S ILK S ERICIN : A V ERSATILE M ATERIAL FOR T ISSUE E NGINEERING AND D RUG D ELIVERY Huma Mehreen Sadaf 10-arid-1824 Department of Botany

B ACKGROUND.. Tissue engineering is to improve the understanding of tissue pathology to improve or sustain tissue function. Choice of suitable biomaterials is crucial because they must replicate the biological and mechanical functions of the natural extracellular matrix (ECM), thereby representing an artificial ECM. In this regard, growing efforts have been devoted to the study of naturally derived materials because they are biocompatible and have the potential advantage of biological recognition.

B ACKGROUND.. Recently, interest in biomaterials research has shifted increasingly toward functional biomaterials, targeting applications in regenerative medicine through the development of improved tissue scaffolds, and toward new drug delivery systems.

I NTRODUCTION … Silk sericin (SS) is one of the two major proteins forming the silkworm cocoon, the other one is silk fibroin. In the cocoon, fibroin is a fibrous protein in the form of a delicate twin thread and enveloped by successive sticky layers of SS forming the silk.

CONTD… In the silk industry, SS is removed from fibroin to improve the luster, softness, smoothness, whiteness, and dyeability of the fibers while SS is discarded in wastewater.

CONTD… Indeed, SS is an unutilized by-product of the textile industry. SS has recently been proven to exhibit important biological activities, making it potentially useful in pharmacological, cosmetic, and biotechnological applications. Accordingly, much effort has been dedicated to the recovery of SS from industrial wastewater.

E XTRACTION … Sericin, also known as “silk glue”, is a globular protein. In the textile industry, SS is separated from fibroin via the “degumming” of the cocoons and is discharged in wastewater. Several methods based on heat treatment are currently available for the extraction of SS from silk cocoons.

B IOCOMPATIBILITY AND IMMUNOLOGICAL RESPONSE A significant consideration in the application of any biomaterial is its potential activation of the immune system i.e. its biocompatibility. This is in fact one of the main determinants of the success or failure of a biomaterial in tissue engineering and regenerative medicine applications.

C ONTD … The innate immune system is the first barrier to any foreign body in the host and as such, it plays an important role in determining the course of a potential immune response to foreign substances. Therefore, macrophage response through the expression and release of first-response pro-inflammatory cytokines is most often assessed in the biocompatibility evaluation of materials.

CONTD… Sericin was reported to be immunologically inert on the basis that in its soluble form, it failed to induce, the short- and long-term expression and release TNF-α. When associated with crystalline fibroin, triggered significant release of TNF-α from macrophages in comparison with SS alone under the same conditions.

CONTD… This indicates that SS-mediated activation is dependent on physical association with the core fibroin fibers. Moreover, SS did not trigger the production of anti-SS antibodies after intravenous injection in rabbits.

A BILITY TO PROMOTE CELL PROLIFERATION … Serum-free media was supplemented with SS to culture different cells including: Human epithelial cells Human embryonic kidney transformed cells Human hepatoblastoma cells Murine hybridoma It significantly promoted the growth of these cell lines by shortening the lag phase of the cell cycle and by inducing early entrance of the cultures in their logarithmic phase.

SS- BASED BIOMATERIALS FOR TISSUE ENGINEERIN G The polar side chains of SS enable the easy cross- linking and blending of SS with other polymers to yield improved biodegradable materials. Several of techniques are often combined to fabricate SS matrices comprising films, scaffolds, and hydrogels. Stable biomaterials are thus fabricated while achieving the controlled release of soluble SS, which promotes cell growth and tissue regeneration.

BONE TISSUE ENGINEERING SS also attracted much attention in bone tissue engineering. SS was indeed found to effectively promote the growth and proliferation of osteoblasts, which adhered and spread well on SS-coated surfaces.

E FFECT OF SS ON SKIN TISSUES Macroscopically, ROS generation due to chronic exposure of the skin to UV radiation ultimately results in premature skin aging expressed as wrinkle formation, along with hyper-pigmentation and the formation of sunburn cells. SS has skin moisturizing and anti-wrinkle effects, which are due to its high serine content, and its AA composition is very similar to that of the skin’s natural moisturizing factor (NMF). This has led to the use of SS not only in the biomedical field but also in the food and cosmetics industries.

S KIN TISSUE REPAIR WITH SS- BASED MATERIALS … Notably, some skin repair and wound healing materials incorporating SS have already been developed and several clinical trials have been reported whereby SS enhanced the adhesion, migration, and growth of keratinocytes and fibroblasts, increased collagen production, and improved re- epithelialization in skin wounds. Actually, due to the numerous materials proposed in this regard, more clinical trials are to be expected.

W OUND HEALING AND TISSUE REGENERATION … For the growth of keratinocytes and fibroblasts in particular, this has led to new applications of SS in regenerative medicine and as wound-healing biomaterials. These cells, aside from producing regulatory cytokines for the wound healing process, are involved in the re- epithelialization and the production of ECM proteins that play critical roles in healing.

SS: A VEHICLE FOR DRUG DELIVERY … Delivery systems are used to improve the effects of active compounds by targeting their delivery site to achieve the desired bioactivity. Owing to its amphiphilic character (polar side chains and hydrophobic domains), SS may be used as a vehicle as it easily binds charged molecules. Because of their amphiphilic character, the particles efficiently trapped both hydrophobic and hydrophilic drugs.

CONTD… Several SS formulations (films, gels, and sponges) for drug delivery application were reported. The drug release rate was controlled by the type of formulation and SS concentration. Additionally, their small size increase the availability of loaded drugs to less accessible areas such as deeper tissues.

C ONCLUSIONS … SS has been a material of great interest in recent years because of its prospective biomedical and biotechnological applications. Its potential lies in its biochemical and biophysical properties, which vary with the source and method of protein isolation. SS is hence a unique protein due to its properties, and accordingly it has been widely applied in tissue engineering.

F UTURE P ROSPECTS … SS could serve as a vehicle for cell transplantation and as a proliferative inducer. New advancements are likewise needed for the applications of SS in drug delivery systems to take advantage of its interesting properties. However, due to the large amounts of SS eliminated in the silk wastewaters, the cost of its recovery from the silk industry remains high, requiring the development of more efficient and cheaper methods to alleviate this concern.

R EFERENCE … Lallepak L., G. Mario, Y. Guang, W. Qun. Silk sericin: A versatile material for tissue engineering and drug delivery, Biotechnology Advances: 1-40, 2015.