The Contribution of Silk Proteins to Healthcare and Wellness
Ana L. Oliveira, Viviana P. Ribeiro Universidade Católica Portuguesa, CBQF-Centro de Biotecnologia e Química Fina–Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
Significant advances in the field of biomaterials research have led to remarkable technological breakthroughs in the healthcare industry. At the same time, the search for sustainable biomaterials with multiple applications that can be processed through eco-friendly fabrication strategies is gaining momentum. Silk biopolymers have gathered attention, especially due to their remarkable structural properties, cost-effectiveness, abundant availability, and green processing.
The potential applications of silk fibroin and sericin from different species have been extensively explored in biomedical research and as tissue-engineered grafts. This post will focus on the inherent silk properties endowed by nature that allow great advancements in silk applications, extended not only to tissue engineering but also to pharmacology, biomedical imaging, electronics, optical devices, the food industry, cosmetics and bioremediation products.
Exploring Natural Silk Proteins
In recent years, research on biomaterials has increased significantly, allowing the introduction of innovative materials with transversal applications in different areas. Silk proteins are no exception as their role in nature is widely recognized, and, therefore, the sources of production are highly exploited. In addition, its easy processing, high reproducibility and structural stability make silk a desired protein for applications in the biomedical, biotechnology, electronics or food industry.
Silk has been known for centuries for being well-tolerated in the human body as a surgical suture, not to mention its well-established role in the fashion industry.
As natural polymers, silks play an imperative role in nature with specific functions of protection, survival and reproduction of species (insects and arthropods). The main sources of silk include the spider and the silkworm. Spider silks are known for the superior mechanical properties of produced fibers. However, they are limited by their low collection capacity. Conversely, domesticated silkworms, especially the genetically modified Bombyx mori, are known for producing highly reproducible silk fibers with good mechanical properties and favorable amounts. They are being explored in different countries, including India, China and Thailand.
Is Silk a Sustainable and Renewable Biomaterial?
Although silk is a natural, biocompatible and functionalizable material, its processing methods often involve time-consuming procedures that may lead to detrimental effects on the environment. This drawback contradicts one of the primary motivations for using silk as a potential biomaterial for scientific and industrial research, namely its eco-friendly origin, properties, and processing (Figure 1). Moreover, the effects of the processing technologies on silk proteins’ microstructure and properties are still poorly understood.
Processing silk fibers always involves a degumming process that separates the fibroin core protein from the sericin coat protein. This can be 100% clean by simply using boiling water to dissolve and extract the sericin. However, it does not allow for the full removal of sericin from the silk fiber, leading to lower extraction yields of sericin, while fibroin will still be left with sericin residues.
Silk sericin has long been considered a wastewater-derived material by the silk fibroin extraction textile industry. However, its biocompatible and bioactive properties have been explored in recent years, opening many new possibilities for creating valued-added products from this protein. Silk fibroin, on the other hand, requires the subsequent use of chemical solvents for dissolution in an aqueous solution, which can be hazardous and eco-unfriendly.
Regardless of the different structural properties inherent in silk fibroin and silk sericin, we can assume that sericin extraction can have a lower environmental impact compared to silk fibroin. Nevertheless, environmental awareness and legislation are now evolving, forcing the use of new ecological solvents for silk fibroin processing.
Obtaining silk fibroin and silk sericin in a water-soluble form implies bringing these proteins to random-coil conformation. Enzymatically cross-linked silk fibroin/sericin hydrogels have been proposed through fibroin and sericin aqueous solutions. However, the different microstructural properties of silk proteins can drive conformational changes over time.
Silk fibroin naturally undergoes beta-sheet conformation, regardless of the storage conditions. As for aqueous silk sericin, it exhibits temperature-dependent self-gelation behavior while maintaining a predominant amorphous conformation.
The conformational properties of silk-based materials can be ultimately affected by physical and chemical treatments that induce silk I or silk II crystallization according to the primary application required. The main problem is that not all these methods are entirely green, especially chemical induction.
Switching to eco-friendly technologies to process silk has gained popularity in materials science and research. But more is needed to reduce the negative environmental impacts and find the ideal eco-friendly methods to maximize the potential of these proteins.
Figure 1. Main properties and applications of silk as a sustainable material.
Revolutionizing Silk: Emerging Innovations and Applications
Silk proteins display a wide range of properties that make them exceptional polymers and highly valued biomaterials. Silk fibroin has been recognized as a supporting structure in reconstructive surgery by the FDA, being processed into different forms of scaffolds, sponges, films, or hydrogels for tissue engineering applications.
Several studies reported that silk fibroin biocompatibility is magnified after the removal of sericin, which over time proved to be inconsistent due to the minimal inflammatory response of silk sericin, especially in combination with different forms of silk fibroin. In fact, silk sericin proved to have exceptional structural and conformational properties that, in the correct balance, can induce a desired cellular activity and guide appropriate tissue regeneration.
Drug delivery and Pharmaceutics
Advances in biomedicine and nanofabrication technologies have empowered the functionalization of silk-based materials, expanding their application as drug delivery systems or biosensors. Additionally, there is an increasing focus on using silk in flexible electronics and photonic devices, owing to its biocompatibility and capacity to develop lightweight, resilient, flexible and safe devices.
Silk proteins are well known to be composed at different extents by alternating hydrophilic and hydrophobic blocks that result in highly soluble aqueous solutions under mild conditions. This is crucial for the fabrication of silk-based drug-carrier biomaterials, such as hydrogels, microspheres or nanoparticles, that can be stable for encapsulating drugs and bioactive molecules of interest.
Nevertheless, it is important to highlight that the performance of silk can vary depending on the type of silk protein used (sericin or fibroin) and its source. Batch-to-batch variability can be minimized by genetic control of the producing species.
Electronics and Optical Devices
Apart from the increasingly innovative applications in the biomedical field, silk-based materials have been applied in combination with other nanomaterials for specialized targets, including sensing, resistance to ultraviolet light and cell visualization.
The recent demand for smart and wearable materials has put silk in the spotlight. Recently silk has been explored as an active element in electronics, e.g., biosensing devices, electrode materials, switching memory devices, and the development of optical devices. The unique, robust mechanical properties, conductivity, tunable degradation and fabrication in different forms justify its demand.
The Food and Drug Administration (FDA) has already approved silk-based materials in electronic devices to be implantable in biomedical and healthcare applications. Silk sensors have also been shown to be important for monitoring food quality by integrating silk substrates within wireless antennas. Nevertheless, there are still several technical challenges in developing silk-based electronic or optic devices.
Bioremediation involves using micro-organisms to reduce or eliminate pollution through the biological degradation of pollutants into harmless compounds. Silk has been widely used as ultrafine powders, membranes or particles, either alone or in combination with other polymers, to eliminate heavy metals from aqueous solutions, purify water, an absorbent for harmful dyes and function as air filtration.
Silk-based nanofilters have shown high efficiency in air cleaning, and silk fibers can be used to prepare superhydrophobic sorbents that can remove oil from water surfaces. These approaches promote the value of silk fibers for clean-up applications.
According to the International Cosmetic Ingredient Dictionary and Handbook (Dictionary), there are 10 silk protein ingredients currently used in cosmetics: fibroin, hydrolyzed fibroin, hydrolyzed sericin, hydrolyzed silk, MEA-hydrolyzed silk, sericin, silk, silk extract, silk powder, silkworm cocoon extract. This reveals that silk has been deeply explored in this field with promising outcomes.
In the particular case of silk sericin, cosmetics and dermatology were the first fields that valued its potential due to its singular physical-chemical properties, moisture absorption and retention capacity that can increase the hydration potential of creams, elasticity and anti-wrinkle effects. Several research studies have demonstrated that silk sericin possesses inherent photo-protective properties enhancing the light screening effect of UV filters. Moreover, the antioxidant, antibacterial, and immunomodulatory properties of silk sericin positioned this protein as top high-value-added products from industry applied in cosmetics (i.e., nail, skin and hair cosmetics) and pharmaceutics.
Plastic pollution is one of the main concerns for environmentalists. Significant efforts have been made to avoid the use of non-biodegradable and non-renewable synthetic polymers as plastic food packaging materials, whose waste ends up in landfills and polluting oceans. As a result, the interest in biodegradable biopolymers for food packaging has escalated in the last decade.
Silk fibroin has been highlighted due to its biodegradability and low water vapor permeability, and different types of films and coaters have been prepared through solution casting and electrospinning for food packaging.
In a different approach, water-based silk fibroin suspensions were proposed to coat the surface of food. The self-assembly capacity of the protein helps to enhance the shelf-life period of the food at room temperature conditions by decreasing the moisture loss and cellular respiration rate. Dip coatings were tested on bananas and strawberries as a proof of concept, showing that silk fibroin membranes of micrometer thickness helped to maintain the physiology of the fruits after harvesting. This is highly innovative for preserving food freshness over long distances.
Another interesting use is the application of silk particles to control flavorless and odor-free food and packaging. So far, silk sericin has shown its potential in the food industry for its non-toxicity, moisture-retaining capacity, anti-oxidant properties, emulsification and as an anti-frosting agent. It was observed that silk sericin can improve the digestion properties and absorption of bread when added in specific amounts.
Globally, increasing studies have shown the potential of silk protein for the protection of baby food due to its capacity to prevent skin diseases like atopic skin or asthma or even in the production of functional food to prevent neurodegenerative diseases such as Parkinson’s.
Exploring Opportunities and Overcoming Challenges
As the world population continues to grow, there is an increasing need to develop novel biomedical and healthcare solutions. Silk-based biomaterials are quite promising in this regard. While silk-based products have been demonstrating a remarkable potential for tissue engineering, their translation to clinical practice remains a future goal.
The field of silk-based biomedical imaging, sensing, and electronics is also in its early stages but progressing toward achieving the efficacy of traditional products. Additionally, the cosmetic and food industry stand to benefit from the implementation of silk-based modalities, as well as areas like bioremediation, where silk may provide cost-effective solutions for cleaning water contaminated with heavy metals or other pollutants.
Silk has found its purpose in different fields, continuing to fascinate researchers worldwide. Although there are still many restrictions regarding regulatory aspects for the development of silk-based technologies and products, the benefits of using silk outweigh the challenges, and efforts will continue to be made to produce commercially available silk-based products.
About the Authors
Ana Leite Oliveira is the head of the Biomaterials and Biomedical Technology Laboratory at CBQF and Professor at Escola Superior de Biotecnologia, Universidade Católica Portuguesa, where she is the Director of the Master of Biomedical Engineering. She holds a PhD from the University of Minho (2008), collaborating with Depuy Orthopaedics,Inc. (Johnson&Johnson), USA and CSIC, Madrid, followed by a Post-Doc with Tufts University, Boston, USA. She gained expertise in biomaterials for tissue regeneration, working presently in skin-related applications. She has published over 80 international peer reviewed articles and book chapters and participated in more than 100 international scientific and technological conferences, mostly as an oral presenter or as an invited lecturer. The innovation in her work generated 5 patents and links to industry, working with companies to reach new products/processes. She successfully prepared/coordinated various projects funded by National/European agencies and private companies.
Since 2008 she has been assisting the European Commission as an Independent Expert for the Research Executive Agency (REA) in several actions, such as Marie Skłodowska-Curie actions (H2020, FP7), Cost Actions and FET OPEN Calls. Presently, she is Vice-chair for the FET OPEN programme, while also monitoring ongoing FET OPEN projects, in the role of Innovation Radar and as Technical Monitor.
Viviana Ribeiro concluded in 2018 her PhD in Tissue Engineering, Regenerative Medicine and Stem Cells at the University of Minho, in collaboration with the Conselho Superior de Investigacione Científicas (CSIC, Madrid). That same year, integrated two research projects as a postdoctoral fellow at the University of Minho and later in 2019, she was awarded with two Junior Doctoral Researcher contract at the same institution. Since October 2022, she has been a member of the Centre for Biotechnology and Fine Chemistry (CBQF) of School of Biotechnology (ESB) of the Portuguese Catholic University of Porto, as a Doctorate Junior Researcher, developing research in the scientific area of biotechnology, biomaterials applied in tissue engineering and regenerative medicine. She performs teaching activities to the Master in Biomedical Engineering (ESB, Porto), course units of Tissue Engineering and Biofabrication and Biomaterials II. Her proficiency resulted in 4 patents, more than 60 publications (articles in international journals, book chapters and conferences) and more than 40 presentations at scientific meetings. She has been involved in the preparation and submission of several national and international project.
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