Sandcastle Worm Research Articles

Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation

Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe3+ from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time (> 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.

An Overview on the Adhesion Mechanisms of Typical Aquatic Organisms and the Applications of Biomimetic Adhesives in Aquatic Environments.

Water molecules pose a significant obstacle to conventional adhesive materials. Nevertheless, some marine organisms can secrete bioadhesives with remarkable adhesion properties. For instance, mussels resist sea waves using byssal threads, sandcastle worms secrete sandcastle glue to construct shelters, and barnacles adhere to various surfaces using their barnacle cement. This work initially elucidates the process of underwater adhesion and the microstructure of bioadhesives in these three exemplary marine organisms. The formation of bioadhesive microstructures is intimately related to the aquatic environment. Subsequently, the adhesion mechanisms employed by mussel byssal threads, sandcastle glue, and barnacle cement are demonstrated at the molecular level. The comprehension of adhesion mechanisms has promoted various biomimetic adhesive systems: DOPA-based biomimetic adhesives inspired by the chemical composition of mussel byssal proteins; polyelectrolyte hydrogels enlightened by sandcastle glue and phase transitions; and novel biomimetic adhesives derived from the multiple interactions and nanofiber-like structures within barnacle cement. Underwater biomimetic adhesion continues to encounter multifaceted challenges despite notable advancements. Hence, this work examines the current challenges confronting underwater biomimetic adhesion in the last part, which provides novel perspectives and directions for future research.

Bioinspired Printable Tough Adhesives with In Situ Benignly Triggered Mechanical Enhancements

AbstractAdhesives can intimately connect humans to machines, seamlessly bond diverse tissues in the human body, and manage various diseases. However, the precise spatial control of wet and tough adhesion of biocompatible hydrogels on biological tissues remains a major challenge. Inspired by the bioglue secreted by sandcastle worms, the design of printable tough adhesives (PTAs) is proposed, a supramolecular hydrogel that can be printed into defined structures, in situ mechanically reinforced into a tough matrix with physiologically relevant benign triggers, and strongly adhere to diverse substrates. With carefully selected polymer components and ratios, it is discovered that the 3D printed PTAs can achieve a marked increase in toughness, tensile strength, and stiffness after being immersed in water/saline solution or attached to biological tissues. To assess the robust toughening mechanism triggered by the supramolecular interactions, the effects of polymer content and pH on the mechanical performance of PTAs and the kinetics of their triggered reinforcement are thoroughly investigated. The potential of PTAs is further demonstrated for manufacturing tough connective tissue mimetics, controlling patterned bioadhesion, and designing programmable 4D soft robotics. The bioinspired, printable, benignly triggerable, and adhesive supramolecular PTAs are expected to find broad applications in engineering and medicine.

Engineering Wet-Resistant and Osteogenic Nanocomposite Adhesive to Control Bleeding and Infection after Median Sternotomy.

Median sternotomy surgery stands as one of the prevailing strategies in cardiac surgery. In this study, the cutting-edge bone adhesive is designed, inspired by the impressive adhesive properties found in mussels and sandcastle worms. This work has created an osteogenic nanocomposite coacervate adhesive by integrating a cellulose-polyphosphodopamide interpenetrating network, quaternized chitosan, and zinc, gallium-doped hydroxyapatite nanoparticles. This adhesive is characterized by robust catechol-metal coordination which effectively adheres to both hard and soft tissues with a maximum adhesive strength of 900 ± 38kPa on the sheep sternum bone, surpassing that of commercial bone adhesives. The release of zinc and gallium cations from nanocomposite adhesives and quaternized chitosan matrix imparts remarkable antibacterial properties and promotes rapid blood coagulation, in vitro and ex vivo. It is also proved that this nanocomposite adhesive exhibits significant in vitro bioactivity, stable degradability, biocompatibility, and osteogenic ability. Furthermore, the capacity of nanocomposite coacervate to adhere to bone tissue and support osteogenesis contributes to the successful healing of a sternum bone defect in a rabbit model in vivo. In summary, these nanocomposite coacervate adhesives with promising characteristics are expected to provide solutions to clinical issues faced during median sternotomy surgery.

Clinical Use of a Mineral-Organic Resorbable Bone Adhesive: A First Human Case Report with a 3-Year Follow-up.

The ability for clinicians to adequately obtain primary stability in host bone is critical to the success of dental implants. Numerous conditions require dentists to perform multistage approaches to rebuild deficient bone volume prior to surgically placing implants. In many instances, implant placement cannot be achieved due to a lack of primary implant stability. Recently, a novel mineral-organic resorbable bone adhesive (MORBA) has demonstrated promising results in animal studies. MORBA is a synthetic, injectable, self-setting, load-bearing adhesive biomaterial that exhibits osteopromotive properties and bonds bone to bone and metal within 10 minutes and can fully resorb in 30 weeks. Its unique novel formulation was developed from biomimetic proteins found in marine animal creatures that possess distinct adhesive properties underwater. Excellent long-term results have shown its potential use for achieving primary stability in immediate implants. The present case report demonstrates the first use of MORBA in a human patient, utilized on a nonrestorable mandibular first molar. MORBA was utilized after placement of a mobile 5.8-mm implant to achieve stabilization. At 3 months postsurgery, both clinical and CBCT evaluations showed maintained implant stability. One year after implant placement, radiographic bone was seen on the buccal surface of the implant with continued long-term stabilization. This case report extends to 3 years whereby the use of MORBA, in an initially unstable situation, demonstrated an excellent long-term follow-up. MORBA provided immediate implant stability with resorbable characteristics, leading to successful long-term clinical outcomes up to 3 years. This innovative biomaterial offers a more efficient solution to a critical problem in implant dentistry, allowing optimal primary stability during immediate implant placement, thus reducing treatment times and costs.

Incorporating amphiphilic modifier into PVDF membrane through in-situ electrostatic crosslinking for efficient oil-water separation

Constructing stable amphiphilic membrane surfaces in a facile and controlled way is highly desired for fabrication of antifouling water purification membranes. Herein, inspired by adhesives of sandcastle worms, we proposed an in-situ electrostatic crosslinking method to incorporate amphiphilic modifiers into poly (vinylidene fluoride) membranes. Pluronic F127 grafted with positively charged quaternary ammonium groups are added into the casting solution, while perfluorosulfonic acid bearing negatively charged sulfonic acid groups and perfluorocarbon chains are dissolved in the coagulation bath. During non-solvent induced phase separation process, electrostatic crosslinking between quaternary ammonium and sulfonic acid led to the in-situ formation of amphiphilic modifiers on membrane surfaces and pore walls. The resulting membrane exhibits high water permeance up to 625 Lm−2h−1 bar−1 and superior antifouling performance with total flux decline ratio of 2 % and flux recovery ratio of 99.3 % for oil-water separation. Besides, the membrane displays excellent structural stability and self-cleaning properties against highly viscous crude oils.

Bioinspired by Sandcastle Worm Glue: An Underwater Reversible Adhesive Modulated by pH Environments Based on Urushiol

Bioinspired by Sandcastle Worm Glue: An Underwater Reversible Adhesive Modulated by pH Environments Based on Urushiol

Photo-/electro-chromic underwater adhesive coacervate from self-assembly of zwitterions and polyoxometalate

Wet/underwater adhesion is a matter of common occurrence to some marine organisms, but it is a quite thorny problem in practical engineering field and even in our daily lives. Meanwhile, preparation of an instantly available underwater adhesive with good adhesion strength is another great challenge. Herein, inspired by the oppositely charged polyelectrolytes coacervate of sandcastle worm glue, a zwitterion-based self-assembled underwater adhesive coacervate is reported. This coacervate can be deployed in real-time by mixing together of zwitterionic poly (HEMA-co-SBMA) (PHS), silicotungstic acid (STA) and arginine (Arg). It is an entirely new construction strategy via synergistical self-assembly of low- and high-molecular-weight zwitterions and polyanions by electrostatic force. The coacervate plays well in underwater adhesion to substrates such as organic plastic and inorganic ceramic. It also achieves outstanding performance in dry substrates, due to multiple interactions formed at the interface of adhesive coacervate and substrate. Moreover, this coacervate shows underwater sealing property and resistance to violent water flush. Additionally, the coacervate possesses electro/photo-chromic properties that may achieve stimuli-responsive color switching, therefore broadening its potential applications for external signals responsive devices like energy-efficient windows, wearable electronics, and warning devices.

Bio‐inspired Protein‐Based and Activatable Adhesion Systems

AbstractAdhesives are in general chemically or physically sticky substances used to join surfaces. In case of gluing biological and living substrates, there is a need for bioadhesives that meet requirements such as biocompatibility, non‐toxicity, and degradability. Inspiration for bioadhesives is found in nature, where distinct mussels, sandcastle worms, barnacles, caddisfly larvae, spiders, and glowworms amongst others, use mainly protein‐based glues for various purposes. There is a great selection of reviews and books covering the use of various bioadhesives in various applications, but here the focus lies on advances in the development of bio‐inspired protein‐based adhesives for biomedical applications.

Designing Bio-Inspired Wet Adhesives through Tunable Molecular Interactions

Marine organisms, such as mussels and sandcastle worms, can master rapid and robust adhesion in turbulent seawater, becoming leading archetypes for the design of underwater adhesives. The adhesive proteins secreted by the organisms are rich in catecholic amino acids along with ionic and amphiphilic moieties, which mediate the adaptive adhesion mainly through catechol chemistry and coacervation process. Catechol allows a broad range of molecular interactions both at the adhesive-substrate interface and within the adhesive matrix, while coacervation promotes the delivery and surface spreading of the adhesive proteins. These natural design principles have been translated to synthetic systems toward the development of biomimetic adhesives with water-resist adhesion and cohesion. This review provides an overview of the recent progress in bio-inspired wet adhesives, focusing on two aspects: (1) the elucidation of the versatile molecular interactions (e.g., electrostatic interactions, metal coordination, hydrogen bonding, and cation-π/anion-π interactions) used by natural adhesives, mainly through nanomechanical characterizations; and (2) the rational designs of wet adhesives based on these biomimetic strategies, which involve catechol-functionalized, coacervation-induced, and hydrogen bond-based approaches. The emerging applications (e.g., tissue glues, surgical implants, electrode binders) of the developed biomimetic adhesives in biomedical, energy, and environmental fields are also discussed, with future research directions proposed.

Biomimetic, self-coacervating adhesive with tough underwater adhesion for ultrafast hemostasis and infected wound healing.

Massive bleeding and wound infection due to severe traumas pose a huge threat to the life and health of sufferers; therefore, it is of clinical importance to fabricate adhesives with rapid hemostatic and superior antibacterial capabilities. However, the weak wet adhesion and insufficient function of existing bioadhesives limits their practical application. In this study, a sandcastle worm protein inspired polyelectrolyte self-coacervate adhesive of poly-γ-glutamic acid (PGA) and lysozyme (LZM) was developed. The adhesive exhibited strong underwater adhesion to various surfaces (>250 kPa for solid plates and >50 kPa for soft tissues) and maintained a 80 kPa even when soaked in water for 7 days. Rat liver and tail defect bleeding models revealed that the hemostatic efficiency was superior to that of commercial samples. The in vitro antimicrobial tests showed that the bacterial inhibition to Staphylococcus aureus and Escherichia coli reached almost 100%. Additionally, the infected wound regeneration model demonstrated that the healing rate of the adhesive group was about 100% within 15 days, which was greater than that of the control group. In vitro and in vivo experiments proved that this facilely prepared adhesive will be a promising material to fulfil the integration functions for rapid wound closure and facilitating wound healing.

Bio‐inspired functional coacervates

AbstractMany functional coacervates have been identified in biological systems, which have attracted widespread interest. Coacervation is a liquid–liquid phase separation (LLPS) process in which a macromolecule‐enriched liquid phase is formed together with a macromolecule‐depleted phase. Bio‐inspired coacervates possess excellent features such as underwater delivery, low interface energy, shear thinning, and excellent biocompatibility. They also serve as good delivery platforms for different types of molecules. In this review, we briefly discuss some important extracellular coacervate systems, including mussel adhesives, sandcastle worm glue, squid beak, and tropoelastin. We then provide an overview of the recent development of bio‐inspired functional coacervates for various biomedical applications, including medical adhesives, drug delivery, and tissue engineering. Bio‐inspired functional coacervates offer a promising material platform for developing new materials for biomedical applications.

Proanthocyanidins-loaded complex coacervates-based drug delivery attenuates oral squamous cell carcinoma cells metastatic potential through down-regulating the Akt signaling pathway.

Oral cancer, constituted up to 90% by squamous cell carcinomas, is a significant health burden globally. Grape seed proanthocyanidins (PA) have been suggested as a potential chemopreventive agent for oral cancer. However, their efficacy can be restricted due to the low bioavailability and bioaccessibility. Inspired by sandcastle worm adhesive, we adapted the concept of complex coacervation to generate a new type of drug delivery platform. Complex coacervates are a dense liquid phase formed by the associative separation of a mixture of oppositely charged polyelectrolytes, can serve as a drug delivery platform to protect labile cargo. In this study, we developed a complex coacervates-based delivery of PA. The release kinetics was measured, and anticancer effects were determined in two human tongue squamous cell carcinoma cell lines. The results showed that complex coacervate successfully formed and able to encapsulate PA. Additionally, PA were steadily released from the system in a pH-dependent manner. The drug delivery system could significantly inhibit the cell proliferation, migration, and invasion of cancer cells. Moreover, it could markedly reduce the expression of certain matrix metalloproteinases (MMP-2, 9, and 13) crucial to metastatic processes. We also found that suppression of protein kinase B (Akt) pathway might be the underlying mechanism for these anticancer activities. Taken together, complex coacervates-based delivery of PA can act as an effective anticancer approach for oral cancer therapy.

Adhesive Materials Inspired by Barnacle Underwater Adhesion: Biological Principles and Biomimetic Designs.

Wet adhesion technology has potential applications in various fields, especially in the biomedical field, yet it has not been completely mastered by humans. Many aquatic organisms (e.g., mussels, sandcastle worms, and barnacles) have evolved into wet adhesion specialists with excellent underwater adhesion abilities, and mimicking their adhesion principles to engineer artificial adhesive materials offers an important avenue to address the wet adhesion issue. The crustacean barnacle secretes a proteinaceous adhesive called barnacle cement, with which they firmly attach their bodies to almost any substrate underwater. Owing to the unique chemical composition, structural property, and adhesion mechanism, barnacle cement has attracted widespread research interest as a novel model for designing biomimetic adhesive materials, with significant progress being made. To further boost the development of barnacle cement–inspired adhesive materials (BCIAMs), it is necessary to systematically summarize their design strategies and research advances. However, no relevant reviews have been published yet. In this context, we presented a systematic review for the first time. First, we introduced the underwater adhesion principles of natural barnacle cement, which lay the basis for the design of BCIAMs. Subsequently, we classified the BCIAMs into three major categories according to the different design strategies and summarized their research advances in great detail. Finally, we discussed the research challenge and future trends of this field. We believe that this review can not only improve our understanding of the molecular mechanism of barnacle underwater adhesion but also accelerate the development of barnacle-inspired wet adhesion technology.

Bioinspired Sandcastle Worm-Derived Peptide-Based Hybrid Hydrogel for Promoting the Formation of Liver Spheroids.

The generation of hepatic spheroids is beneficial for a variety of potential applications, including drug development, disease modeling, transplantation, and regenerative medicine. Natural hydrogels are obtained from tissues and have been widely used to promote the growth, differentiation, and retention of specific functionalities of hepatocytes. However, relying on natural hydrogels for the generation of hepatic spheroids, which have batch to batch variations, may in turn limit the previously mentioned potential applications. For this reason, we researched a way to establish a three-dimensional (3D) culture system that more closely mimics the interaction between hepatocytes and their surrounding microenvironments, thereby potentially offering a more promising and suitable system for drug development, disease modeling, transplantation, and regenerative medicine. Here, we developed self-assembling and bioactive hybrid hydrogels to support the generation and growth of hepatic spheroids. Our hybrid hydrogels (PC4/Cultrex) inspired by the sandcastle worm, an Arg-Gly-Asp (RGD) cell adhesion sequence, and bioactive molecules derived from Cultrex BME (Basement Membrane Extract). By performing optimizations to the design, the PC4/Cultrex hybrid hydrogels can enhance HepG2 cells to form spheroids and express their molecular signatures (e.g., Cyp3A4, Cyp7a1, A1at, Afp, Ck7, Ck1, and E-cad). Our study demonstrated that this hybrid hydrogel system offers potential advantages for hepatocytes in proliferating, differentiating, and self-organizing to form hepatic spheroids in a more controllable and reproducible manner. In addition, it is a versatile and cost-effective method for 3D tissue cultures in mass quantities. Importantly, we demonstrate that it is feasible to adapt a bioinspired approach to design biomaterials for 3D culture systems, which accelerates the design of novel peptide structures and broadens our research choices on peptide-based hydrogels.

A sandcastle worm-inspired strategy to functionalize wet hydrogels

Hydrogels have been extensively used in many fields. Current synthesis of functional hydrogels requires incorporation of functional molecules either before or during gelation via the pre-organized reactive site along the polymer chains within hydrogels, which is tedious for polymer synthesis and not flexible for different types of hydrogels. Inspired by sandcastle worm, we develop a simple one-step strategy to functionalize wet hydrogels using molecules bearing an adhesive dibutylamine-DOPA-lysine-DOPA tripeptide. This tripeptide can be easily modified with various functional groups to initiate diverse types of polymerizations and provide functional polymers with a terminal adhesive tripeptide. Such functional molecules enable direct modification of wet hydrogels to acquire biological functions such as antimicrobial, cell adhesion and wound repair. The strategy has a tunable functionalization degree and a stable attachment of functional molecules, which provides a tool for direct and convenient modification of wet hydrogels to provide them with diverse functions and applications.

Bioengineered Protein-based Adhesives for Biomedical Applications.

Protein-based adhesives with their robust adhesion performance and excellent biocompatibility have been extensively explored over years. In particular, the unique adhesion behaviours of mussel and sandcastle worm inspired the development of synthetic adhesives. However, the chemical synthesized adhesives often demonstrate weak underwater adhesion performance and poor biocompatibility/biodegradability, limiting their further biomedical applications. In sharp contrast, genetically engineering endows the protein-based adhesives the ability to maintain underwater adhesion property as well as biocompatibility/biodegradability. Herein, we outline recent advances in the design and development of protein-based adhesives by genetic engineering. We summarize the fabrication and adhesion performance of elastin-like polypeptide-based adhesives, followed by mussel foot protein (mfp) based adhesives and other sources protein-based adhesives, such as, spider silk spidroin and suckerin. In addition, the biomedical applications of these bioengineered protein-based adhesives are presented. Finally, we give a brief summary and perspective on the future development of bioengineered protein-based adhesives.

Coacervate-Based Instant and Repeatable Underwater Adhesive with Anticancer and Antibacterial Properties.

Underwater adhesion is a great challenge for the development of adhesives as the attractive interfacial intermolecular interactions are usually weakened by the surface hydration layer. The coacervation process of sessile organisms like marine mussels and sandcastle worms has inspired substantial research interest in the fabrication of long-lasting underwater adhesives, but they generally suffer from time-consuming curing triggered by surrounding environmental changes and cannot reserve the adhesiveness once damaged. Herein, an instant and repeatable underwater adhesive was developed based on the coacervation of tannic acid (TA) and poly(ethylene glycol)77-b-poly(propylene glycol)29-b-poly(ethylene glycol)77 (PEG-PPG-PEG, F68), which was driven by hydrogen-bonding interaction, and the hydrophobic cores of F68 micelles offered an additional cross-linking to enhance the mechanical properties. The TA-F68 coacervates could be facilely painted on different substrates, exhibiting robust and instant underwater adhesion (with adhesion strength up to 1.1 MPa on porcine skin) and excellent repeatability (at least 1000 cycles), superior to the previously reported coacervates. Due to the biological activities of TA, the underwater adhesive displayed innate anticancer and antibacterial properties against different types of cancer cells and bacteria, showing great potential for diverse biomedical applications, such as injectable drug carriers, tissue glues, and wound dressings.

Fouling-resistant robust membranes via electrostatic complexation for water purification

Abstract Membrane-based separation provides an energetically efficient and environmentally benign solution to water purification. Biomimetic self-assembled membranes affording full-aqueous-phase membrane fabrication built on underwater bioadhesion create a new paradigm to green and controllable membrane fabrication, but currently are obstructed by fouling and stability hurdles. Inspired by the chemical features of charged cement proteins of sandcastle worm, we propose an electrostatic-driven complexation method to fabricate fouling-resistant robust membranes. Phosphorylated polyanion, quaternized polycation and perfluorinated sulfonic acid polyanion are successively assembled onto the porous substrate to obtain electrostatic-complexed fluorinated membranes (ECFMs), where quaternized cellulose serves as a bridging polyelectrolyte to induce and coordinate electrostatic complexation. Temporal complexation generates 84-nm-thick membranes with precisely controlled physicochemical structure, surface energy and spatial interaction with foulants, harvesting ultrahigh water permeance of 93.3 L m−2 h−1 bar−1 with organic dyes (>450 Da) removal over 90.0%, and high fouling resistance ensuring persistently high production of purified water. Unlike the amino protein of traditional bio-cement whose positive charge strongly relies on pH, the environmentally-independent chargeability of quaternary ammonium and hydrophobic fluorine segment synergistically renders the membranes superior adaptability towards various underwater conditions for dozens or hundreds of days.

Synthesis of novel copolymer/Mn+ biomimetic adhesives based on temperature strengthened coacervation effect

Synthesis of biomimetic adhesive for achieving robust interface bonding attracts numerous attentions for various applications. Inspired by the metal ions-assisted coacervation mechanism of sandcastle worm glue, novel copolymer/Mn+ complex wet adhesives are synthesized successfully, containing hydrophobic component, bidentate anionic component and temperature sensitive component. The anionic segments in copolymer interacts with different metal ions (Ca2+/Mg2+/Cu2+) in solution through coacervation reaction along with temperature-strengthened dehydration effect, resulting in the formation of biomimetic adhesives. The wet adhesion strength of the biomimetic adhesives is tunable based on the ions species, concentrations and coordination time, while the adhesion mechanisms are analyzed and discussed in details. The biomimetic adhesives not only can be used to tightly bond two solid surfaces underwater, but also is robust and effective in air. For example, current adhesives can firmly bonding various substrates including glass, Si, PTFE and animal bone. More importantly, the biomimetic adhesives are capable of sealing leaky pipes or vessels in harsh wet environment. Due to no dopamine chemistry, current adhesives involve no oxidation problem. We firmly believe this new system would demonstrate promising applications in surface engineering, wet sealing/repairing and tissue engineering.