Biomedical Polymers

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 rec record of my own work carrie ried out under the supervi rvisio sion of  Dr. Tungab Tungabidy idyaa Maharan Maharana, a, Lectur Lecturer, er, Depart Departmen mentt of Chemist Chemistry, ry, Ravensh Ravenshaw aw Univer University sity,, 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 candidate is correct 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 support 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 support. support.

(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 Types of Biomed Biomedical ical Polym Polymers ers

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2.1. Non-Biodegradable Polymers

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2.2. Biodegradable Polymers

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3. Im I mages 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 for such such medi medica call pu purp rpos oses es,, a spec specif ifie ied d grou group p of poly polyme mers rs are are call called ed poly polyme meri ricc biomaterials when they are used in direct contact with living cells of our body.

Medical Medical practitione practitioners rs today often seek to cure ailments or improve improve a patient’s patient’s quality 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 implantable application applicationss including including orthopedic orthopedic and dental devices, drug-deliv drug-delivery ery systems, systems, tissue engineering scaffolds, and other uses. Minimum requirements of Biomaterials: 1.

NonNon-to toxi xicc (bio (biosa safe fe))

They should be non-pyrogenic, Non-hemolytic, Chronically non-inflammative,  Non-allergenic, Non-carcinogenic, Non-teratogenic, etc.. 2. Effective

They They should should be effecti effective ve functi functiona onally lly,, should should have have good good perfor performan mance, ce, durability,etc. 3. Ste Steril riliza izable ble

They can be sterilizable by using Ethylene oxide, γ-Irradiation, Electron beams, Autoclave, Dry heating, etc 4. Biocom Biocompat patibl iblee

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 polymerr which which underg undergoes oes a physica physicall change change in the Thermoresponsive polymer is a polyme  presence of external thermal stimuli. The ability to undergo such changes under easily contro controlle lled d condit condition ionss puts puts this this class class of polyme polymers rs into into the catego category ry of smart smart materia materials. ls. 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) poly(N-isopropylacrylamide) (PNIPAAm).

(e.g. Poly Poly amino amino acids) acids) are branch branched ed copoly copolymer merss where where side side chain chain is Graft Graft polymers polymers (e.g. structu structurall rally y differe different nt from from the main main chain. chain. In the above above figure figure,, graft graft polyme polymerr bearin bearing g hydrophob hydrophobic ic and hydrophilic hydrophilic chains chains undergo undergo self-aggrega self-aggregation tion which in aqueous aqueous medium medium at  proper concentration (Critical Aggregation Concentration) forms colloidal micelle systems havi having ng hydr hydrop opho hobi bicc core core and and hydr hydrop ophi hili licc shel shell. l. Then Then these these acti active ve mole molecu cule less 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:  Examples: Biodegradable Polymers •

Polyglycolic acid

Non-Biodegradable Polymers •

(polyglycolide)

Polyethylene terephthalate (PET), Dacron

•

Polylactic acid (polylactide)

•

 Nylon 6,6

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Poly-3-hydroxybutyrate

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Polyurethanes

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Polydioxanone

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Polytetrafluoroethylene (PTFE)

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Linear polyaliphatic esters

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Polyethylene (low density and high density) plus UHMW

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Polysiloxanes (silicones)

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Poly(methylmethacrylate)

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2.1. •

NON-BIODEGRADABLE NON-BIODEGRADABL E POLYMERS

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

•

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

•

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

•

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.

•

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 microorganisms are present present around around the polymers. Such environments 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 environm environments ents not through through ther thermal mal oxidation, oxidation, photolysi photolysis, s, or radiolysis radiolysis but through through enzymatic or non-enzymatic 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.

•

The degradation time must match the time required.

•

It does not invoke a toxic response.

•

It is metabolized in the body after fulfilling its purpose.

•

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

Mechan Mechanica icall perfor performan mance ce of a biodeg biodegrad radabl ablee polyme polymerr depend dependss on variou variouss factors factors which which includ includee monome monomerr selecti selection, on, initiat initiator or selecti selection, on, proces processs condit condition ionss and the presen presence ce 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 affec affectt the the biod biodeg egra rada dati tion on of the the poly polyme mer. r. Biod Biodeg egra rada dati tion on can can be accom accompl plish ished ed by synthe synthesizi sizing ng polyme polymers rs with with hydro hydrolyt lytical ically ly unstab unstable le linkag linkages es in the backbo backbone. ne. This 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: •

Wate Wa terr pene penetr trate atess the the bulk bulk of the the devi device, ce, atta attack ckin ing g the the chem chemic ical al bond bondss in the the amorph amorphous ous phase phase and conver convertin ting g long long polyme polymerr chains chains into into shorter shorter water-s water-solu oluble ble 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.

•

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 Working Principle Principle:: Poly olymer mer is tak taken and and shap shaped ed as need needed ed,, then then seed seeded ed with ith

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 Diagram of a Ventricular Assist Assist Device

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PTFE

4.

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. 4.1.

MEDI MEDICA CAL L APPL APPLIC ICAT ATIO IONS NS OF BIOA BIOABS BSOR ORBA BALE LE POLY POLYME MERS RS

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 Contact inhibition

Scaffol d

Cellular proliferation Tissue guide

Capsulation

4.2.

Examples

Controlled drug Delivery

APPLICATIONS IN HUMAN BODY

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Organ protection 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 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.

•

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 year s of development is any indication 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 the deve develo lopm pmen entt of bioc biocom ompa pati tible ble mate materia rials ls by biom biomate ateria rials ls scien scienti tists sts and and engineers.

•

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

•

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 surfa surface ce modi modifi ficat catio ion n tech techni niqu ques es for for the the inco incorp rpor orati ation on of low low surfa surface ce ener energy gy fluorocarbon containing surface modifying and bioactive agents.

•

There There is a need need for tailoring tailoring the compos compositio ition n of polyur polyureth ethane aness for the study study of  mech mechan anism ismss of biod biodeg egrad radati ation on and and mode modeli ling ng the the biod biodeg egra rada dati tion on proc process esses es 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.

•

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

•

Still there is need for the development of antimicrobial materials for implantable medi medical cal devi device cess and and also also for for the the deve develo lopm pmen entt of biod biodeg egra rada dabl blee vascu vascula larr graft 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 effectively like certain certain forms of liver failure, paralysis, paralysis, and certain disorders. disorders. “Clearly we are faced with big challenges 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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2.

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3.

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4.

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5.

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6.

“Polyu “Polyureth rethane ane – Featur Features es and Benefits” Benefits”,, www.elast www.elastche chem-ca m-ca.co .com/p m/poly oly.ht .html ml

7.

Y. Ikad Ikada, a, “Int “Inter erfa faci cial al Bio Biocom compati patibi bili lity ty”, ”, in: in: “ Polymers of Biological and   Biomedical Significance”, Significance”, ACS  ACS Symp. Ser., Ser. , S. W. Shalaby, Y. Ikada, R. Lander, J. Williams,Eds.

8.

Gild Gildin ing g DK, DK, and and Reed Reed AM, AM, "Bio "Biode degr grad adab able le Poly Polyme mers rs for for Use Use in Surg Surger ery—  y—  Polyglycolic/Poly(lactic acid) Homo- and Copolymers," Polymer.

9.

Middle Middleton ton,, John C. and Tipto Tipton, n, Arthur Arthur J. (March (March 1998) 1998) Syntheti Syntheticc Biodegra Biodegradab dable le Polymers as Medical Devices (http:/ / www. mddionline.com/ article/ synthetic biodegradable-polymers-medical-devices), Medical Plastics and Biomaterials Magazine.

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Andread Andreadis, is, S., “Polyme “Polymerr in Medicin Medicines”, es”, Tissue Tissue enginee engineerin ring g handout, handout, Februa February ry 2001, University at Buffalo.

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