Designing Cell-Compatible Hydrogels for Biomedical Applications

1. Designing Cell-Compatible Hydrogels for Biomedical Applications GROUP 6 Anthony SchellerLameesElnihum Kyle Belleville Michael Li Colorful hydrogels! http://cdn.arstechnica.net/wp-content/uploads/2012/06/hydrogels.jpg

2. Abstract The many uses of hydrogels! • Hydrogels can influence the cell behavior and its biochemical and biophysical processes • Hydrogels can influence cell behavior by mimicking the extracellular matrix • Hydrogels will provide new and improved methods of regenerative medicine, biotechnology, pharmacology, and biosensors in the near future  http://sticky.kaist.ac.kr/menu2/menu3.php

3. Introduction Can hold many times there weight and flexible! • Hydrogels • Polymer chains that are typically hydrophilic, usually highly absorbent and very flexible • Hold potential in biomedical field due to water-carrying capacity • Can hold up to 600x their weight in water! www.stevespanglerscience.com  Can be used in contact lenses • Numerous applications • Stem Cells • Tissue Engineering • Cell Therapy • Contact Lenses • Cancer Treatment www.meyevisionkaty.com 

4. Introduction • From Left to Right: Polymer powder; polymer powder added to a drop of water; hydrogel (after cross-linkage); dehydrated hydrogel (retains overall shape); sesame seed shown for scale http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428

5. Introduction • Water-borne microgels in suspension containing several immobilized molecules – highlights possibilities for injectablehydrogel drug delivery http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428

6. Introduction • “Gel-in-gel” experiment: Hydrogels can be tested to determine if they are sustainable inside other hydrogels http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428

7. Introduction • A microgel containing fluorescently labeled cells – highlights potential uses in cell delivery for tissue regeneration http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428

8. Introduction • Encapsulated fibroblast cells – for studying cell behavior; may advance cancer and stem cell research http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428

9. Basic Concepts/Principles • Hydrogels applicable in the biological and medical fields • Hydrogels mimic the extracellular matrix, which naturally provides structural support in a cell & contains human proteins and other fibers Above: Diagram of the extracellular matrix in which the hydrogelmust be able to survive http://cdn.arstechnica.net/wp-content/uploads/2010/01/clay_hydrogel.jpg

10. Basic Concepts/Principles • We can design hydrogels to have specific functions in the body: • Achieve specific interactions between hydrogels and the human body • Typically semi-synthetic hydrogels to allow for natural proteins to help news.uns.purdue.edu Research is currently being done to try to develop human- compatible hydrogels at Purdue University

11. Basic Concepts • Is the hydrogel compatible with the body? • Specific molecular interactions at the cell-material interface • In the 1990’s, natural proteins were used to create a hybrid structure that was able to control certain properties brought about by a synthetic constituent Hydrogels having molecular interactions on the top allows special properties such as ability to hold pigmentation as shown above http://www.pharmainfo.net/files/u4117/ud-hydrogels-20261.jpg

12. Basic Concepts • Research in the 1990’s has led to what we have today • Most notably polyethylene glycol mimicking collagenase substrates found in natural proteins • Polyethylene glycol can act as a collagenase substrate found in extracellular matrix proteins • An advantage of this is that they are very strong and elastic allowing for high chances of survival in the body Polyethylene Glycol structure and the bottle below of polyethylene glycol allows for numerous advantageous properties www.drugfuture.com

13. Basic Concepts C: Self-assembled hydrogel is more automatic for the cell to converge to a practical structure for the any particular environment B: Porous Hydrogel allows for permeability of objects such as nutrients to flow A: Dense Hydrogel Structure allows for protection from unwanted objects to seep through D: Fibrous hydrogel allows for structure in the cell. http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428 Center: fully hydrated hydrogel (blue) with encapsulated cell (brown)

14. “Work Performed” • Paper is a discussion on past projects that have and will help with future development, rather than an analysis of lab work data • More of a focus on development, application, and future research of hydrogels in a medical environment • Paper specifically mentions: • Degradation • Bioadhesion • Bioactiviy • Transport • Mechanical properties Hydrogel has many structural properties that allow for its utility http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428

15. Chemical properties that allow structural advantages of the hydrogel. All of the letters show the different types of bonds involved in the hydrogel. http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428

16. Biodegradation • Essential for applications that require a controlled absorption • Achieved by controlling the amount of hydrolytically liable cross-links in the polymer network • This results in more efficient tissue repair • Implants with oligopeptides that have facilitated a reabsorption rate that is relatively close to the normal repair timeline outperformed other material options Wound care products used for tissue repair http://jan.ucc.nau.edu/~daa/woundproducts/duoderm.jpg

17. Bioadhesion • Allows cells and tissues to adhere to other components in the body • Important in surgeries and tissue regeneration • Bioadhesive features can be engineered using linker molecules enabling covalent/non-covalent molecular interactions between the implant and surroundings • Above: example of studying bioadhesion: Experimentally straining a tissue, skin, muscle, & brain cell to observe and better understand their functions and determine how and what kind of new materials (such as hydrogels) can be made to aid them http://www.sciencemag.org/content/310/5751/1139/F1.large.jpg

18. Bioadhesion cont. • 3rd degree burn treatment: Hydrogels help grow new, scar-free skin http://nextbigfuture.com/2011/12/in-third-degree-burn-treatment-hydrogel.html

19. Bioactivity • Bioactivity in hydrogels is useful for materials that mediate specific biological events in the body based on: • Endogenous cell recruitment • Local morphogenesis • Controlled cell differentiation Illustration of process – Isolate cells from body; observe and apply experiments towards cells to better understand them; design new materials such as hydrogels to aid cell function/goal http://coledeforest.com/publications.html

20. Transport • Hydrogel porosity • Can regulate a therapeutic drug’s diffusion through the polymer network depending on the drug’s properties • Important in tissue engineering • Drug molecular size (relatively large or small?) • Hydrogel structure can be engineered to limit mobility and modulate release kinetics Injectable biomaterials (hydrogels) for tissue engineering http://ej.iop.org/images/1748-605X/7/2/024104/Full/bmm406403f3_online.jpg

21. Mechanical Properties • Convey important physical cues to cells by mediating: • Homeostasis • Morphogenesis • Cell growth • Contractility • Differentiation • Pathophysiology • Hydrogels’ toughness and flexibility can be engineered • Increase fracture stiffness vs. retaining water content Determining hydrogel stiffness based on tissue type http://www.excellness.com/background-en3.html

22. Conclusions • Paper laid out a path for future development • Good synthesis of past research papers that helped present the basic understandings of medical applications of hydrogels allowing for development • Discussed specifically how to accomplish future goals with specified attributes • Choosing hydrogels versus other methods based on desired goal http://www.tebu-bio.com/index.php?module=tech-info&id_cms=117&type_cms=3

23. http://www.innovent-jena.de/en/INNOVENT-/Departments/Biomaterials__185/http://www.innovent-jena.de/en/INNOVENT-/Departments/Biomaterials__185/ Hydrogels in a petri dish; synthesis of hydrogels for further testing Assessment • Improvements • Could have taken into account other properties the medical industry might need in a hydrogel • Discuss the possibility of expanding the use of hydrogels to appeal to a larger market and producing hydrogels on a larger scale • Go into detail of applications • Follow Up • Lots of future development leading to synthesizing hydrogels and testing them on lab animals, eventually leading to human applications • Analysis • Applications of hydrogels are broad • Tailoring hydrogels to personal specifications is important in medical industry

24. Further Suggestions • Discuss, other than the practical examples mentioned at the end of the paper, applications of hydrogels • Could use other sources to find out the potentials of tailored hydrogels and their specific uses • Discuss cost and feasibility of certain materials • Optimization of costs, economics http://www.futurity.org/science-technology/create-retinas-from-%E2%80%98jell-o%E2%80%99/ Colorful hydrogels A new way to create hydrogels has been developed by immobilizing different proteins at the same time.

25. References • Article citation: • Science, 1 June 2012: Vol. 336 no. 6085 pp. 1124-1128 • Article source: • http://www.sciencemag.org/content/336/6085/1124.full.pdf?sid=95c7472c-bef1-44cc-afed-e1144483d428 • Other sources: • http://arstechnica.com/science/2012/06/organic-hydrogel-outperforms-typical-carbon-supercapacitors/