Biomedical Polymers 1o1065

BIOMEDICAL POLYMERS B.Sc. Project Report

by

PAULAMI BOSE Roll No: D10/CH-012

DEPARTMENT OF CHEMISTRY RAVENSHAW UNIVERSITY CUTTACK

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BIOMEDICAL POLYMERS A Project report Submitted for the Partial Fulfillment of the

DEGREE OF BACHELOR OF SCIENCE in

CHEMISTRY

Submitted By

PAULAMI BOSE

Under the supervision of DR. TUNGABIDYA MAHARANA

DEPARTMENT OF CHEMISTRY RAVENSHAW UNIVERSITY CUTTACK

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DEPARTMENT OF CHEMISTRY RAVENSHAW UNIVERSITY, CUTTACK

CANDIDATE’S DECLARATION

I hereby certify that the work which is being presented in the report entitled “BIOMEDICAL POLYMERS” in partial fulfillment of the requirements for the award of the Bachelor of Science and submitted in the Department of Chemistry of the Ravenshaw University, Cuttack is an authentic record of my own work carried out under the supervision of Dr. Tungabidya Maharana, Lecturer, Department of Chemistry, Ravenshaw University, Cuttack The matter presented in the report has not been submitted by me for the award of any other degree of this or any other Institute.

(PAULAMI BOSE)

This is to certify that the above statement made by the candidate is correct to the best of my (our) knowledge.

(Dr. TUNGABIDYA MAHARANA) Supervisor

(Dr. SMRUTI PRAVA DAS) HoD Chemistry

Date:

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ACKNOWLEDGEMENTS

I, hereby acknowledge that the project entitled ‘BIOMEDICAL POLYMER’ is done under the supervised guidance of Dr. Tungabidya Maharana, Dept. of Chemistry, Ravenshaw University. I would also like to thank Dr. Smruti Prava Das, HoD Chemistry, Dr. Alekh Kumar Sutar and other faculties of the Dept. of Chemistry for their and valuable time in developing this project. Last but not the least I would also like thank my parents, family and friends for their constant .

(PAULAMI BOSE)

Department of Chemistry, Ravenshaw University, Cuttack

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Contents Page No. 1. What are Biomedical Polymers…????

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2. Types of Biomedical Polymers

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2.1. Non-Biodegradable Polymers

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2.2. Biodegradable Polymers

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3. Images of Biomedical Polymers

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4. Applications of Biomedical Polymers

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4.1.

Medical Applications of Bioabsorbable Polymers

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4.2.

Applications in Human Body

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5. Advantages and Disadvantages of Biomedical Polymer

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6. Future prospects of Biomedical Polymers

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7. Conclusion

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References

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1.

WHAT ARE BIOMEDICAL POLYMERS….???

Polymer scientists, working closely with those in the device and medical fields, have made tremendous advances over the past 30 years in the use of synthetic materials in the body. A variety of polymers have been used for medical care including preventive medicine, clinical inspections, and surgical treatments of diseases. Among the polymers employed for such medical purposes, a specified group of polymers are called polymeric biomaterials when they are used in direct with living cells of our body. Medical practitioners today often seek to cure ailments or improve a patient’s quality of life by replacing a defective body part with a substitute. But until quite recently, physicians were limited to using off-the-shelf supplies that weren’t designed for the application. Motivated by a need for custom-made materials for specific medical applications, materials scientists, chemists, Chemical engineers, and researchers in other disciplines have turned their attention to creating high-performance biomaterials. Among the new crop of substances are novel biodegradable polymers and modified natural substances designed for use in a wide range of implantable applications including orthopedic and dental devices, drug-delivery systems, tissue engineering scaffolds, and other uses. Minimum requirements of Biomaterials: 1.

Non-toxic (biosafe) They should be non-pyrogenic, Non-hemolytic, Chronically non-inflammative, Non-allergenic, Non-carcinogenic, Non-teratogenic, etc..

2. Effective They should be effective functionally, should have good performance, durability,etc. 3. Sterilizable They can be sterilizable by using Ethylene oxide, γ-Irradiation, Electron beams, Autoclave, Dry heating, etc 4. Biocompatible The most important one, for the use of any material in human body they should be biocompatible interfacially, mechanically, and Biologically.

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A Thermoresponsive polymer is a polymer which undergoes a physical change in the presence of external thermal stimuli. The ability to undergo such changes under easily controlled conditions puts this class of polymers into the category of smart materials. Thermoresponsive polymers can be used for various biomedical applications including drug delivery, tissue engineering and biofunctional molecular techniques for smarter behavior. Many developments have paved the way for ready-to-use applications using the fast and pronounced phase transition of poly(N-isopropylacrylamide) (PNIPAAm).

Graft polymers (e.g. Poly amino acids) are branched copolymers where side chain is structurally different from the main chain. In the above figure, graft polymer bearing hydrophobic and hydrophilic chains undergo self-aggregation which in aqueous medium at proper concentration (Critical Aggregation Concentration) forms colloidal micelle systems having hydrophobic core and hydrophilic shell. Then these active molecules can be physically or chemically linked to the other amphiphilic copolymers. Now the dissolution process or hydrolysis allows the release of active substances and that can be tested with drugs.

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2.

TYPES OF BIOMEDICAL POYMERS

BIOMEDICAL POLYMERS

NON-BIODEGRADABLE POLYMER

BIODEGRADABLE POLYMER

Examples: Biodegradable Polymers • Polyglycolic acid (polyglycolide)

Non-Biodegradable Polymers • Polyethylene terephthalate (PET), Dacron

• Polylactic acid (polylactide)

• Nylon 6,6

• Poly-3-hydroxybutyrate

• Polyurethanes

• Polydioxanone

• Polytetrafluoroethylene (PTFE)

• Linear polyaliphatic esters

• Polyethylene (low density and high density) plus UHMW • Polysiloxanes (silicones) • Poly(methylmethacrylate)

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2.1. •

NON-BIODEGRADABLE POLYMERS

Biomedical polymers with high molecular weight that do not degrade in the body can be classified as Bioinert or Non-Biodegradable Polymers.

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Most problems that occur with the non-degradable polymers are when used for medical applications are due to leaching of plasticisers and additives.

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It is important to characterise the grade of the polymer in use. What is sold as polymer X by one manufacturer may be very different from polymer X sold by another due to the difference in purity and additives present.

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Surface reactions and absorption of proteins can cause problems when non-degradable polymers are used in human body as a permanent substitute for various medical/surgical reasons.

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Surface texture and form of the polymer are important considerations when used as an implant in human body.

Polyethylene Oxide (PEO) star molecules are used to terminate biomedical polymers. PEO surface modifies the end groups and forms a protective layer over the base polymer.

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2.2

BIODEGRADABLE POLYMERS

Many opportunities exist for the application of synthetic biodegradable polymers in the biomedical area particularly in the fields of tissue engineering and controlled drug delivery. Degradation is important in biomedicine for many reasons. Degradation of the polymeric implant means surgical intervention may not be required in order to remove the implant at the end of its functional life, eliminating the need for a second surgery. In tissue engineering, biodegradable polymers can be designed such to approximate tissues, providing a polymer scaffold that can withstand mechanical stresses, provide a suitable surface for cell attachment and growth, and degrade at a rate that allows the load to be transferred to the new tissue. Polymer degradation takes place mostly through scission of the main chains or side-chains of polymer molecules, induced by their thermal activation, oxidation, photolysis, radiolysis, or hydrolysis. Some polymers undergo degradation in biological environments when living cells or microorganisms are present around the polymers. Such environments include soils, seas, rivers, and lakes on the earth as well as the body of human beings and animals. Biodegradable polymers are defined as those which are degraded in these biological environments not through thermal oxidation, photolysis, or radiolysis but through enzymatic or non-enzymatic hydrolysis. When investigating the selection of the polymer for biomedical applications, important criteria to consider are; •

The mechanical properties must match the application and remain sufficiently strong until the surrounding tissue has healed.

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The degradation time must match the time required.

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It does not invoke a toxic response.

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It is metabolized in the body after fulfilling its purpose.

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It is easily processable in the final product form with an acceptable shelf life and easily sterilized.

Mechanical performance of a biodegradable polymer depends on various factors which include monomer selection, initiator selection, process conditions and the presence of additives. These factors influence the polymers crystallinity, melt and glass transition 3

temperatures and molecular weight. Each of these factors needs to be assessed on how they affect the biodegradation of the polymer. Biodegradation can be accomplished by synthesizing polymers with hydrolytically unstable linkages in the backbone. This is commonly achieved by the use of chemical functional groups such as esters, anhydrides, orthoesters and amides. Once implanted, a biodegradable device should maintain its mechanical properties until it is no longer needed and then be absorbed by the body leaving no trace. The backbone of the polymer is hydrolytically unstable. That is, the polymer is unstable in a water based environment. This is the prevailing mechanism for the polymers degradation. This occurs in two stages: •

Water penetrates the bulk of the device, attacking the chemical bonds in the amorphous phase and converting long polymer chains into shorter water-soluble fragments. This causes a reduction in molecular weight without the loss of physical properties as the polymer is still held together by the crystalline regions. Water penetrates the device leading to metabolization of the fragments and bulk erosion.

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Surface erosion of the polymer occurs when the rate at which the water penetrating the device is slower than the rate of conversion of the polymer into water soluble materials. Biomedical engineers can tailor a polymer to slowly degrade and transfer stress at the appropriate rate to surrounding tissues as they heal by balancing the chemical stability of the polymer backbone, the geometry of the device, and the presence of catalysts, additives or plasticisers. Polylactides, especially polyglycolide, are readily hydrolyzed in our body to the respective monomers and oligomers that are soluble in aqueous media. As a result, the whole mass of the polymers disappears, leaving no trace of remnants.

Generally, such a polymer that loses its weight over time in the living body is called an absorbable, resorbable, or bioabsorbable polymer as well as a biodegradable polymer, regardless of its degradation mode.

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Working Principle: Polymer is taken and shaped as needed, then seeded with living cells and bathed with growth factors. Now the cell multiplies to fill up the scaffold and grows into three- dimensional tissue. Once implanted in the body cells recreate their tissue function followed by blood vessels attaching themselves. Then the scaffold dissolves and blends with the surroundings. Specific applications of biodegradable polymers include : •

Sutures

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Dental devices

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Orthopedic fixation devices

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Tissue engineering scaffolds

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Biodegradable vascular stents

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3.

IMAGES OF BIOMEDICAL POLYMERS

Commercial Sutures

Braided Polyester

Multifilament Nylon

Schematic Diagram of an Artificial Kidney (HOMODIALYSIS)

Schematic Diagram of a Ventricular Assist Device

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PTFE

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APPLICATIONS OF BIOMEDICAL POLYMERS Polymer

Applications

Polymer

Applications

PDMS

Catheters Heart Valves

Polytetrafluoroethylene

Heart valves Vascular grafts Nerve repair

Polyurethane

Ventricular assist devices

Polyethylene

Catheters, hip, Prostheses

PGA, PLA and PLGA

Drug delivery devices

Polymethylmethacrylate (PMMA)

Fracture fixation

Cellophane

Dialysis membranes

4.1.

MEDICAL APPLICATIONS OF BIOABSORBALE POLYMERS Function

Purpose

Bonding

Closure Separ ation

Suturing

Vascular and intestinal anastomosis

Fixation

Fractured bone fixation

Adhesion

Surgical adhesion

Covering

Wound cover, Local hemostasis

Occlusion

Vascular embolization

Isolation

Organ protection

inhibition Scaffol d

Cellular proliferation Tissue guide

Capsulation

4.2.

Examples

Controlled drug Delivery

APPLICATIONS IN HUMAN BODY

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Adhesion prevention Skin reconstruction, Blood vessel reconstruction Nerve reunion Sustained drug release

5.

ADVANTAGES AND DISADVANTAGES OF BIOMEDICAL POLYMERS Advantages:

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Biomedical polymers are used for a variety of reasons, but the most basic begins with the physician's simple desire: to have a device, which can be used as an implant and will not necessitate a second surgical event for removal. In addition to not requiring a second surgery, the biodegradation may offer other advantages.

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Another exciting application for which biodegradable polymers offer tremendous potential is the basis for drug delivery, either as a drug delivery system alone or in conjunction to functioning as a medical device.

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The other reason for biodegradable polymers attracting much attention is that nobody will want to carry foreign materials in the body as long-term implants, because one cannot deny a risk of infection eventually caused by the implants.

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Costly procedures have now been given new lower cost alternatives.

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Polymers will continue to improve medicine and if the first fifty years of development is any indication, the next fifty years will serve to save many lives and help to make procedures and applications safer and more efficient

Disadvantages: •

Biocompatibility is highly desirable but not indispensable; most of the clinically used biomaterials lack excellent biocompatibility, although many efforts have been devoted to the development of biocompatible materials by biomaterials scientists and engineers.

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A large unsolved problem of biomaterials is this lack of biocompatibility, especially when they are used not temporarily but permanently as implants in our body.

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Low effectiveness is another problem of currently used biomaterials.

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6.

FUTURE PROSPECTS FOR BIOMEDICAL POLYMERS •

Recently researches are been carried out for the development of biomaterials with surface modification techniques for the incorporation of low surface energy fluorocarbon containing surface modifying and bioactive agents.

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There is a need for tailoring the composition of polyurethanes for the study of mechanisms of biodegradation and modeling the biodegradation processes of materials.

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There is a need for an extensive study on key mechanisms involved in saliva and bacteria interactions with Dental composites.

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Extensive study is still been carried out on the biodegradation of composites and bonding of restorative resins to teeth/material interfaces.

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Research is in progress for the use of degradable polymers with porous calcium polyphosphates for soft connective tissue-to-bone attachment and also on degradable polymers for orthopaedic tissue regeneration applications.

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Need for the detailed analysis of material blood compatibility by protein adsorption, enzyme assays and platelet adhesion.

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Still there is need for the development of antimicrobial materials for implantable medical devices and also for the development of biodegradable vascular graft materials.

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7.

CONCLUSION Indeed, biomaterials have already made a huge impact on medical practices. But, the opportunities that lie ahead of us are enormous. “Tissue engineering and related subjects have the potential to change paradigms” for treating diseases that today cannot be treated effectively like certain forms of liver failure, paralysis, and certain disorders. “Clearly we are faced with big challenges “. But, the message I try to get across to everyone mostly to young students like us is that the field holds a tremendous promise. We expect that in the future, more and more surgeries will be available using biodegradable products that will speed up patient recovery and eliminate follow-up surgeries.

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REFERENCES 1.

Biomaterials, Artificial Organs and Tissue Engineering by Dr Robert Hill, Imperial College, London.

2.

Biodegradable plastics a year in review (http:/ / www. ia. ca/ anti-litter/ pdf/ BIODEGRADEABLE POLYMERS (A REVIEW 24 Nov. 2000. Final. PDF), Environment and Plastics Industry Council.

3.

Synthetic biodegradable polymer. Source: http://en.wikipedia.org/w/index.php?oldid=433261600

4.

Fried, J. R., “Polymer Science and Technology.”, Prentice Hall, New Jersey 1995

5.

“Dialysis and the Artificial Kidney”, “Polyurethane – Features and Benefits”, www.elastchem-ca.com/poly.html

6.

“Polyurethane – Features and Benefits”, www.elastchem-ca.com/poly.html

7.

Y. Ikada, “Interfacial Biocompatibility”, in: “Polymers of Biological and Biomedical Significance”, ACS Symp. Ser., S. W. Shalaby, Y. Ikada, R. Lander, J. Williams,Eds.

8.

Gilding DK, and Reed AM, "Biodegradable Polymers for Use in Surgery— Polyglycolic/Poly(lactic acid) Homo- and Copolymers," Polymer.

9.

Middleton, John C. and Tipton, Arthur J. (March 1998) Synthetic Biodegradable Polymers as Medical Devices (http:/ / www. mddionline.com/ article/ syntheticbiodegradable-polymers-medical-devices), Medical Plastics and Biomaterials Magazine.

10.

Andreadis, S., “Polymer in Medicines”, Tissue engineering handout, February 2001, University at Buffalo.

11. Barrows TH. Degradable implant materials: a review of synthetic absorbable polymers and their applications. Clin Mater

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