA Foundation Symposia, 54-72 (1997)) with different ionic substitutions in the lattice according to location (Robi...

Claims

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Application Information

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IPC IPC(8): C07K14/78C30B29/58C30B7/04
CPCC07K14/78C30B29/58C30B7/04A61K38/00
Inventor ELSHARKAWY, SHERIF AHMED ABDELSALAMAL-JAWAD, MAISOONCHAVARRIA, ALVARO MATATEJEDA-MONTES, ESTHERSANCHEZ, ROXANNA SHARON RAMNARINE
Owner MINTECH V LLC