BIOMATERIALS

M. Kumari 

A biomaterial is any substance that has been engineered to interact with biological systems for medical purposes. It is either a therapeutic like in the repair / replace a tissue function of the body or a diagnostic one. It is nuvelle only about fifty year’s old science. The study of biomaterials is known as Biomaterial Science or Biomedical Engineering.  It encompasses elements of medicine, biology, chemistry, tissue engineering and materials science.   It can be derived from nature as well as synthesized using various chemical approaches using polymers, composite materials and metallic components.

The biomaterials are mostly used for different treatments which comprise whole or part of a living structure or bio-medical devices which replace a natural function or performs as well.   Such functions may be benign, like being used for a heart valve, or may be bioactive with a more interactive functionality such as Hydroxy-apatite coated hip implants. Biomaterials are also used every day in dental applications, surgery, and drug delivery. For example, a construct with impregnated pharmaceutical products can be placed into the body, which permits the prolonged release of a drug over an extended period of time. A biomaterial may also be an Autograft , Allograft or Xenograft used as a transplant material.

The key properties of the Biomaterials

The prime characters of biomaterials are that it does not illicit and adverse reaction when placed into service. The main key properties are following:

1.      Metallic biomaterials are used for load bearing applications and must have sufficient fatigue strength to endure the rigors of daily activity.

2.      Ceramic biomaterials are generally used for their hardness and wear resistance for application such as articulating surfaces in joints and in teeth as well as bone bonding surface in implants.

3.      Polymeric materials are usually used for their flexibility and stability, but have also been used for low friction articulating surface.

The most common applications of Biomaterials are following:

APPLICATION OF BIOMATERIALS

       I.            Joint replacements  

    II.            Bone plates  

 III.            Bone cement  

 IV.            Artificial ligaments and tendons  

    V.            Dental implants for tooth fixation  

 VI.            Blood vessel prostheses  

VII.            Heart valves etc.

The Biomaterials useful in above applications are must be compatible with the body with clinical settings. All manufacturing companies are also required to ensure traceability of all of their products so that if a defective product is discovered, others in the same batch may be traced.

HISTORICAL DEVELOPMENT

Some of the earliest biomaterial applications were as far back as ancient Phoenicia where loose teeth were bound together with gold wires for tying artificial ones to neighboring teeth. In the early 1900’s bone plates were successfully implemented to stabilize bone fractures and to accelerate their healing. While by the time of the 1950’s to 60’s, blood vessel replacement were in clinical trials and artificial heart valves and hip joints were in development.

DESIGN FACTORS

Even in the preliminary stages of this field, surgeons and engineers identified materials and design problems that resulted in premature loss of implant function through mechanical failure, corrosion or inadequate biocompatibility of the component. Key factors in a biomaterial usage are its biocompatibility, bio-functionality, and availability to a lesser extent. Ceramics are ideal candidates with respect to all the above functions, except for their brittle behavior.

When a synthetic material is placed within the human body, tissue reacts towards the implant in a variety of ways depending on the material type. The mechanism of tissue interaction (if any) depends on the tissue response to the implant surface. In general, there are three terms in which a biomaterial may be described in or classified into representing the tissues responses. These are bio-inert, bio-resorbable, and bioactive, which are well covered in range of excellent review papers.CLASSIFICATIONS

BIOINERT BIOMATERIALS

The term bio-inert refers to any material that once placed in the human body has minimal interaction with its surrounding tissue, examples of these are stainless steel, titanium, alumina, partially stabilized zirconia, and ultra high molecular weight polyethylene. Generally a fibrous capsule might form around bio-inert implants hence its bio-functionality relies on tissue integration through the implant.

BIOACTIVE BIOMATERIALS

Bioactive refers to a material, which upon being placed within the human body interacts with the surrounding bone and in some cases, even soft tissue. This occurs through a time – dependent kinetic modification of the surface, triggered by their implantation within the living bone. An ion – exchange reaction between the bioactive implant and surrounding body fluids – results in the formation of a biologically active carbonate apatite (CHAp) layer on the implant that is chemically and crystallo-graphically equivalent to the mineral phase in bone. Prime examples of these materials are synthetic hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂], glass ceramic A-W and bio-glass.

BIORESORBABLE BIOMATERIALS

Bio-resorbable refers to a material that upon placement within the human body starts to dissolve and slowly replaced by advancing tissue (such as bone). Common examples of bio-resorbable materials are tricalcium phosphate [Ca₃(PO₄)₂] and Poly (lactic-co-glycolic acid) copolymers. Calcium oxide, calcium carbonate and gypsum are other common materials that have been utilized during the last three decades.

POLY (LACTIC-CO-GLYCOLIC ACID): IMPORTANT BIOMATERIALS

It is a copolymer which is used in a host of Food and Drug Administration (FDA) approved therapeutic devices, owing to its biodegradability and biocompatibility. Poly (lactic-co-glycolic-acid) (PLGA) is synthesized by means of ring-opening co-polymerization of two different monomers, the cyclic dimers (1,4-dioxane-2,5-diones) of glycolic acid and lactic acid. Polymers can be synthesized as either random or block copolymers thereby imparting additional polymer properties. Common catalysts used in the preparation of this polymer include tin(II) 2-ethylhexanoate, tin(II) alkoxides, or aluminum isopropoxide. During polymerization, successive mono-meric units (of glycolic or lactic acid) are linked together in PLGA by ester linkages, thus yielding a linear, aliphaticpolyester as a product.

Depending on the ratio of lactide to glycolide used for the polymerization, different forms of PLGA can be obtained: these are usually identified in regard to the molar ratio of the monomers used (e.g. PLGA 75:25 identifies a copolymer whose composition is 75% lactic acid and 25% glycolic acid). The crystallinity of PLGAs will vary from fully amorphous to fully crystalline depending on block structure and molar ratio. PLGAs typically show a glass transition temperature in the range of 40-60 °C. PLGA can be dissolved by a wide range of solvents, depending on composition. Higher lactide polymers can be dissolved using chlorinated solvents whereas higher glycolide materials will require the use of fluorinated solvents such as HFIP.

PLGA degrades by hydrolysis of its ester linkages in the presence of water. It has been shown that the time required for degradation of PLGA is related to the monomers' ratio used in production: the higher the content of glycolide units, the lower the time required for degradation as compared to predominantly lactide materials. An exception to this rule is the copolymer with 50:50 monomers' ratio which exhibits the faster degradation (about two months). In addition, polymers that are end-capped with esters (as opposed to the freecarboxylic acid) demonstrate longer degradation half-lives.

PLGA has been successful as a biodegradable polymer because it undergoes hydrolysis in the body to produce the original monomers, lactic acid and glycolic acid. These two monomers under normal physiological conditions are by-products of various metabolic pathways in the body. Since the body effectively deals with the two monomers, there is minimal systemic toxicity associated with using PLGA for drug delivery or biomaterial applications. Also, the possibility to tailor the polymer degradation time by altering the ratio of the monomers used during synthesis has made PLGA a common choice in the production of a variety of biomedical devices, such as, grafts, sutures, implants, prosthetic devices, surgical sealant films, micro and nanoparticles.  Specific examples of use include:

a.       Successful in the delivery of amoxicillin for the treatment listeriosis (treatment of Listeria monocytogenes infection).

b.      A commercially available drug delivery device using PLGA is Lupron Depot for the treatment of advanced prostate cancer.

c.       Prophylactic delivery of the antibiotic vancomycin into the central nervous system when applied to the surface of the brain after brain surgery

Bibliography

1. http://pubs.rsc.org/en/content/articlelanding/2001/dt/b007852m#!divAbstract.
2. http://www.azom.com/article.aspx?ArticleID=2630
3. https://en.wikipedia.org/wiki/PLGA
4. Farazuddin, Mohammad; Chauhan, Arun; Khan, Raza M.M.; Owais, Mohammad.  (2010-08-05). "Amoxicillin bearing microparticles: potential in treatment of Listeria monocytogenes infection in Swiss albino mice". Bioscience Reports (* Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India; and, † Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India.: Biochemical Society) 31 (4): 265–72. doi:10.1042/BSR20100027
5. Dissolvable Plastic Nanofibers could Treat Brain Infections".Scientific Computing (Advantage Business Media). August 28, 2013. Retrieved September 3, 2013.
6. Pavot, V; Berthet, M; Rességuier, J; Legaz, S; Handké, N; Gilbert, SC; Paul, S; Verrier, B (December 2014). "Poly(lactic acid) and poly(lactic-co-glycolic acid) particles as versatile carrier platforms for vaccine delivery.". Nanomedicine (London, England) 9 (17): 2703–18. doi:10.2217/nnm.14.156.