Natural Biomaterials by Isabel Hand

Background

George Washington's Dentures [13]

Natural biomaterials are any material taken from plants or animals and used to augment, replace, or repair body tissues and organs. The use of natural biomaterials is not a new concept; naturally derived materials has been used by humans for thousands of years. Some of the earliest records of this are from ancient Egypt, whose people used sutures made from animal sinew, coconut shells for injured skulls, and wooden teeth. In Germany in 1891, the first hip replacement surgery was recorded using ivory as the natural material. Recently, biomaterials have had a resurgence onto the scitentific field as a good alternative to synthetic materials [1].

Scientists need viable biomaterials to fulfill certain requirements. The most important criteria are that a biomaterials must be biodegradable, biocompatible, and able to attach and grow cells. In addition, it is important that the material be non-toxic, mechanically similar to the replaced tissue, and relatively cheap and easy to produce. Natural polymers are often already designed to meet these requirements, and therefore are good candidates for use in humans as a biomaterial [1].

However, there are limitations and disadvantages to natural biomaterials that has led to the simultaneously use of many synthetic polymers. Due to natural variations between the material sources, the biomaterials themselves have a certain level of variability that can lead to difficulty in creating a high degree of reproducibility. In addition, these materials can sometimes lead to immune responses unless the material is extremely well purified [2].

Alginate

Laminaria digitata seaweed used to extract alginate [13]

Alginate is extracted from brown seaweed, specifically Laminaria hyperborea, Laminaria digitata, Laminaria japonica, Ascophyllum nodosum, and Macrocystis pyrifera. Recently, scientists have studied creating alginate using bacterial biosynthesis from Azotobacter and Pseudomonas which they believe will allow control over its chemical and physical properties which could lead to more applications. Alginate is comprised of a set of linear copolymers with blocks made of (1,4)-linked β-D-mannuronate (M) and α-L-guluronate (G) residues. These blocks can be composed of either consecutive G or M residues, or alternating G and M residues. The ratio of G and M and the length of each block is determined by the specific source from which it is derived. Only the G blocks cross-link, therefore the ratio of G/M and length of the G block are extremely important in the mechanical strength of the hydrogels. Hydrogels are 3D, crosslinked polymer networks that have a high water content. Alginate is usually crosslinked ionically with cations, most often calcium ions.

Bonded G and M residues of alginate [13]

Matrigel

Matrigel is the name of the commercial product from Corning Life Sciences extracted from Engelbreth-Holm-Swarm mouse sarcoma. The tumor has high amounts of ECM proteins, and the extract yields a product that is approximately 60% laminin, 30% collagen IV, and 8% entactin. The fibrous structures of the laminin and collagen are bridged by entactin to further organize the structure. In addition, the Matrigel porduct contains numerous growth factors that are from the tumor. (datasheet) Matrigel is widely used as a growth-matrix for stem cells because of its high numebr and variety of growth cells which allow it to cultivate cells that are very sensitive to culture environment. One of Matrigel-s most important attributes is its ability to keep stem cells undifferentiated. However, although Matrigel is extremely useful for cell culture, it has high variability. (paper)

Fibrin

Fibrin as a biomaterial is derived from the body’s natural response to injury. Fibrinogen, its precursor, is created in the liver and circulates within mammalian blood. When an injury is sustained, thrombin will cut fibrinogen to form fibrinopeptides A and B.This cut exposes the “knobs” of A and B which interact with “holes. This causes the blood to clot, stopping bleeding. Fibrin is stabilized by Factor XIII, which causes cross linking between fibrins. Fibrin was first purified on a large-scale in the 1940s, and has since become one the the classic biomaterials. Fibrin use as a biomaterial is extremely versatile. Its main benefits are that is is very biocompatible, is able to direct tissue regeneration, and polymerizes very quickly. One of Fibrins first uses was as a skin sealant, which dates back to 1909 when Bergel reported using Fibrin powder to stop bleeding. In 1944, it was reported that fibrin was being used to heal burns on soldiers. The first tissue sealant to receive FDA approval, Tissee, was in 1998, and since then several more sealant brands have gone on the market. Fibrin’s characteristics are valuable for tissue engineering because of its ability to act as a scaffold for tissue repair, and to provide signals for cell growth onto the scaffold.

Collagen

Even before its use in modern science, Collagen has been used by humans as a component of leather, glue, gelatin, and musical strings. In 1881, Joseph Lister and William Macewen independently reported findings on using catgut, a biodegradable suture made from collagen from the small intestine of a sheep. Collagen is the most abundant protein in mammals and has many properties that make it a good choice for both wound healing and tissue engineering. It is composed of three peptides the wind to form a triple helix. These helices can sometimes combine and form large fibers. These collagen networks make up the structure of the ECM. Collagen is widely used in tissue engineering as it is extremely biocompatible, biodegradable , non-toxic, cell interactive, and has high tensile strength and stability. However, collagen does have some major disadvantages. Collagen must be stabilized, often by adding another material, because its easy interaction with cells can cause the cells to reorganize the collagen and disrupt the scaffold. Collagen based materials are available from nearly every biomedical company in many forms, including sponges, fibers, powder, and dressings. Collagen can be extracted from animal tissue, but most commonly is taken from bovine skin and tendons, porcine skin or intestine, and rat tail. For wound dressing, collagen is often used as a sponge or a membrane. It is also used in bone repair, drug delivery, skin replacement, and as an injectable hydrogel.

Myocardial Tissue Engineering

Biomaterials have become an important area of research for cardiac tissue engineering. Scientists are looking into using these materials to create cardiac patches in vitro for the damaged area, to deliver or recruit from nearby cells it increase heart function, and to prevent cardiac remodeling. Both alginate and collagen are widely used because they have high availability and are very biocompatible. Creation of a patch relies on the scaffold material. In 2009, a porous alginate scaffold was used as a culture for fetal rat cardiomyocytes, vascularized in the rat's peritoneal cavity, and then transplanted into the heart as a patch. The formation of functional tissue was improved by adding adhesion and heparin-binding peptides to the alginate scaffold. Additionally, collagen scaffold were used to differentiate cardiomyocytes. An engineered heart tissue (EHT) that has become a standard in research was created in 2002 by mixing cells with Collagen and Matrigel, seeding them into molds, and then using mechanical stretching to form desired tissue. Four weeks after the EHT was transplanted onto the infarcted myocardium of rats thick muscle layers had developed. The second category of myocardial engineering is using an injectable hydrogel to prevent remodeling, repair the heart using endogenous or exogenous cells, and act as a temporary matrix from cell transplantation.In 2012, a thermo-gelling mix of chitosan and collagen was created that forms a gel within 30 minutes in ras with properties that achieve cardiomyocyte survival. Fibrin has been studied as a choice for cell transplantation. Injection of fibrin has shown improved heart function, increased vascularization, decreased scar area and improved ventricle geometry, in animals. In addition, fibrin has shown good results as an agent for cell-delivery. However, studies have shown that fibrin biomaterials may only have short-term effects.

References

[1]The Trouble with Teeth. George Washington's Mount Vernon. 2017. http://www.mountvernon.org/george-washington/the-man-the-myth/the-trouble-with-teeth/

[2]Ige, O; Umoru, L; Aribo, S. (2012) Natural Produts: A minefield of Biomaterials. ISRN Materials Science 2012. https://www.hindawi.com/journals/isrn/2012/983062/#B14

[3]Cuy, J. Natural Polymers. (2004) University of Washington Engineered Biomaterials. https://www.uweb.engr.washington.edu/research/tutorials/naturalpolymers.html