Technology

Conjugations of catechol or gallol to a biocompatible polymer library result in a new adhesive library,
which is referred to be BiMM (Bio-inspired Medical Materials) library at InnoTherapy.
InnoTherapy technology is originated from nature. Among numerous extraordinary phenomena in nature, the adhesive materials found in nature are the focus of research and commercialization at InnoTherapy. Because over 70% of the human body weight is composed of water, the property of underwater adhesion is essential for effective medical adhesives. Thus, at InnoTherapy, we wondered how underwater organisms could adhere to the surface and went on to study the mechanism of binding between compounds and molecules essential in such phenomenon. By applying the findings, we have developed medical devices with outstanding adhesive abilities.
So far, the material essential in underwater adhesion has been known to be polyphenol molecule such as catechol or catecholamine. InnoTherapy has conducted various basic and applied studies in relation to these molecules. 1) 2) 3) In addition, underwater organisms show a system of adhesion using calcium-based cement. Nevertheless, at InnoTherapy, adhesive materials based on polymeric biomaterials were the focus of development through which catechol or catecholamine was introduced to various biocompatible polymers.
catechol

Besides catechol, the property of underwater adhesion has been exhibited by another compound called gallol. It is a substance mainly found in plants and is responsible for astringent taste. Adhesion and the astringent taste are intimately related, as gallol-containing substances adhere to oral mucosa to increase frictional force. Using this property, gallol can be applied in a device to deliver a drug by adhering to the mucosa of the oral cavity as well as the digestive organs.

A common, representative characteristic in the materials in BiMM library is that they form robust complexes
by binding with proteins in body fluid. Based on this, an innovative medical device can be created.
Hemostatic agents can be prepared based on the property of binding with plasma proteins in the blood. It is particularly useful as alternative hemostatic materials for patients with anticoagulant drugs such as aspirin and warfarin due to chronic cardiovascular disease, diabetes, or hemostatic disorder with difficulty of hemostasis caused by a genetic factor. 4)5)
An effective device to prevent mucosal bleeding in digestive organs can be produced based on the property of binding with mucosal proteins. 6) 7) 8)
A self-sealing, complete hemostasis technology is developed by coating the BiMM library polymers onto surfaces of syringe needles or other narrow diameter 1D devices. 9)
Nanoparticles can be produced based on binding with proteins and peptides as drug candidates.10) Such formulation is a highly suitable method for drug delivery.

The surface of viral vectors used in gene delivery is composed of proteins. Thus, a stabilized formulation for delivering the therapeutic gene to the target organ can be extended to the platform applicable in gene therapy.

The novel technologies at InnoTherapy described so far as well as those unmentioned will be expanded to  
a diversity of fields to promote the path towards the Medical Transcender.

References

  1. Lee H, Scherer NF, Messersmith PB. Single-molecule mechanics of mussel adhesion. Proc Natl Acad Sci USA. 2006;103(35):12999-13003. doi:10.1073/pnas.0605552103 null
  2.  Lee H, Lee BP, Messersmith PB. A reversible wet/dry adhesive inspired by mussels and geckos. Nature. 2007;448(7151):338-341. doi:10.1038/nature05968 null
  3.  Lee H, Dellatore SM, Miller WM, Messersmith PB. Mussel-inspired surface chemistry for multifunctional coatings. Science. 2007;318(5849):426-430. doi:10.1126/science.1147241 null
  4. Ryu JH, Lee Y, Kong WH, Kim TG, Park TG, Lee H. Catechol-functionalized chitosan/pluronic hydrogels for tissue adhesives and hemostatic materials. Biomacromolecules. 2011;12(7):2653-2659. doi:10.1021/bm200464x null
  5. Shin M, Ryu JH, Kim K, Kim MJ, Jo S, Lee MS, Lee DY, Lee H. Hemostatic swabs containing polydopamine-like catecholamine chitosan-catechol for normal and coagulopathic animal models. ACS Biomater Sci & Eng. 2018; 4(7):2314-2318. doi:10.1021/acsbiomaterials.8b00451 null
  6. Ryu JH, Choi JS, Park E, Eom MR, Jo S, Lee MS, Kwon SK, Lee H. Chitosan oral patches inspired by mussel adhesion. J Control Release. 2020;317:57-66. doi:10.1016/j.jconrel.2019.11.006 null
  7. Kim K, Shin M, Koh M-Y, Ryu JH, Lee MS, Hong S, Lee H. TAPE: a medical adhesive inspired by a ubiquitous compound in plants. Adv Funct Mater. 2015;25(16):2402-2410. doi: 10.1002/adfm.201500034 null
  8. Kim K, Kim K, Ryu JH, Lee H. Chitosan-catechol: a polymer with long-lasting mucoadhesive properties. Biomaterials. 2015;52:161-170. doi:10.1016/j.biomaterials.2015.02.010 null
  9. Shin M, Park SG, Oh BC, Kim K, Jo S, Lee MS, Oh SS, Hong S-H, Shin E-C, Kim K-S, Kang S-W, Lee H. Complete prevention of blood loss with self-sealing haemostatic needles. Nat Mater. 2017;16(1):147-152. doi:10.1038/nmat4758 null
  10. Shin M, Lee HA, Lee M, Shin Y, Song J-J, Kang S-W, Nam D-H, Jeon EJ, Cho M, Do MJ, Park SH, Lee MS, Jang J-H, Cho S-W, Kim K-S, Lee H. Targeting protein and peptide therapeutics to the heart via tannic acid modification. Nat Biomed Eng. 2018;2(5):304-317. doi:10.1038/s41551-018-0227-9 null