We ask every team to think deeply and creatively about whether their project is responsible and good for the world. Consider how the world affects your work and how your work affects the world.
In the past, adhesive research primarily centered on situations where exposure to water was avoided until the adhesive had set. However, recent advancements in automotive manufacturing, robotics, and healthcare necessitate the development of underwater adhesives capable of spreading, bonding, curing, and performing effectively even in wet conditions. Tissue engineering, for instance, envisions adhesives as successors to traditional sutures for sealing wounds and preventing the loss of bodily fluids. This makes it crucial to tackle the challenges posed by water in adhesive applications.
We initially sought to identify a biomaterial that would serve as a basis for our project design and then identified Caddisflies as an understudied but versatile material. Then we focused on the silk genes of the casemaker genera after feedback from Prof. Russell Stewart indicated that casemaker caddisfly silk would likely have greater adhesive properties than that of cocoon caddisfly. Eventually, we chose to focus on the G. pellucidus silk fibroin genes.
Our project Caddisilk seeks to develop an easily manufactured alternative to the current industrial underwater adhesives which release harmful microplastics and polyfluoroalkyl substances (PFAS) into organics. Caddisfly silk is non-cytotoxic, biodegradable, and potentially synthesizable through expression in E. coli. Additionally, it has potential application as a wound sealant in medical settings due to its ability to be thermally sterilized without losing the integrity of its physical and chemical properties.
We reviewed the literature on the design requirements and guidelines for underwater adhesives and found that caddisfly silk satisfied all identified suggestions listed: (1) a flexible polymer structure (2) hydrophilic side chains that displace water from hydrophobic interior structure (3) the ability to be applied and cure in liquid solution (4) solvent-free polymer application (5) tensile and adhesive strength comparable to other silks (6) non-cytotoxicity towards human cells.
We also conducted market research on the potential applications of a water-proof adhesive, finding that there was a wide range of industries (aerospace exploration, marine conservation/exploration, health/medicine) seeking to develop and use a waterproof adhesive. Many environmental agencies also are seeking to reduce the use of volatile organic compounds and other toxic solvents involved in polymer manufacturing and curing. Our frugal bioreactor would limit the need for human labor and insect maintenance compared to that of the silkworm silk industry, reducing any ethical risks.
Russell Stewart introduced our team to Prof. Paul Frandsen and Gabi Jijon. Our team requested DNA sequences to design and order plasmids and also expressed our intention to use caddisfly larvae as a control group to compare our synthetic product to the natural material created by caddisworms. Paul Frandsen provided information about specific caddisfly species and their sequences and suggested that caddisfly silk is best suited to wet environments and should be kept moist for research purposes.
Our team inquired about obtaining caddisfly larvae and mentioned our plan to obtain crystal structures of caddisfly silk. Our team discussed any special storage or handling procedures for the caddisfly cases. Paul Frandsen suggested that caddisfly larvae can be easily obtained by searching in rocky streams, provided some guidance on how to find them, and mentioned the diversity of fibroin sequences and silk material properties across caddisflies.
Our team shared the project's experimental plan and requested advice on conducting rtPCR and selecting the repeat for the truncated version of Hesperophylax magnus fibroin. Our team inquired about Paul's progress in investigating the L-fibroin sequence for Glyphotaelius pellucidus. Our team informed Paul of our decision to proceed with Glyphotaelius pellucidus and requested the L-fibroin sequence for this species. Paul suggested alternative species for comparison, provided a distribution map from GBIF, mentioned his ability to extract the L-fibroin sequence, explained how to obtain caddisfly larvae, and shared insights on the diversity of caddisfly silk.
Gabriela offered to send caddisfly cases and requested information on where to send them. Paul provided the CDS and protein sequence for Hesperophylax magnus and shared published sequences and information. Our team expressed our intent to work with Hesperophylax magnus and requested the DNA sequences. We also mentioned our interest in obtaining caddisfly larvae. Russell offered his and his colleagues' help, introduced Paul and Gabi and inquired about what we wanted to study regarding caddisfly larvae and silk genes. Paul provided our team with L-fibroin sequence-related files, including the annotation of the region, the CDS (introns removed), and the peptide sequence.
These larvae create silk underwater for self-protection. The research revealed that, despite the aquatic environment, the cellular process of silk production in caddisworms closely resembles that of terrestrial arthropods.[1]
In caddisworms, silk production involves two distinct processes within the silk glands: the synthesis of silk fibroin in the posterior region and the production of adhesive glycoproteins in the anterior region. These substances are combined to create functional silk that forms a ribbon coated with adhesive material. At the cellular level, fibroin and glycoproteins are synthesized in separate locations and transported from the rough endoplasmic reticulum (ER) to the Golgi apparatus as transport vesicles. These vesicles gradually merge to form larger secretory granules containing specific proteins. These granules ultimately move to the cell's outer membrane and are released into the lumen through merocrine secretion.[1]
These insects are associated with Lepidoptera, the order that encompasses moths and butterflies known for their silk production. Aquatic caddisflies and their terrestrial counterparts, butterflies and moths, diverged from a common ancestor capable of spinning silk around 250 million years ago.The larvae of many aquatic caddisfly species create adhesive silk from glands on their lower lip (labium), which they use to construct protective shelters or funnel-shaped webs in flowing water for hunting.[1]
The silk produced by Trichoptera insects has been described as flat ribbons, a uniform adhesive sheet, and an extremely fine, irregular mesh embedded in an unstructured layer. More recently, Trichoptera silk has garnered attention as a medical bioadhesive capable of adhering to wet tissues, as it can bond to a wide range of surfaces underwater, both organic and inorganic. Caddisfly silk is primarily composed of large fibroin proteins, a critical factor enabling silk production in aquatic environments.[1]
The caddisworm constructs its silken case by creating a lengthy fiber. This fiber is employed to produce a mesh of loose silken cases. Beneath this network, a compact, buff-colored layer is fashioned. Both the inner and outer surfaces consist of a mesh of silk ribbons. However, the outer surface is denser and less translucent, featuring an additional adhesive coating. This contrast could arise from the presence of cover layers containing an adhesive substance in the intricate composition of the silk ribbon.[1]
The secretions originating from a set of silk glands are emitted through a singular spinneret tube within the mouthpart. Upon encountering a watery environment, these secretions solidify, resulting in the formation of a twin-stranded silk material. Notably, the presence of some visible fibers suggests that these individual silk strands tend to intermingle after their release from the spinneret. Additionally, the paper finds apart from a few 'minor differences, the morphology and structure of the silk glands of caddisworm and silkworm were found to be very similar.'[1]
Caddisfly silk consists of two filaments derived from labial glands and is primarily composed of h-fibroin, which lacks glycoprotein P25 found in silkworm silk. The structural organization of Trichoptera h-fibroin is similar to Lepidoptera, with non-repetitive terminal domains and a central region composed of repeated (SX)nE motifs, separated by glycine-rich regions.[2]
The study aimed to increase the number of high-quality full-length Trichoptera h-fibroin sequences from four to eleven. They identified these sequences from seven genomes, covering different silk usage strategies among caddisflies. The primary structure of these h-fibroins was characterized and compared, and their amino acid composition was compared to terrestrial Lepidoptera for further analysis.[2]
The dataset encompassed various clades of caddisflies with different silk usage strategies, including fixed retreat-making Annulipalpia (3 species), cocoon-making basal Integripalpia (2 species), and tube case-making Integripalpia (6 species). The organization of the h-fibroin gene was found to be similar across the 11 species, characterized by a short exon, a single intron, and a long second exon, resulting in a total length ranging from 18,745 to 30,382 base pairs.[2]
The h-fibroin protein's non-repetitive N- and C-termini were highly conserved not only among different caddisfly clades but also when compared to their sister order, Lepidoptera (specifically, Bombyx mori). The N-terminus contained 105-117 residues, showing substantial conservation with 42.5% identical sites and 74.3% pairwise identity among caddisfly species. When compared to B. mori, the N-terminus had slightly lower pairwise identity (65.4%) and identical sites (11.7%). The C-terminus consisted of 40 residues with 32.5% identical sites, and 65.3% pairwise identity, including a conserved cysteine at position 19 in the C-terminus alignment.[2]
The central region is composed entirely of repetitive sequence blocks and was depicted in various ways in the literature to describe the primary structure of h-fibroin. For instance, Frandsen et al. treated each unique (SX)nE motif as the starting point of a repeat. Structurally, this interpretation implies that each repeat commences with a single (SX)nE ß-strand. In our presentation of the new h-fibroin sequences reported in this study, we have categorized the repeating modules into two parts. First, there is a region featuring a variable number (ranging from 1 to 7) of (SX)nE motifs, each separated by relatively short stretches (8-24 residues) of intervening amino acids. Second, there is a region rich in glycine (G) and/or glycine-proline (GP) with a variable length (ranging from 8 to 144 residues).[2]
Across the sampled taxa, glycine and serine were the most abundant amino acids in h-fibroin, displaying consistency in composition. However, notable differences were observed among caddisfly clades. Retreat-making caddisflies exhibited a high proline content, ranging from 9.9 to 12.3%, while tube case makers had a much lower proportion of proline, ranging from 4 to 5.6%. Cocoon-making caddisflies had even less proline, with a range of 2.1-2.7%[2]
Comparing the amino acid composition of h-fibroins in Trichoptera to terrestrial Lepidoptera, distinct differences emerged. Lepidoptera h-fibroins contained higher levels of alanine compared to Trichoptera. Additionally, the Lepidoptera sequences had a smaller percentage of charged amino acids (aspartic acid and glutamic acid) and positively charged amino acids (arginine and lysine) were also less prevalent in Lepidoptera. Furthermore, the h-fibroins of caddisflies had higher amounts of hydrophobic residues (valine, leucine, and isoleucine) compared to Lepidoptera.[2]
In general, non-essential amino acids such as glycine, alanine, and serine dominate insect silk genes to avoid dietary limitations. However, Trichoptera h-fibroins differ from Lepidoptera h-fibroins, particularly in their low alanine content. This difference likely arises from how the proteins fold. Lepidoptera silk relies on β-sheet structures formed by polyglycine-alanine or polyalanine domains, contributing to silk strength. In contrast, caddisfly h-fibroin β-sheets primarily results from phosphorylated serine blocks interacting with metal ions from their aquatic environment, an adaptation specific to aquatic species.[2]
Both Trichoptera and Lepidoptera h-fibroins have a high serine content, suggesting a common adaptation for aquatic silks. Additionally, caddisflies exhibit a higher percentage of hydrophobic and charged residues, potentially reflecting adaptations for aquatic silks. Previous research on aquatic insects, such as black fly larvae, and water-associated spiders also revealed differences in silk gene sequences compared to terrestrial counterparts.[2]
The paper evaluates the viability of caddisfly silk based on sterilizability. While the paper studies Hydropsyche angustipennis, the overall structure of caddisfly silk is highly conserved across genera as previously mentioned.[3]
Since caddisfly silk does not possess any anti-microbial properties, the material should be able to be sterilized without losing its physical properties and should not inhibit cell growth or cause necrosis and apoptosis. The study prepared liquid extracts by washing fibers from cocoons with phosphate-buffered saline and then supplemented it with amphotericin, penicillin, and streptomycin. This was then sterilized with UV radiation for 15 minutes. Additionally, the study carried out tests to evaluate antiseptic properties. The tensile strength of the fibers was also conducted for year-old samples and recently harvested samples.[3]
Additionally, a study was conducted to assess the morphological characteristics and tensile properties of caddisfly fibers following the guidelines, The tensile strength tests were performed on fibers extracted from two different conditions: immediately after sterilization (referred to as variant I) and after being stored for one year (referred to as variant II). The linear density was calculated using the measured fiber diameters and the known density of caddisfly silk (ρ¼1.45 109 mg/m3, as determined in a prior study. The values for the total breaking force (F) and relative elongation (ε) were consistently determined in dry conditions. The specific strength (tenacity), denoted as Wt, was calculated based on the averaged total breaking force (F) and linear density (Tt) of the fibers.[3]
The tensile properties of silk fibers were assessed, and the study revealed a gradual decrease in tensile strength as the breaking force increased, which was attributed to the progressive breaking of individual fibrils and filaments in the fibers. The highest breaking force values were observed after Tyndallization and autoclaving. The relative fiber elongation values varied depending on the sterilization method, with the highest values found in control samples.[3]
In the heat resistance test, a thermogram revealed two distinct mass loss ranges: the first, associated with water evaporation, occurred between room temperature and 150°C, and a plateau was observed between 150°C and 200°C, indicating thermal stability. The second mass loss range, between 200°C and 500°C, was attributed to pyrolysis. The study found that commonly used high-temperature sterilization methods did not degrade the fibers.[3]
Of the different sterilization methods applied, tyndallization and autoclaving are the most effective in eliminating bacterial growth. UV irradiation and ethanol treatment reduced bacterial colonies but didn't eliminate them.[3]
The text discusses the conflicting relationship between water and adhesives, with a focus on the failure of most man-made adhesives in underwater environments. It highlights the ability of certain marine organisms, such as sandcastle worms and mussels, to adhere underwater using natural protein-based adhesives. The text outlines the structure of the review, which covers the science of underwater adhesion, challenges posed by water, adhesive mechanisms of marine creatures, synthetic underwater adhesives, and potential applications and challenges in the field. The primary objective of this review is to inspire and facilitate the development of innovative synthetic underwater adhesives while enhancing our understanding of the factors influencing underwater adhesion.[4]
Key Points:
An adhesive material's strength on a surface is determined by its bulk cohesive strength, as well as the bonds formed on the interface. As most glues are fluids, the rate of interfacial bond formation between the adhesive and the surface is dependent on how the fluid spreads, and the cohesive strength of the adhesive is dependent on the rate at which the adhesive peels off the surface. Specifically, an empirical relationship has been established by Gent that describes adhesive work as a function of interfacial bonds (thermodynamic work) and the rate of peeling.[4]
While a wide variety of adhesives with specific applications are manufactured globally, most of these adhesives exhibit decreased efficacy in moist or submerged environments. This loss of adhesive properties can be ascribed to four mechanisms:[4]
First, the mussel foot's distal region forms a cavity with negative pressure in proximity to the substrate. Next, it manages the chemical conditions within the void by controlling factors like pH, ionic strength, and redox potential. Subsequently, partially soluble proteins, known as coacervates, are secreted. These coacervates later undergo a phase inversion between water and protein. Following this, the mussel foot constructs a coating based on Mfp-1 over the phase-inverted immature byssal thread. This coating then solidifies through mineral and enzyme-assisted crosslinking reactions, resulting in the formation of mature adhesive byssal threads.[4]
The adhesive used by sandcastle worms involves a complex process. Initially, the glue precursors are rich in cationic and anionic groups, and a condensation reaction occurs at the paddle-shaped cilia on the worm's building organ. This reaction leads to the formation of a complex coacervate phase, which is a critical step in the initial adhesion of sandcastle worm structures.[4]
Unlike Mfp-3s, where coacervation is driven by enthalpic interactions between oppositely charged macromolecules, in the sandcastle worm adhesive, the driving force is electrostatic interactions between weak polyelectrolytes like polyphosphate and polylysine. This complex coacervation process results in the creation of a water-immiscible dense phase that can be used as an underwater adhesive.[4]
The sandcastle worm adhesive undergoes a two-step curing process for permanent adhesion. In the first step, the complex coacervate reacts with divalent ions and responds to pH differences between the secretory system and seawater, solidifying rapidly once applied underwater. In the second step, DOPA units in the adhesive are oxidized by catechol oxidase, leading to a phase transition of the glue and the formation of a tough, leathery, brownish solid. The combination of interfacial wetting properties from the complex coacervation and cohesive strength from the two-step solidification process makes the sandcastle worm adhesive effective for underwater applications.[4]
Hydrophobicity
Hygroscopicity and Swelling Property
Solvent Exchange
Special Functional Groups
Structural Underwater Adhesives
Strategies for Enhancing Cohesion of Underwater Adhesives
Common Methods of Binding in Bio-materials[6]
Underwater adhesives can be categorized into two major types: glue-type and tape-type
Monomer Solutions[6]
Hydrophilic adhesive systems pose a more significant challenge than their hydrophobic counterparts in terms of removing the hydration layer. Recent advancements in mussel-inspired catechol chemistry have introduced a novel approach for underwater adhesives, leveraging the strong bonding capabilities of catechol groups in aqueous environments. Scientists have drawn inspiration from mussel foot proteins (mfps) to create a hydrogel composite glue. Their approach involved coating substrates with a dopamine-Fe-Tris solution and injecting an alginate (Alg) solution in between, subsequently pressing the substrates together. This sandwich-like structure enabled dopamine to auto-oxidize into polydopamine, which could coat various surfaces and induce interfacial adhesion. Additionally, Fe3+ ions bridged polydopamine and the interdiffusion alginate by forming coordination bonds between the catechol group of dopamine and the carboxylate group of alginate, ensuring robust cohesion. While these adhesives exhibited impressive underwater adhesion strengths of up to 400 kPa, the bonding process presented challenges in terms of control. To address this issue, the authors refined the adhesives by introducing glycerol as a dispersant for alginate, dopamine, Tris, and ferric salts. The high-viscosity glycerol glue, when applied underwater, allowed water and glycerol to interdiffuse, causing the components to dissolve and interact, ultimately forming a gel.
Polymer Solutions[6]
Apart from catechol-based monomers, underwater adhesives can also be created using polyphenolic polymers. This is often achieved by incorporating catechol or gallol groups into the polymer chains through copolymerization or post-modification. The copolymers developed using this approach tend to be water-immiscible. Consequently, these adhesives are composed of polymers and organic solvents, with chloroform or dichloromethane being frequently employed due to their higher density compared to water.
In comparison to dopamine-based monomer adhesive systems, which have less clarity regarding their polymerization process and final structures, polymers containing catechol or gallol groups offer well-defined chemical structures and molecular weights. This makes them valuable not only for developing underwater adhesives but also for studying the adhesion mechanism by examining the relationship between polymer properties and adhesion strength. Their findings revealed that catechol-based polymers with either cationic or anionic groups exhibited stronger underwater adhesion compared to control polymers lacking ionic groups. It is suggested that charged groups can interact with metallic surfaces through ionic, coordinate, or hydrogen bonding, generally enhancing adhesion. However, it is crucial to carefully adjust the amount of charged groups, as an excessively high charge density can diminish adhesion.
Polymer Melts[6]
In recent years, there has been growing interest in solvent-free polymer melt-based underwater adhesives due to concerns about the potential harm posed by organic solvents commonly found in polymer glues. The formulation of effective adhesives requires low-viscosity polymer melts to ensure good spreadability. However, a decrease in viscosity can lead to reduced cohesive strength, resulting in weaker adhesion. To address this challenge, a common approach involves incorporating cross-linkable components into low-glass transition temperature (Tg) polymers. Additionally, there are two distinct strategies employed to achieve surface dehydration: enhancing the hydrophobic nature of the polymer to disrupt the hydration layer and utilizing polymer hydrophilicity to absorb interfacial water.
Coacervate[6]
A coacervate can be described as a liquid phase composed of a concentrated polymer-rich region in equilibrium with a more dilute phase. The formation of a coacervate arises from the liquid-liquid phase separation within a solution. This separation process is driven by various molecular interactions, including electrostatic attractions between oppositely charged polyelectrolytes, interactions between cationic polyelectrolytes and multivalent anions, coordinate bonding, hydrogen bonding, hydrophobic forces, and cation-π interactions. Coacervates exhibit distinct characteristics such as high polymer concentration, low viscosity, rapid diffusivity, and minimal interfacial tension. Nature has harnessed coacervation in the production of adhesive proteins by organisms like sandcastle worms and mussels, allowing them to achieve strong underwater adhesion in seawater. Drawing inspiration from this, researchers have developed a range of coacervate-based underwater adhesives in recent years due to the advantageous properties that coacervates offer for underwater adhesion.
Tape-Type Underwater Adhesive[6]
Tape-type underwater adhesives, unlike their glue-type counterparts, are pliable solid materials designed to adhere directly to substrates in aquatic environments. Achieving robust underwater adhesion with tape-type adhesives presents a greater challenge for two primary reasons. First, disrupting the hydration layer at the joint interface is inherently more complex for solid materials in comparison to molecule-based liquid glues. Second, soft interfaces can readily trap water droplets, leading to a reduction in the effective contact area and the introduction of potential crack defects. To address these challenges, various strategies have been proposed to enhance the underwater performance of tape-type adhesives.
Tape-type adhesives can be categorized into two main groups based on their bonding mechanisms: molecular interaction-based adhesives and physical suction-based adhesives. The former relies on molecular interactions occurring at the adhesive-substrate interface, while the latter employs microstructures that facilitate water drainage and create adhesion through a suction effect driven by capillarity. The production of tape-type adhesives centered around molecular interactions is relatively straightforward; however, they tend to exhibit lower adhesion strengths, particularly in hydrophilic polymer systems. On the other hand, physical suction-based adhesives generally excel in terms of underwater adhesion, repeatability, and preventing chemical contamination of adhered surfaces. Nevertheless, they often necessitate intricate structural designs, and complex manufacturing processes, and are challenging to produce at scale. These can include polymer coatings, plastic films, elastomers, and hydrogels.
Electrostatic interaction serves as a frequently employed approach for achieving underwater adhesion. Nonetheless, it is important to note that electrostatic interactions tend to weaken in environments with elevated salt concentrations, such as seawater, primarily due to the Debye screening effect.
To summarize, tape-type underwater adhesives typically exhibit weaker adhesive strength compared to glue-type counterparts due to challenges associated with poor interfacial contact. For molecular interaction-based tape-type adhesives, addressing the issue of water layer removal remains a significant obstacle. Although progress has been made at the molecular level by enhancing the surface hydrophobicity of these adhesives, efficiently draining interfacial water at a macroscopic scale, especially for large-area adhesion, remains a formidable challenge that is often overlooked. Furthermore, the increased surface hydrophobicity of adhesives introduces a new complication, as it tends to favor hydrophobic substrates over hydrophilic ones. Consequently, the primary research challenges in this domain involve enhancing interfacial interactions and implementing effective water drainage mechanisms.
Wound healing is a complex and vital process for restoring the skin's barrier function. However, various diseases can disrupt this process, leading to chronic wounds that pose a significant medical challenge. These wounds deviate from the usual healing stages and are often complicated by a pro-inflammatory environment, characterized by increased proteinases, hypoxia, and bacterial accumulation.
Effectively treating chronic wounds remains a significant unmet medical need due to the complex symptoms arising from disruptions in the wound microenvironment's metabolism. Consequently, advanced medical devices, including wound dressings, wearable wound monitors, negative pressure wound therapy devices, and surgical sutures, have been developed to address these issues and promote skin tissue regeneration.
These medical devices encompass a wide array of products, utilizing both natural materials like chitosan, keratin, casein, collagen, hyaluronic acid, alginate, and silk fibroin, as well as synthetic polymers such as polyvinyl alcohol, polyethylene glycol, poly(lactic-co-glycolic acid), polycaprolactone, and polylactic acid. Additionally, they may incorporate bioactive substances like chemical drugs, silver, growth factors, stem cells, and plant compounds.
Wounds are typically categorized based on their depth and the affected skin layers. Superficial wounds involve only the epidermal layer, while partial-thickness wounds affect deeper dermal layers. Full-thickness wounds extend even further, reaching subcutaneous fat and deeper tissues. Burns, a common type of skin injury, are classified as first-, second-, third-, and fourth-degree burns based on the severity, ranging from superficial to deep, with the most severe involving damage to underlying tissues, nerves, muscles, tendons, and bone.
Wound healing involves four main phases: hemostasis, inflammation, proliferation, and remodeling. Hemostasis initiates blood clot formation and vasoconstriction, followed by the release of proinflammatory cytokines and growth factors. Inflammation involves the recruitment of immune cells like macrophages, neutrophils, and lymphocytes, while angiogenesis and re-epithelialization occur due to the proliferation of fibroblasts and keratinocytes. Eventually, fibroblasts differentiate into myofibroblasts, leading to extracellular matrix deposition and tissue remodeling. These processes are orchestrated by various cells, enzymes, cytokines, proteins, and hormones in the body.
Wounds occur when the skin's epidermal layer is broken, leading to injuries that can range from superficial to full-thickness, as well as burns categorized into degrees based on severity. The wound healing process comprises phases like hemostasis, inflammation, proliferation, and remodeling, involving various cells, cytokines, and growth factors.
During the healing process, the wound initially forms a blood clot for reinforcement, followed by the release of molecules like serotonin, histamine, and growth factors that promote cell proliferation, migration, and angiogenesis. The immune system is also engaged, recruiting neutrophils, monocytes, and macrophages to remove bacteria and facilitate the healing process.
After a few days, macrophages take over from neutrophils, and fibroblasts begin to proliferate and deposit collagen fibers. Over time, the collagen fibers mature, and the wound contracts, often assisted by myofibroblasts. This remodeling phase is continuous and can persist for the patient's lifetime.
There are two primary wound categories: acute and chronic. Acute wounds generally heal within 2-3 weeks, while chronic wounds persist for 6-8 weeks or longer and may lead to complications like ulcers. Chronic wounds can result from diseases like diabetes and fail to follow the typical healing phases.
The transition from pro-inflammatory M1 macrophages to tissue-repairing M2 macrophages is crucial for wound healing. Impaired transition may lead to chronic wounds, as seen in venous ulcers and diabetic wounds. Wounds in diabetic patients often stall in the inflammatory phase due to factors like infection and necrotic tissue, leading to persistent inflammation.
Chronic wounds, especially in diabetic individuals, pose severe health and economic burdens, and can even result in amputations in the worst cases. Research on effective wound dressings is vital to address this critical medical issue.
The presence of microorganisms like bacteria and fungi can lead to infections in wounded areas, particularly when host immune systems are weakened. Common bacterial sources that cause delayed wound healing include Streptococcus pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa, and certain Clostridium species. Other factors contributing to wound infections include hypoxia, ischemia, and immune deficiencies.
Neglected wound care can eventually lead to life-threatening conditions like bacteremia and septicemia. While microorganisms may multiply on the wound's surface in healthy individuals without triggering clinical symptoms, invasion of the living host tissues can lead to a series of local and systematic responses, causing purulent discharge, symptomatic cellulitis, and further soft tissue injury. Bacterial biofilms play a role in delaying wound healing, particularly in burn wounds.
Chronic wounds are more susceptible to infection than acute wounds, mainly due to impaired leukocyte migration and weakened phagocytosis in the presence of a high microbial load.
Pain management is essential for patients' recovery, as excessive pain can hinder the healing process and lead to physical and mental burdens. There are two main types of wound pain: nociceptive pain, a natural response to tissue damage, and neuropathic pain, associated with nerve damage. Effective pain management is crucial for patient comfort and quality of life, and wound dressings can play a role in reducing pain by lowering the bacterial load and inflammatory reactions in the nervous system.
Primary hyperalgesia, characterized by heightened sensitivity due to inflammation or repeated stimuli, may be treated with a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and mild opioids. Topical drug delivery to the wound site, particularly using ibuprofen, has been studied for its local pain reduction effects. Ibuprofen-loaded foam dressings have been found to provide significant pain relief, making them a safer alternative to systemic pain treatment.
Natural polymers are gaining popularity in the production of wound dressings due to their biodegradability, biocompatibility, and unique properties. Some of these natural polymers include chitosan, keratin, casein, collagen, and hyaluronic acid.
Chitosan, known for its positive charge, enhances drug absorption and can be applied as a coating layer on particle surfaces. It has the potential to control drug-release behavior. Chitosan-based products, such as hydrogels and nanofibers, are used in wound healing, and they exhibit antibacterial properties.
Keratin, abundant in human and animal parts, is biocompatible and biodegradable. It has been utilized in various wound dressings, such as films, hydrogels, and scaffolds, to support tissue regeneration and facilitate the wound-healing process.
Casein, a milk-derived protein, has self-assembling properties and can be combined with synthetic polymers to enable electrospinning. Casein-based products, including electrospun nanofibrous mats and injectable hydrogels, have been developed to promote wound healing, blood clotting, and hemostasis.
Collagen, as a key component of the extracellular matrix (ECM), provides tensile strength to the skin and has antibacterial properties. Collagen-based wound dressings stimulate granulation tissue formation, angiogenesis, and collagen fiber deposition, enhancing dermal and epidermal wound repair.
Hyaluronic acid, found in connective tissues, supports organ functions and retains moisture on wound surfaces, preventing dryness and promoting faster healing. It is incorporated into foams or creams for topical drug delivery, and some commercial products containing hyaluronic acid have shown positive outcomes in wound repair and pain management.
Sodium alginate, a natural polysaccharide extracted from brown algae, is widely used in wound management and tissue engineering due to its biocompatibility, bio-absorbability, and gel-forming ability. When preparing hydrogels from alginate solutions, an ionic crosslinking agent is added, forming an "egg-box" structure that influences the characteristics of the gels. Other studies have incorporated alginate into hydrogels, nanofibers, and membranes, sometimes combined with substances like honey, to promote antioxidant properties, tissue regeneration, and burn wound healing.
Silk fibroin, derived from various insects, is a biocompatible and biodegradable material with excellent mechanical properties. It has been widely studied for tissue regeneration, including in skin, vascular, cartilage, bone, tendon, and ligament applications. Silk fibroin is used in various forms, such as hydrogels, films, fibers, and sponges, to enhance collagen synthesis and re-epithelialization, thus promoting wound healing. Researchers have developed innovative silk fibroin-based dressings with temperature-sensing capabilities and wound-healing properties. Some of these dressings have been reinforced with nanodiamonds to improve thermal stability, and they exhibited biocompatibility and rapid wound closure rates in animal studies. Another study involved a multilayer membrane with silk fibroin, chitosan, and alginate, providing controlled drug-release properties without compromising mechanical strength.
Several synthetic polymers are widely used in wound dressings due to their high biocompatibility and hydrophilicity. Commonly employed synthetic polymers include polyvinyl alcohol (PVA), polyethylene glycol (PEG), polylactic acid (PLA), poly(lactic‐co‐glycolic acid) (PLGA), and polycaprolactone (PCL). These polymers create a moist wound environment, prevent the accumulation of exudates, and degrade into non-toxic products. They are also adhesive and maintain mechanical strength in tissues.
Polyvinyl alcohol (PVA) is known for its biocompatibility and has been crosslinked with chemicals like glutaraldehyde to enhance stability. Research has focused on combining PVA with other materials such as chitosan, starch, or silk protein sericin to create wound dressings with high cell viability, antibacterial properties, and accelerated wound healing.
Polyethylene glycol (PEG) is an FDA-approved, non-toxic polymer used in wound dressings. PEG blended with polylactic acid (PLA) has been developed to create dressings with anti-inflammatory properties and better healing outcomes. PEG/chitosan hydrogels with silver nanoparticles have also been shown to accelerate wound healing, making them a promising material for chronic diabetic wounds.
Polycaprolactone (PCL) offers good biocompatibility, biodegradability, and mechanical strength. Researchers have combined PCL with chitosan, curcumin, insulin-loaded chitosan nanoparticles, and other substances to create dressings that enhance wound healing in both in vitro and in vivo studies.
Polylactic acid (PLA) is another biocompatible and biodegradable polymer often used in tissue engineering and biomedical applications. Blending PLA with other polymers or additives can address its limitations, such as slow degradation and low mechanical strength, to improve its suitability for wound dressings. Core-shell structured nanofibers of PLA and Poly(γ‐glutamic acid) (γ‐PGA) have shown potential in promoting wound healing by enhancing cell proliferation and re-epithelialization in animal models.
Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible and biodegradable copolymer, and its properties can be adjusted by altering the ratio of lactic acid and glycolic acid monomers. Studies have utilized PLGA to accelerate angiogenesis and enhance wound healing. PLGA/gelatin ratios have also been electrospun to create scaffolds suitable for chronic wound treatment, although further research is needed to validate their effectiveness.
Wound dressings fall into several categories: biological dressings (temporary), conventional dressings (temporary), biosynthetic dressings (mimic natural skin), and antimicrobial dressings (contain agents like silver, cadexomer iodine, or honey). Biological and conventional dressings are used temporarily. Biosynthetic dressings like Biobrane® can mimic natural skin and replace damaged skin layers. Antimicrobial dressings, particularly those with silver compounds, have been effective in reducing infection risk, such as in burn wound treatment.
Hydrogels are swellable dressings composed of biocompatible and biodegradable materials, primarily polyvinylpyrrolidone (PVP) and methacrylate. These hydrogels consist of 80-90% water, maintaining a moist wound environment through water release. They are non-toxic, non-adherent, and flexible, making them suitable for wounds with unconventional shapes and edges. Recent studies have explored various hydrogel formulations for wound healing. However, one of the main issues with hydrogel is their low mechanical properties which correlate to the plasticising effect of water in the polymer network.
Numerous natural and synthetic polymers have been tested for creating biodegradable electrospun nanofibers. Collagen scaffolds closely mimic natural skin, promoting cell growth and ECM penetration. Scaffolds made from a single polymer create a "fishnet effect," reducing cell penetration. Natural polymers enhance cell adhesion and growth, while synthetic polymers provide mechanical strength. Therefore, a combination of both types of polymers is often used.
Nanofiber mats composed of PLGA/silk fibroin and loaded with zinc oxide nanoparticles exhibit mild antioxidant activity and effectively combat both gram-positive and gram-negative bacteria. In vivo studies suggest their potential for treating chronic wounds. Additionally, incorporating different molecular weights and amounts of PEG into PLA, along with encapsulating curcumin as a model drug, shows promise in drug release and suitability as wound dressings.
A vital wound healing tool is the surgical suture, which can be designed to expedite the wound healing process. Sutures are medical devices composed of natural or synthetic polymers, serving to impart mechanical support and secure tissues during surgical procedures. Despite the long-standing history of sutures in wound care, they, along with staples, tape, and adhesives, remain the most prevalent medical devices employed in surgical contexts.
In 1996, Human Rights Watch released a report that exposed bonded child labor in seven different sectors in India, including the silk industry. This update provides insights into the situation since the 1996 report, focusing mainly on the silk sector. It draws on interviews with more than 155 individuals and field investigations conducted in three Indian states. Approximately 350,000 children, who toil for 12 hours a day, seven days a week, are engaged in the production of silk thread, enduring physical and verbal abuse.
The report consists of seven sections. The first section offers a summary, outlining the investigation's scope and methodology. The second section presents recommendations aimed at eradicating bonded child labor, directed at the Indian government, state governments, the international community, and various stakeholders. The third section provides background information about bonded child labor in India, defining a bonded child as one compelled to work under servitude to repay a debt, effectively becoming a commodity exchanged between parents and employers. It also discusses the Indian silk industry and government support.
The fourth section delves into the issue of bonded child labor within the Indian silk industry, where children are primarily involved in silk thread production and sari weaving. Testimonials from these children reveal instances of physical, verbal, and sexual abuse by their employers. The fifth section explores caste-based discrimination and its implications for bonded labor, highlighting that most bonded laborers are from low-caste backgrounds, are illiterate, and live in extreme poverty. This traditional discrimination has kept the plight of bonded children concealed.
The sixth section scrutinizes the role of the Indian government in protecting bonded child laborers, and identifying loopholes and barriers to enforcing child labor laws. The report contends that not enough has been done to support these children. The seventh section analyzes the legal framework concerning child labor, encompassing international and Indian laws, as well as the right to education.
The global waterproof adhesives and sealants market is poised for substantial growth in the coming years. According to Statista, the global adhesive market was valued at $43.75 billion in 2020 and is projected to reach $64.71 billion by 2027, driven by increasing population and industry trends. Key growth sectors include automobiles, construction, healthcare, aerospace, logistics, and electronics, all of which rely on adhesives for various applications. This broad sector demand is expected to contribute to global market growth in the foreseeable future.
The expanding infrastructure sector, which accounts for a significant portion of adhesive consumption, is a major driver of market expansion. The construction market, with a size of $6.4 trillion in 2020, is projected to reach $14.4 trillion by 2030, further influencing adhesive market growth.
In addition, the adhesive market is influenced by growing manufacturing industries, as adhesives and sealants provide solutions for heat resistance, vibration, sealing, and bonding. The global automotive industry is expected to reach $3.8 trillion in auto sales by 2030, contributing to the growth of the manufacturing sector. Government initiatives, such as Free Trade Agreements between countries, are lowering production costs and affecting market growth. Packaging industries, construction infrastructure, automotive markets, and packaging industries are expected to play a pivotal role in driving the adhesive market's growth.
Environmental concerns are also impacting the industry, with a focus on reducing volatile organic compounds (VOCs) in adhesive products. Technological changes and supply chain disruptions are challenges the industry faces. Merger and acquisition activities are helping companies access new markets and technologies, fostering growth. New technologies, such as UV and silicon-based adhesives, contribute to market expansion.
In summary, the global waterproof adhesives and sealants market is expected to grow significantly, fueled by demand from various sectors, expanding infrastructure, and technological advancements, while environmental and supply chain issues remain challenges to address.