Biological materials are natural biocompatible materials that comprise a whole or a part of a living structure or biomedical device that performs, augments, or replaces a natural function. Biological materials are most often engineered for medical, biotechnology and pharmaceutical applications.

Biological materials are present inside living organisms. They do not contain any metal, ceramic, or synthetic polymer material and have the ability to repair themselves, while synthetic materials do not. In contrast to biological materials, a biomaterial is any combination of synthetic and natural substances (other than drugs) that can be used in the treatment or replacement of any tissue organ or function of the body.

The most important specification for a biological material is that it is biocompatible. Biocompatibility generally means that the material does not cause a response in the host. A more complex definition expands upon this to study the functional and nonfunctional effects of the material on the host as well as the response of the material while in the biological environment. There are many factors associated with biocompatibility and determining the potentially adverse or toxic effects of a material. Procedures are in place which will evaluate the cytotoxicity; acute, subchronic, and chronic toxicity; irritation to skin, eyes, and mucosal surfaces; sensitization; hemocompatibility; short-term implantation effects; genotoxicity; carcinogenicity; and effects on reproduction, including developmental effects. In some cases specific target-organ toxicity needs to be evaluated and biological materials which will support a load within the body need to undergo mechanical property testing.

The critical definition of a biocompatible material includes the ability to integrate into a host without causing an immune reaction. In order to be biocompatible, biological materials must have low or no toxicity or cytotoxicity. Cytotoxicity indicates cell killing ability or characteristics. Cytotoxins are poisonous to cells and therefore biological materials or biocompatible materials should not consist of, release or convert to toxic agents within the body.  Biomechanical considerations are also important in determining the biocompatibility of materials. The mechanical properties of biological materials are related to highly organized and integrated hierarchical assemblies of load-bearing units to support organisms of all sizes. The material must be able to withstand the forces of the body as well as not introduce new forces to the surrounding tissue. 

Testing

Biological materials must pass though several rigorous testing procedures. Tests are broken down by classification and then by type.

Nonfunctional tests- Nonfunctional tests include implanting a sample of the biological material into the soft tissue of a host. This short duration test (days or months) observes the response of the surrounding tissue and the integrity of the material as it is exposed to the host.

Ex-Vivo- Ex-Vivo tests use blood to determine compatibility. The host's blood is shunted through arterial-venous and venous-venous shunts and circulated through the material. This allows researchers to observe the material's response to fluid flow as well as its interaction with the biological materials of the host.

Functional- Functional tests are expensive long term tests which include full proto-types of the medical device and/or biological material. The biological material is implanted into the specific part of the host required for the application. The material must withstand all forces and loads and not cause any adverse reactions within the host.

The types of tests listed below can be classified into one or more the classifications listed above.

In Vitro testing literally means "in glass". In Vitro testing is done in laboratory equipment using cells and tissue. They are used to observe the direct toxic/cytotoxic effects on a target organ. One advantage of this type of testing is that it uses controlled conditions of exposure. This is the first level of testing that all biological materials and medical devices need to go through.

In Vitro testing. License: CC0 Public Domain

In Vivo testing is done "in body" or within a living organism. This type of testing is done when In Vitro tests have shown promising results. There are two types of In Vivo  tests.

Animal models- The biological material or medical device must be tested in animals before any further testing can be done in humans. Animal testing provides some challenges for researchers. It is expensive and the animal must also be a close match to humans. There are also ethical issues with using certain species of animals and the potential for harm to the animal models. Animal testing is highly regulated to ensure that the animals are treated safely and the researchers are getting quality data. A negative result in animal testing prevents further testing in humans but even a positive result doesn't mean that the material will be safe in humans.

Clinical trials- Human trials are the last step in the testing process for biological materials. Clinical trials are generally long term studies which expose human patients to the biological material and/or medical device. These tests are expensive and highly regulated by health organizations. 

The evaluation of biocompatibility for the biological material should include a description, its intended use, degree of body contact, chemical nature of the materials, a review of available toxicity and bioavailability data for each chemical component, and a justification for the tests conducted to evaluate all potential toxic end points. 

Types of Biological Materials

Many materials are considered biocompatible or biological materials natural materials such as human derived, natural materials, laboratory support products, and application specific products.

Human Derived

Antibodies- Antibodies are specialized proteins. They are produced when an antigen is introduced into the body and they have the ability to combine with that antigen to destroy it.

Blood and plasma- Blood contains white and red blood cells which transport nutrients and removes wastes throughout the body. Plasma is the liquid part of the blood which contains antibodies and other proteins but does not contain cells. Blood and plasma can be donated and used in medical procedures.

Blood cells; Image Credit: getimagefree.com

DNA-Deoxyribonucleic acid (DNA) is the nucleic acid that carries genetic information. It is found primarily in the nucleus of all living cells.

Enzymes- Enzymes are proteins that cause or accelerate changes in other substances.

Peptides- Peptides are molecules small enough to be synthesized from the constituent amino acid.

Proteins- Proteins are large molecules composed or one or more chains or amino acids. They are required for the structure, function, and regulation of the body's cells, tissues and living organs.

RNA-Ribonucleic acid (RNA) is similar to DNA but contains ribose instead of deoxyribose. RNA plays a critical role in protein synthesis.

DNA; License: CC0 Public Domain

Natural Materials

Hydroxyapatite- Hydroxyapatite is a natural mineral found in bone. It is also a naturally occurring ceramic material.

Artificial tissue- Artificial tissue is the construction of tissue material outside of the body using several types of skin cells.

Bone and tissue- Bone and tissue can also be collected from other living or once-living organisms such as cadavers, animals, and human donors.

Bio-polymers- Bio-polymers are derived from renewable resources such as cellulosic plastics like cellulose acetate, starch plastics, and corn-derived plastics. They evolve to function as cellular components of the organism.

• Starch- Starch is a carbohydrate found in plant tissues. It is an important nutrient and can be prepared as a white amorphous powder. Starch is a biodegradable material and can easily and inexpensively be converted into a bio-polymer.

• Sugars- Sugar (sucrose saccharose) is a white crystalline carbohydrate found in many plants. Sugar is a potential scaffold material for stem cell transplantation.

• Cellulose-Cellulose is a long chain of linked sugar molecules. It is a natural polymer that gives wood its strength. It is a basic building block for many paper and textile products as well as a large selection of biopolymers.

Laboratory Support Products

Cell culture growth media- Growth media is a gel or liquid that contains nutrients and components to support cell or microorganism growth. Different types of media are available for different types of cells.

Cell culture in a petri dish. Image Credit: kaibara87 / CC BY 2.0

Cell scaffolding- Cell scaffolding is an artificial structure used to support three-dimensional tissue formation. They allow for cell attachment and for certain biological and mechanical forces to influence cell development. Cell scaffolding can be made from a variety of materials including collagen and polyesters. Scaffolding is a critical component in the field of tissue engineering.

Cell lines and cultures- Cells can survive outside of an organism if grown and maintained in a special media. Cell lines are the cells grown from a sample. The process of growing microorganisms is called culturing.

Application Specific Products

Model animals -- Model animals are animals used for the testing of biological materials.

Wound closing and suture materials -- Natural suture material consists of surgical gut, which is a twisted fiber formed from the collagen of the intestines of sheep or cows. It is an absorbable material and is used to seal the dermis and subcutaneous tissue. Non-absorbable natural materials such as surgical steel, silk, cotton, and linen, are noted for their resistance to degradation by living tissues.

Features

Special features available with biological materials may include:

• Corrosion resistant materials have inert and corrosion resistant properties against the effects of body fluids.
• Modulus tailored materials can match bone modulus to improve strength and function.
• Low toxicity to cells reduces the chances that cells will mutate or die when exposed to the material.
• Osteostimulative materials stimulate osteoblast proliferation and differentiation for stronger bone substitute materials.
• Growth enhancing materials are added to cell media to promote cell line growth. 

Applications

Biological materials are an important part of biological and biomedical research. The use of biological materials is generally safer for human patients by reducing the chance of infection and rejection. Biological materials can be found in many industries including education, research, medicine, dentistry, engineering, and paper and textile development. Examples of biological material application are given below.

Regulations

The study and use of biological materials is under strict regulation and requires specific protocols to ensure the safety of the researchers, doctors, and patients who use the material. A brief list of these acts is listed below:

• Food and Drug Administration
  • Medical Device Amendment of the U.S. FDA Act 1976
  • Safe Medical Devices Act of 1990
• American Society for Testing Materials (ASTM)
• National Institutes of Health (NIH) 

Resources

Considerations for the Biocompatibility Evaluation of Medical Devices

What is Cellulose?

Flashcards: Medical Laboratory Glossary

Combining stem cells and biomaterial scaffolds for constructing tissues and cell delivery

Dee, Kay C., David A. Puleo, and Rena Bizios. An Introduction to Tissue-biomaterial Interactions. Hoboken, NJ:

Wiley-Liss, 2002. Print.

Materials for Wound Closure

Mohanty, Amar K., Manjusri Misra, and Lawrence T. Drzal. Natural Fibers, Biopolymers, and Biocomposites. Boca Raton, FL: Taylor & Francis, 2005. Print.

O'Hare, Sheila, and C. K. Atterwill. In Vitro Toxicity Testing Protocols. Totowa, NJ: Humana, 1995. Print.

Image Credit:

U.S. Government Works | Public Domain | getimagefree.com | Public Domain | Flickr: kaibara87