Bioinspired Mineral–Organic Bone Adhesives for Stable Fracture Fixation and Accelerated Bone Regeneration

The use of hydrogel‐based bone adhesives has the potential to revolutionize the clinical treatment of bone repairs. However, severe deficiencies remain in current products, including cytotoxicity concerns, inappropriate mechanical strength, and poor fixation performance in wet biological environments. Inspired by the unique roles of glue molecules in the robust mechanical strength and fracture resistance of bone, a design strategy is proposed using novel mineral–organic bone adhesives for strong water‐resistant fixation and guided bone tissue regeneration. The system leveraged tannic acid (TA) as a phenolic glue molecule to spontaneously co‐assemble with silk fibroin (SF) and hydroxyapatite (HA) in order to fabricate the inorganic–organic hybrid hydrogel (named SF@TA@HA). The combination of the strong affinity between SF and TA along with sacrificial coordination bonds between TA and HA significantly improves the toughness and adhesion strength of the hydrogel by increasing the amount of energy dissipation at the nanoscale. This in turn facilitated adequate and stable fixation of bone fracture in wet biological environments. Furthermore, SF@TA@HA promotes the regeneration of bone defects at an early stage in vivo. This work presents a type of bioinspired bone adhesive that is able to provide stable fracture fixation and accelerated bone regeneration during the bone remodeling process.     

Physical Double‐Network Hydrogel Adhesives with Rapid Shape Adaptability,Fast Self‐Healing,Antioxidant and NIR/pH Stimulus‐Responsiveness for Multidrug‐Resistant Bacterial Infection and Removable Wound Dressing

Developing physical double‐network (DN) removable hydrogel adhesives with both high healing efficiency and photothermal antibacterial activities to cope with multidrug‐resistant bacterial infection, wound closure, and wound healing remains an ongoing challenge. An injectable physical DN self‐healing hydrogel adhesive under physiological conditions is designed to treat multidrug‐resistant bacteria infection and full‐thickness skin incision/defect repair. The hydrogel adhesive consists of catechol–Fe³⁺ coordination cross‐linked poly(glycerol sebacate)‐co‐poly(ethylene glycol)‐g‐catechol and quadruple hydrogen bonding cross‐linked ureido‐pyrimidinone modified gelatin. It possesses excellent anti‐oxidation, NIR/pH responsiveness, and shape adaptation. Additionally, the hydrogel presents rapid self‐healing, good tissue adhesion, degradability, photothermal antibacterial activity, and NIR irradiation and/or acidic solution washing‐assisted removability. In vivo experiments prove that the hydrogels have good hemostasis of skin trauma and high killing ratio for methicillin‐resistant staphylococcus aureus (MRSA) and achieve better wound closure and healing of skin incision than medical glue and surgical suture. In particular, they can significantly promote full‐thickness skin defect wound healing by regulating inflammation, accelerating collagen deposition, promoting granulation tissue formation, and vascularization. These on‐demand dissolvable and antioxidant physical double‐network hydrogel adhesives are excellent multifunctional dressings for treating in vivo MRSA infection, wound closure, and wound healing.     

TAPE: A Medical Adhesive Inspired by a Ubiquitous Compound in Plants

Adhesives play an important role in industrial fields such as electronics, architectures, energy plantation, and others. However, adhesives used for medical purpose are rather under‐developed compared with those used in industry and consumer products. One key property required for medical adhesives is to maintain their adhesiveness in the presence of body fluid. Here, an entirely new class of medical adhesives called TAPE is reported; this is produced by intermolecular hydrogen bonding between a well‐known polyphenol compound, tannic acid, and poly(ethylene glycol). The preparation method of TAPE is extremely easy, forming a few liters at once by just the simple mixing of the two compounds without any further chemical synthetic procedures. TAPE shows a 250% increase in adhesion strength compared with fibrin glue, and the adhesion is well maintained in aqueous environments. It is demonstrated that TAPE is an effective hemostatic material and a biodegradable patch for detecting gastroesophageal reflux disease in vivo. Widespread use of TAPE is anticipated in various medical and pharmaceutical applications such as muco‐adhesives, drug depots, and others, because of its scalability, adhesion, and facile preparation.     

A Bioinspired Medical Adhesive Derived from Skin Secretion of Andrias davidianus for Wound Healing

Existing surgical tissue adhesives on the market cannot meet the desired demand for clinical operations due to their limited adhesivity or undesired cytotoxicity. A new bioadhesive is derived from the skin secretion of Andrias davidianus (SSAD). This bioinspired SSAD has significantly stronger tissue adhesion than the fibrin glue and improved elasticity and biocompatibility when compared to the cyanoacrylate glue both ex vivo and in vivo. Additionally, the SSAD‐based adhesive decreases skin wound healing time and promotes wound regeneration and angiogenesis. The SSAD‐based adhesive is completely degradable, strongly adhesive, and easily produced from a renewable source. Based on these favorable properties, the SSAD‐based bioadhesive demonstrates potential as a surgical bioadhesive for a broad range of medical applications.     

Biomimetic Natural Biopolymer-Based Wet-Tissue Adhesive for Tough Adhesion,Seamless Sealed,Emergency/Nonpressing Hemostasis,and Promoted Wound Healing

Bioadhesives have been used in clinics among the most prospective alternatives to sutures and staples for wound sealing and repairing; however, they generally have inadequate adhesion to wet surfaces, improper mechanical strength, poor hemostasis, and cytotoxicity. To address these challenges, a robust wet tissue adhesive based on collagen and starch materials (CoSt) is designed in this study. CoSt hydrogels integrate the feature of drainage, molecular penetration and strengthen cross-linking similar to mussel, ivy, and oyster glues, which remove interfacial water quickly, reinforce tough dissipation and involve multiple reversible dynamic interactions. Therefore, they form strong adhesion and sutureless sealing of injured tissues, accompanying actuate robust biointerfaces in direct contact with tissue liquids or blood, resolving the crucial impediments with sutures and commercially accessible adhesives. The novel bioadhesive shows repeatable strong wet tissue adhesiveness (62 ± 4.8 KPa), high sealing performance (153.2 ± 35.1 mmHg), fast self-healing ability, excellent injectability, and shape adaptability. For different hemostatic needs in rat models of tail amputation, skin incision, severe liver, abdominal aorta, and transected nerve injuries, the CoSt hydrogel shows better hemostatic efficiency than fibrin glue because of the coordinate efficacy of tough wound sealing property, outstanding red blood cell arresting capability, and the activation of hemostatic barrier membrane. Moreover, in vivo investigation of the skin injury repair of the rat model validate that CoSt hydrogels accelerate wound healing and functional recovery via skin damage/defects. Tough wet adhesion, quick hemostasis, distinguished biocompatibility, suitability to match irregular-shaped target sites, and good wound healing promotion of the CoSt hydrogel makes it a prospective bioadhesive for various biomedical applications.     

High‐Performance Thiol–Ene Composites Unveil a New Era of Adhesives Suited for Bone Repair

The use of adhesives for fracture fixation can revolutionize the surgical procedures toward more personalized bone repairs. However, there are still no commercially available adhesive solutions mainly due to the lack of biocompatibility, poor adhesive strength, or inadequate fixation protocols. Here, a surgically realizable adhesive system capitalizing on visible light thiol–ene coupling chemistry is presented. The adhesives are carefully designed and formulated from a novel class of chemical constituents influenced by dental resin composites and self‐etch primers. Validation of the adhesive strength is conducted on wet bone substrates and accomplished via fiber‐reinforced adhesive patch (FRAP) methodology. The results unravel, for the first time, on the promise of a thiol–ene adhesive with an unprecedented shear bond strength of 9.0 MPa and that surpasses, by 55%, the commercially available acrylate dental adhesive system Clearfil SE Bond of 5.8 MPa. Preclinical validation of FRAPs on rat femur fracture models details good adhesion to the bone throughout the healing process, and are found biocompatible not giving rise to any inflammatory response. Remarkably, the FRAPs are found to withstand loads up to 70 N for 1000 cycles on porcine metacarpal fractures outperforming clinically used K‐wires and match metal plates and screw implants.     

Highly Customizable Bone Fracture Fixation through the Marriage of Composites and Screws

Open reduction internal fixation (ORIF) metal plates provide exceptional support for unstable bone fractures; however, they often result in debilitating soft-tissue adhesions and their rigid shape cannot be easily customized by surgeons. In this work, a surgically feasible ORIF methodology, called AdhFix, is developed by combining screws with polymer/hydroxyapatite composites, which are applied and shaped in situ before being rapidly cured on demand via high-energy visible-light-induced thiol–ene coupling chemistry. The method is developed on porcine metacarpals with transverse and multifragmented fractures, resulting in strong and stable fixations with a bending rigidity of 0.28 (0.03) N m² and a maximum load before break of 220 (15) N. Evaluations on human cadaver hands with proximal phalanx fractures show that AdhFix withstands the forces from finger flexing exercises, while short- and long-term in vivo rat femur fracture models show that AdhFix successfully supports bone healing without degradation, adverse effects, or soft-tissue adhesions. This procedure represents a radical new approach to fracture fixation, which grants surgeons unparalleled customizability and does not result in soft-tissue adhesions.     

Liquid Bandage Harvests Robust Adhesive,Hemostatic, and Antibacterial Performances as a First‐Aid Tissue Adhesive

Massive bleeding and wound infection after tissue trauma are the major dangerous factors of casualties in disasters; hence, first‐aid supplies that can greatly achieve wound closure and effectively control the hemorrhage and infection are urgently needed. Although existing tissue adhesives can adhere to the tissue surfaces and achieve rapid wound closure, most of them have limited hemostatic and antibacterial capacities, making them unsuitable as the first‐aid tissue adhesives. In this study, inspired by the inherent hemostatic and antibacterial capacities of chitosan and the excellent tissue integration capacity originating from a Schiff base reaction, liquid bandage (LBA), an in situ imine crosslinking‐based photoresponsive chitosan hydrogel (NB‐CMC/CMC hydrogel), is developed for emergency wound management. Upon UV irradiation, o‐nitrobenzene in modified carboxymethyl chitosan (CMC) converts to o‐nitrosobenzaldehyde that subsequently crosslinks with amino groups on tissue surface, which endows the LBA with superior tissue adhesive performance. LBA's hemostatic and antibacterial properties can be tuned by the mass ratio of NB‐CMC/CMC. Moreover, it exhibits satisfactory biocompatibility, biodegradability, and the capability to enhance wound healing process. This study sheds new light on the development of a multifunctional hydrogel‐based first‐aid tissue adhesive that can achieve robust tissue adhesion, effectively control bleeding, prevent bacterial infection, and promote wound healing.     

Sculpting Bio-Inspired Surface Textures: An Adhesive Janus Periosteum

Existing artificial periostea faces difficulty in supporting the entire bone repair cycle due to the absence of adhesion-centric design and effective cell manipulation, leading to poor inhibition of soft tissue infiltration and induction of osteogenesis and angiogenesis. Here, a Janus periosteum with interior surface adhesion and exterior anatomical patterns to mimic the structure and function of natural periosteum is presented. Photo-crosslinkable polymers are employed to replicate the exterior anisotropic surface structured microgrooves for cell fate manipulation and assemble gecko-inspired fibrillar setae arrays for interior surface adhesion. To further bolster its underwater adhesiveness, mussel-inspired poly (dopamine methacrylamide-co-hydroxyethyl methacrylate) (PDMH) is coated onto the periosteum surfaces. This periosteum presents adhesiveness with strong shear and normal adhesion in both dry and wet conditions due to the coordinated interactions of micro setae arrays and PDMH coating; it also boasts effective cell modulation for enhanced synchronous osteogenesis and angiogenesis, without the aid of growth factors. Moreover, the Janus periosteum is found to enhance bone regeneration in vivo with increased new bone formation and neovascularization. It is envisioned that this Janus periosteum will be able to streamline bone fracture surgical repair as a rapidly adhesive, low-maintenance yet robust bandage to significantly cut down the healing phase.     

Biomimetic Glycopolypeptide Hydrogels with Tunable Adhesion and Microporous Structure for Fast Hemostasis and Highly Efficient Wound Healing

Despite clinical applications of the first-generation tissue adhesives and hemostats, the correlation among microstructure and hemostasis of hydrogels with wound healing is less understood and it is elusive to design high-performance hydrogels to meet worldwide growing demands in wound closure, hemostasis, and healing. Inspired by the microstructure of extracellular matrix and mussel-mimetic chemistry, two kinds of coordinated and covalent glycopolypeptide hydrogels are fabricated, which present tunable tissue adhesion strength (14.6–83.9 kPa) and microporous structure (8–18 µm), and lower hemolysis <1.5%. Remarkably, the microporous size mainly controls the hemostasis, and those hydrogels with larger pores of 16–18 µm achieve the fastest hemostasis of ≈14 s and the lowest blood loss of ≈6% than fibrin glue and others. Moreover, both biocompatibility and hemostasis affect wound healing performance, as assessed by hemolysis, cytotoxicity, subcutaneous implantation, and hemostasis and healing assays. Importantly, the glycopolypeptide hydrogel-treated rat-skin defect model achieves full wound closure and regenerates thick dermis and epidermis with some hair follicles on day 14. Consequently, this work not only establishes a versatile method for constructing glycopolypeptide hydrogels with tunable adhesion and microporous structure, fast hemostasis, and superior healing functions, but also discloses a useful rationale for designing high-performance hemostatic and healing hydrogels.     

Switching On and Off Macrophages by a “Bridge-Burning” Coating Improves Bone-Implant Integration under Osteoporosis

Osteoporosis poses substantial challenges for biomaterials implantation. New approaches to improve bone-implant integration should resolve the fundamental dilemma of inflammation—proper inflammation is required at early stages but should be suppressed later for better healing, especially under osteoporosis. However, precisely switching on and off inflammation around implants in vivo remains unachieved. To address this challenge, a “bridge-burning” coating material that comprises a macrophage-activating glycan covalently crosslinked by a macrophage-eliminating bisphosphonate to titanium implant surface is designed. Upon implantation, the glycan instructs host macrophages to release pro-osteogenic cytokines (“switch-on”), promoting bone cell differentiation. Later, increasingly mature bone cells secrete alkaline phosphatase to cleave the glycan-bisphosphonate complexes from the implant, which in turn selectively kill the proinflammatory macrophages (“switch-off”) that have completed their contribution—hence in the manner of “burning bridges”—to promote healing. In vivo examination in an osteoporotic rat model demonstrates that this coating significantly enhances bone-implant integration (88.4% higher contact ratio) through modulating local inflammatory niches. In summary, a bioresponsive, endogenously triggered, smart coating material is developed to sequentially harness and abolish the power of inflammation to improve osseointegration under osteoporosis, which represents a new strategy for designing immunomodulatory biomaterials for tissue regeneration.     

Model-based integration of control and supervision for one kind of curing process

The optimization of the cure schedule for one kind of adhesive die-attach curing process in the electronics industry is very difficult to achieve due to the lack of tools for the online measurement of the extent of reaction adhesives during curing. In practice, the cure schedule is typically determined in a trial-and-error process, even though this is costly and may not guarantee the reliability of the adhesive die attach. A novel model-based integration of cure schedule optimization, supervision, and decoupling control is introduced to maintain both reliability and throughput. First, a novel hybrid spectral/neural method is used to model the curing process. The model developed can accurately estimate the temperature field inside the chamber. Then, an approximate decoupling linearization controller is developed to suppress the coupling effects from different heating sources for a better temperature tracking. Finally, the optimal cure time and temperature setpoints are accurately calculated from the characteristics of the cure oven and the cure kinetics of the adhesives used. The method is straightforward and effective, and can be easily applied to the curing supervision. Such a system-wide integration of control and supervision can be utilized to replace the traditionally used, unreliable trial-and-error process, and will provide an optimal production that is able to adapt to varying operating conditions.     

Injectable Biomimetic Hydrogel Guided Functional Bone Regeneration by Adapting Material Degradation to Tissue Healing

The treatment of irregular bone defects remains a clinical challenge since the current biomaterials (e.g., calcium phosphate bone cement (CPC)) mainly act as inert substitutes, which are incapable of transforming into a regenerated host bone (termed functional bone regeneration). Ideally, the implant degradation rate should adapt to that of bone regeneration, therefore providing sufficient physicochemical support and giving space for bone growth. This study aims to develop an injectable biomaterial with bone regeneration-adapted degradability, to reconstruct a biomimetic bone-like structure that can timely transform into new bone, facilitating functional bone regeneration. To achieve this goal, a hybrid (LP-CPC@gelatin, LC) hydrogel is synthesized via one-step incorporation of laponite (LP) and CPC into gelatin hydrogel, and the LC gel degradation rate is controlled by adjusting the LP/CPC ratio to match the bone regeneration rate. Such an LC hydrogel shows good osteoinduction, osteoconduction, and angiogenesis effects, with complete implant-to-new bone transformation capacity. This 2D nanoclay-based bionic hydrogel can induce ectopic bone regeneration and promote ligament graft osseointegration in vivo by inducing functional bone regeneration. Therefore, this study provides an advanced strategy for functional bone regeneration and an injectable biomimetic biomaterial for functional skeletal muscle repair in a minimally invasive therapy.     

镀Ni管壳侧壁硅橡胶粘接开裂机理研究

A型号硅橡胶粘接在镀Ni管壳侧壁后存在开裂情况，包括初始加工后胶点开裂、经历单次清洗后开裂，以及经历随机振动等可靠性试验后开裂，这会导致连接失效等一系列可靠性问题。文章针对A型号硅橡胶在镀Ni管壳侧壁引线加固时出现开裂的问题，进行了引线粘接极限破坏力理论计算、不同胶点直径和粘胶间距的仿真，以及等离子清洗提升表面能等研究。研究结果表明，优化引线粘接结构并对镀Ni管壳进行等离子体清洗可以明显提升A型号硅橡胶在镀Ni管壳侧壁粘接的可靠性。相关研究结果可以用于A型号硅橡胶实际生产。     

Cucurbit[n]uril Supramolecular Hydrogel Networks as Tough and Healable Adhesives

Supramolecular noncovalent interactions are widely found in natural adhesion phenomena to control macroscopic adhesion and accomplish a variety of complex functions. Such supramolecular adhesives could impart the interfaces with intriguing properties, e.g., energy dissipation and self‐healing, on account of their dynamic nature. Here, we demonstrate that cucurbit[8]uril (CB[8])‐based supramolecular hydrogel networks can function as dynamic adhesives for diverse nonporous (e.g., glass, stainless steel, aluminum, copper, and titanium) and porous substrates (wood and bone). Without any surface prefunctionalization or introduction of curing agents, these CB[8] hydrogel networks can be readily applied by curing around the softening temperature, forming a tough and healable adhesive interlayer. The ability to fabricate a robust sandwich model consisting of substrate–CB[8] hydrogel network–substrate enables a number of applications including stretchable and wearable electronics, hybrid systems for biomedical devices or tissue/bone regeneration.     

Double Cross-Linked Biomimetic Hyaluronic Acid-Based Hydrogels with Thermo-Stimulated Self-Contraction and Tissue Adhesiveness for Accelerating Post-Wound Closure and Wound Healing

When skin trauma occurs, rapid achievement of the post-wound closure is required to prevent microbial invasion, inhibit scar formation and promote wound healing. To develop a wound dressing for accelerating post-wound-closure and wound healing, a thermo-responsive and tissue-adhesive hydrogel with interpenetrating polymer networks (IPN) is fabricated based on N-dimethylbisacrylamide (NIPAM) and glutaraldehyde (GTA) cross-linked hyaluronic acid (HA). Results not only confirm the thermo-stimulated self-contraction and tissue adhesiveness of the HA-based IPN (PNI-HA), which effectively aids wound closure via mechanical stretch, but also verify the hemocompatibility and cytocompatibility of PNI-HA that tend to accelerate wound healing. In vivo, a mouse model of total skin defect demonstrates that PNI-HA acting as hydrogel sealant significantly achieves the sutureless post-wound-closure at the early stage of wound healing, and then promotes wound healing by reducing inflammatory cells infiltration, promoting angiogenesis as well as reducing collagen deposition. These results indicate that the developed thermo-responsive and tissue-adhesive hydrogel dressing offers a candidate to serve as a tissue sealant for wound healing.     

Piezo-Augmented and Photocatalytic Nanozyme Integrated Microneedles for Antibacterial and Anti-Inflammatory Combination Therapy

Wound infection is arguably the most common, and potentially the most devastating, complication of the wound healing process. The ideal treatment strategy has to eliminate bacteria, alleviate inflammation, and promote wound healing and skin formation. Herein, a multifunctional heterostructure is designed consisting of ultrasmall platinum–ruthenium nanoalloys and porous graphitic carbon nitride C₃N₅ nanosheets (denoted as PtRu/C₃N₅), which concurrently possesses piezoelectric enhanced oxidase -mimic nanozyme activity and photocatalytic hydrogen gas production capacity. Moreover, these hybrid nanotherapeutics are integrated in natural hyaluronic acid microneedles, which exhibit almost 100% broad-spectrum antibacterial efficacy against multiple bacterial strains in vitro and in vivo within 10 min ultrasound treatment, and effectively inhibit inflammation reactions after 1 h visible light irradiation, promising for accelerating the cutaneous wound healing in the bacterial infected mice. This study highlights a competitive strategy for development of all-in-one antibacterial and anti-inflammatory therapies.     

Material–Structure–Function Integrated Additive Manufacturing of Degradable Metallic Bone Implants for Load-Bearing Applications

The integration of bio-adaptable performance, elaborate structure, and biological functionality for degradable bone implants is crucial in harnessing the body's regenerative potential to remold load-bearing bone defects. Herein, material–structure–function integrated additive manufacturing (MSFI-AM) is deployed to innovate novel zinc-based bone implants, namely Zn–Mg–Cu alloy. In situ alloying of AM and boundary engineering strategy yield prominent mechanical properties, and the degradation products enable a mechanical self-strengthened effect, thus coordinating mechanical degeneration and promoting mechanical adaptability. In addition, MSFI-oriented Zn alloy implants successfully manifest in situ multifunctions of augmenting osteogenesis, immunoregulation, angiogenesis, and anti-infective activity in vitro and expediting bone ingrowth and regeneration in vivo through the sustained release of divalent metal cations and triply periodic minimal surface (TPMS) structure construction. Overall, MSFI-AMed Zn alloy implants signify promising clinical translation prospects for load-bearing applications, and an integrated approach is proposed to endow degradable bone implants with boosted bio-adaptable performance and in situ bio-multifunctions.     

Osteoconductive Performance of Carbon Nanotube Scaffolds Homogeneously Mineralized by Flow‐Through Electrodeposition

The treatment of bone lesions, including fractures, tumor resection and osteoporosis, is a common clinical practice where bone healing and repair are pursued. It is widely accepted that calcium phosphate‐based materials improve integration of biomaterials with surrounding bone tissue and further serve as a template for proper function of bone‐forming cells. Within this context, mineralization on preformed substrates appears as an interesting and successful alternative for mineral surface functionalization. However, mineralization of “true” 3D scaffolds –in which the magnitude of the third dimension is within the same scale as the other two– is by no means a trivial issue because of the difficulty to obtain a homogeneous mineral layer deposited on the entire internal surface of the scaffold. Herein, a “flow‐through” electrodeposition process is applied for mineralization of 3D scaffolds composed of multiwall carbon nanotubes and chitosan. It is demonstrated that, irrespective of the experimental conditions used for electrodeposition (e.g., time, temperature and voltages), the continuous feed of salts provided by the use of a flow‐through configuration is the main issue if one desires to coat the entire internal structure of 3D scaffolds with a homogeneous mineral layer. Finally, mineralized scaffolds not only showed a remarkable biocompatibility when tested with human osteoblast cells, but also enhanced osteoblast terminal differentiation (as early as 7 days in calcifying media).