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silk

Applications as a Biomaterial

As stated above, silk has been considered as a luxurious textile since 3630BC. However, it started to serve also as a biomedical material for suture in surgeries decades ago. In the past 30 years, it has been widely studied and used as a biomaterial, which refers to materials used for medical applications in organisms, due to its excellent properties, including remarkable mechanical properties, comparative biocompatibility, tunable degradation rates in vitro and in vivo, the ease to load cellular growth factors (for example, BMP-2), and the ability to be processed into several other formats such as films, gels, particles, and scaffolds. Silks from Bombyx mori, a kind of cultivated silkworm, are the most widely investigated silks.

Silks derived from Bombyx mori are generally made of two parts: the silk fibroin fiber which contains a light chain of 25kDa and a heavy chain of 350kDa (or 390kDa) linked by a single disulfide bond and a glue-like protein, sericin, comprising 25 to 30 percentage by weight. Silk fibroin contains hydrophobic Beta sheet blocks, interrupted by small hydrophilic groups. And the beta-sheets contribute much to the high mechanical strength of silk fibers, which achieves 740MPa, tens of times that of poly(lactic acid) and hundreds of times that of collagen. This impressive mechanical strength has made silk fibroin very competitive for applications in biomaterials. Indeed, silk fibers have found their way into tendon tissue engineering, where mechanical properties matter greatly. In addition, mechanical properties of silks from various kinds of silkworms vary widely, which provides more choices for their use in tissue engineering.

Most products fabricated from regenerated silk are weak and brittle, with only ~1-2% of the mechanical strength of native silk fibers due to the absence of appropriate secondary and hierarchical structure,

Source Organisms	Tensile strength (g/den)	Tensile modulus (g/den)	Breaking strain (%)
Bombyx mori	4.3–5.2	84–121	10.0–23.4
Antheraea mylitta	2.5–4.5	66–70	26–39
Philosamia cynthia ricini	1.9–3.5	29–31	28.0–24.0
Coscinocera hercules	5±1.2	87±17	12.1±5.1
Hyalophora euryalus	2.7±0.9	59±18	11.1±5.8
Rothschildia hesperis	3.3±0.8	71±16	9.5±4.4
Eupackardia calleta	2.8±0.7	58±18	11.8±5.5
Rothschildia lebeau	3.1±0.8	54±14	15.5±6.7
Antheraea oculea	3.1±0.8	57±15	14.5±6.6
Hyalophora gloveri	2.8±0.4	48±13	19.3±6.9
Copaxa multifenestrata	0.9±0.2	39±6	4.1±2.7

Biocompatibility

Biocompatibility, i.e., the ability to what level the silk will cause an immune response, is definitely a critical issue for biomaterials. The biocompatibility of silk arose during its increasing clinical use. Indeed, wax or silicone is usually used as a coating to avoid fraying and potential immune responses when silk fibers serve as suture materials. Although the lack of detailed characterization of silk fibers, such as the extent of the removal of sericin, the surface chemical properties of coating material, and the process used, make it difficult to determine the real immune response of silk fibers in literature, it is generally believed that sericin is the major cause of immune response. Thus, the removal of sericin is an essential step to assure biocompatibility in biomaterial applications of silk. However, further research fails to prove clearly the contribution of sericin to inflammatory responses based on isolated sericin and sericin based biomaterials. In addition, silk fibroin exhibits an inflammatory response similar to that of tissue culture plastic in vitro when assessed with human mesenchymal stem cells (hMSCs) or lower than collagen and PLA when implant rat MSCs with silk fibroin films in vivo. Thus, appropriate degumming and sterilization will assure the biocompatibility of silk fibroin, which is further validated by in vivo experiments on rats and pigs. There are still concerns about the long-term safety of silk-based biomaterials in the human body in contrast to these promising results. Even though silk sutures serve well, they exist and interact within a limited period depending on the recovery of wounds (several weeks), much shorter than that in tissue engineering. Another concern arises from biodegradation because the biocompatibility of silk fibroin does not necessarily assure the biocompatibility of the decomposed products. In fact, different levels of immune responses and diseases have been triggered by the degraded products of silk fibroin.

Biodegradability

Biodegradability (also known as biodegradation)--the ability to be disintegrated by biological approaches, including bacteria, fungi, and cells--is another significant property of biomaterials today. Biodegradable materials can minimize the pain of patients from surgeries, especially in tissue engineering, there is no need of surgery in order to remove the scaffold implanted. Wang et al. showed the in vivo degradation of silk via aqueous 3-D scaffolds implanted into Lewis rats. Enzymes are the means used to achieve degradation of silk in vitro. Protease XIV from Streptomyces griseus and α-chymotrypsin from bovine pancreases are the two popular enzymes for silk degradation. In addition, gamma-radiation, as well as cell metabolism, can also regulate the degradation of silk.

Compared with synthetic biomaterials such as polyglycolides and polylactides, silk is obviously advantageous in some aspects in biodegradation. The acidic degraded products of polyglycolides and polylactides will decrease the pH of the ambient environment and thus adversely influence the metabolism of cells, which is not an issue for silk. In addition, silk materials can retain strength over a desired period from weeks to months as needed by mediating the content of beta sheets.