The theory behind using spider silk for wound healing purposes dates back to ancient Roman medicine and has since been heavily evaluated for its usefulness for many other biomedical applications.
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Why silk?
Silk is a fibrous protein that is synthesized in the specialized epithelial cells that can be found surrounding the glands of various types of insects. The most common sources of silk include worms of the order Lepidoptera, which include organisms like mites, butterflies and moths, as well as several members of the Arachnida class of organisms, which consists of over 30,000 different species of spiders.
While silk is a general term that is used to describe any type of protein fiber spun by insects, the physical, chemical and biological properties of a given silk material vary depending upon the species from which the material originated from.
Within nature, the tight packaging of the β-sheets that comprise silk fibroin polymers provide support for web formation, nest building, safety lines, egg protection, cocoon formation and the construction of traps.
The same mechanical properties that assist worms and spiders in nature have inspired researchers to incorporate these proteins into various biomaterials. In addition to unique strength and resiliency characteristics, silk is also environmentally stable, non-immunogenic, bioresorbable, biocompatible, biodegradable, morphologically flexible and can be engineered to immobilize growth factors through the modification of amino acid side changes.
Obtaining spider silk
The specific amino acid sequences and movements of the original spider species determine the composition of any spider silk protein. Recent studies on the unique physical properties of spider silk have led to an increased interest in harboring these proteins for different biomedical applications.
The yield of silk that can be obtained from spiders can range from 12 to 137 meters, which is considerably less than the 600 to 900 meters that can be obtained from a single silkworm.
In an effort to increase production rates, researchers have utilized recombinant DNA technology (RDT) to produce spider silk artificially. Some of the unique features of spider silk include high elasticity, tensile strength and lightweight properties.
Biomedical applications
Wound healing
As the largest organ of our body, skin provides a protective external barrier for our internal organs against environmental hazards and harmful pathogens. When a cutaneous wound arises, a cavity is formed that compromises the normally healthy structure and function of the skin tissue.
When the self-repair properties of the skin are insufficient in their ability to health serious wounds like diabetic ulcers, burn injuries or other deep wounds, surgical interventions or bioactive dressing materials can be used.
Spider silk has shown unique potential in a wide range of wound healing applications. In more recent times, when applied to in vitro skin models, native spider silk fibers have been found to significantly improve the development of epidermal layers over fibers and support keratinization. When applied to the burn wounds in vivo, spider silk has demonstrated superb wound healing properties.
In addition to eliminating the occurrence of any adverse reactions in terms of an inflammatory response, the natural degradation of spider silk wound dressings also eliminates any painful changes or dressing removals that would normally cause distress in patients.
The wound healing potential of spider silk fibers has subsequently led to its use in biocompatible sutures for the closure and/or ligation of various soft tissues during ocular, neural and cardiovascular surgeries.
Despite the high tensile strength of spider silk, this material is limited in its antimicrobial properties. As a result, spider silk sutures must often be treated with antimicrobial agents that do not compromise the tenacity, knot strength, surface friction or biocompatible properties of the silk fiber.
In addition to conventional antibiotics that have been used as antimicrobial coatings for spider silk, alternative substances like human-derived antibacterial peptides have also been explored.
Tissue engineering
The biomaterial used for tissue engineering must be carefully selected and thus capable of incorporating the physical, chemical and biological cues that are required to guide cell migration, adhesion and differentiation for the establishment of functional tissues. In addition, the degradation rate of biomaterials used for this purpose must be commensurate with new tissue formation and all for the deposition of new extracellular matrix (ECM).
Many of these mechanisms that are crucial for the assembly and maintenance of tissues is cell adhesion. Since silk-like polymers (SLPs) can be manipulated at the genetic level, bioactive domains like fibronectin can be introduced in an effort to improve the biological performance of these biomaterials.
Fibronectin is a multifunctional and multidomain glycoprotein that plays an important role in various cellular processes by binding to different integrin receptors within the ECM. Of the three different types of fibronectin proteins, fibronectin type II (FNII) is typically found in matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins, which are associated with improved cell adhesion and collagen-binding activities.
In a 2017 study, researchers genetically fused the DNA sequence of spider dragline silk protein (6mer) with the FNII coding sequence to create a novel non-cytotoxic silk-based biopolymer blend.
In addition to efficiently producing the biomaterial at yields that were 10-times higher than other functionalized 6mer-based spider silk proteins, the researchers also found that the chimeric 6mer + FNII material had exceptional mechanical properties that were comparable to other biopolymers such as polylactic acid (PLA), blend films of fibroin with human-like recombinant collagen and recombinant spider silk films.
This biomaterial did not cause any cytotoxicity to normal human skin fibroblasts when evaluated in vitro and was also found to promote cell adhesion in this model.
References and Further Reading
Vepari, C., & Kaplan, D. L. (2007). Silk as a biomaterial. Progress in Polymer Science 32(8-9); 991-1007. doi:10.1016/j.progpolymsci.2007.05.013.
Chouhan, D., & Mandal, B. B. (2020). Silk biomaterials in wound healing and skin regeneration therapeutics: From bench to bedside. Act Biomaterialia 103; 24-51. doi:10.1016/j.actbio.2019.11.050.
Pereira, A. M., Machado, R., da Costa, A., et al. (2017). Silk-based biomaterials functionalized with fibronectin type II promotes cell adhesion. Acta Biomaterialia 47(1); 50-59. doi:10.1016/j.actbio.2016.10.002.
Liebsch, C., Bucan, V., Menger, B., et al. (2018). Preliminary investigations of spider silk in wounds in vivo – Implications for an innovative wound dressing. Burns 44(7). doi:10.1016/j.burns.2018.03.016.
Franco, A. R., Fernandes, E. M., Rodrigues, M. T., et al. (2019). Antimicrobial coating of spider silk to prevent bacterial attachment on silk surgical sutures. Act Biomaterialia 99; 236-246. doi:10.1016/j.actbio.2019.09.004.