Bone Adhesion Research Articles

Design and Improvement of Bone Adhesive in response to Clinical Needs.

Fracture represents one of the most common diagnoses in contemporary medical practice, with the majority of cases traditionally addressed through metallic device fixation. However, this approach is marred by several drawbacks, including prolonged operative durations, considerable expenses, suboptimal applicability to comminuted fractures, increased infection risks, and the inevitable requirement for secondary surgery. The inherent advantages of bone adhesives in these fields have garnered the attention of orthopedic surgeons, who have commenced utilizing biocompatible and biodegradable bone adhesives to bond and stabilize bone fragments. Regrettably, the current bone adhesives generally exhibit insufficient adhesive strength in vivo environments, and it is desirable for them to possess effective osteogenesis to facilitate fracture healing. Consequently, aligning bone adhesives with practical clinical demands remains a significant hurdle, which has catalyzed a surge in research endeavors. Within this review, the conceptual framework, characteristics, and design ideas of bone adhesives based on clinical needs are delineated. Recent advancements in this domain, specifically focusing on the enhancement of two pivotal characteristics-adhesive strength and osteogenic potential are also reviewed. Finally, a prospective analysis of the future advancements in bone adhesives, offering new insights into solutions for diverse clinical problems is presented.

Injectable double-crosslinked bone cement with enhanced bone adhesion and improved osteoporotic pathophysiological microenvironment for osteoregeneration in osteoporosis

The osteoporotic bone defect caused by excessive activity of osteoclasts has posed a challenge for public healthcare. However, most existing bioinert bone cement fails to effectively regulate the pathological bone microenvironment and reconstruct bone homeostasis in the presence of osteoclast overactivity and osteoblast suppression. Herein, inspired by natural bone tissue, an in-situ modulation system for osteoporotic bone regeneration is developed by fabricating an injectable double-crosslinked PEGylated poly(glycerol sebacate) (PEGS)/calcium phosphate cement (CPC) loaded with sodium alendronate (ALN) (PEGS/CPC@ALN) adhesive bone cement. By incorporating ALN, the organic-inorganic interconnection within PEGS/CPC@ALN results in a 100 % increase in compression modulus and energy dissipation efficiency. Additionally, PEGS/CPC@ALN effectively adheres to the bone by bonding with amine and calcium ions present on the bone surface. Moreover, this in-situ regulation system comprehensively mitigates excessive bone resorption through the buffering effect of CPC to improve the acidic microenvironment of osteoporotic bone and the release of ALN to inhibit hyperactive osteoclasts, and facilitates stem cell proliferation and differentiation into osteoblasts through calcium ion release. Overall, the PEGS/CPC@ALN effectively regulates the pathological microenvironment of osteoporosis while promoting bone regeneration through synergistic effects of drugs and materials, thereby improving bone homeostasis and enabling minimally invasive treatment for osteoporotic defects.

Mg2+ - Ca2+ chelating citric acid crosslinked gelatin, a bone adhesive composed of hydroxyapatite and calcined dolomite: Physicochemical characteristics and in-vitro biological activity

Hydroxyapatite-based bone adhesives have strong bond strength and good adsorbability, however, they also have some disadvantages such as poor mechanical strength, fast curing reaction rate and high exothermic strength, which limit their wide application in bone tissue engineering. In this study, hydroxyapatite-based bone adhesive was prepared by solid-liquid blended crosslinking followed by heating. The prepared bone adhesive has two components: (i) is a mineral composed of calcined dolomite and montmorillonite and (ii) is organic composite composed of citric acid and gelatine. The optimum solid-liquid ratio (0.50 g/mL) of the bone adhesive was determined based on the bond strength of nano-hydroxyapatite/calcined dolomite/citric acid/gelatin system. The best physicochemical properties of the bond adhesive were obtained when the composition of the bone adhesive was as follows: 20 wt% citric acid, 17 wt% gelatin and 12 wt% calcined dolomite. The acquired curing time of bone adhesive was 10.5 min, comparable to the necessity for surgery (5–30 min); moreover, the adhesive strength and compressive strength of the bone adhesive were 12.18 MPa and 9.36 MPa respectively, obtained after being placed in the air for 168 h; besides, the porosity (16.8 %) was found quite suitable. Upon this, a certain amount of montmorillonite was added with calcined dolomite to prepare bone adhesive, resulting reduction in the adhesive strength (10.19 MPa) and compressive strength (7.109 MPa), but improved the biocompatibility of the system. The absorbency of the hydroxyapatite-based bone adhesives in deionized water and Tris-HCl buffer solution was found to be 27.19 % and 18.68 %, respectively, ascertaining that such bone adhesives are efficient in absorbing certain blood and tissue fluid in the biological body and promoting the absorption of required nutrients in the process of bone repair. In addition, the formation of osteoid apatite in the In-vitro study, proved by FTIR and EDAX analysis, rationalized for improving the osteogenic activity. Furthermore, after 56 days of immersion in the Tris-HCl buffer solution, the weight loss rate of the bone adhesive reached up to 42.73 %, indicating that the bone adhesive had satisfactory degradation performance. Finally, in the cytotoxicity test, the survival rate of mouse precranial bone cells was found to be greater than 80 % after adding the prepared bone adhesive, demonstrating its sufficient biocompatibility.

A bioinspired polymer composite with tough, fatigue-resistant adhesion, and high interfacial thermal conductance via interfacial crosslinking

Achieving tough, fatigue-resistant adhesion and high interfacial thermal conductance (ITC) is crucial in various applications such as electronic packaging, soft electronics, and batteries, yet challenging. Herein, inspired by the tendon to bone adhesion, we present a polymer composite fabricated by incorporating interfacial crosslinking of boronic ester into commercially available polybutadiene that bind with fillers and various substrates. We demonstrate that fillers and interfacial crosslinking can enhance adhesion and ITC while also hindering crack propagation, resulting in enhanced fatigue resistance adhesion. Therefore, the fabricated composite exhibits excellent adhesion strength (12.07 MPa), ultra-tough adhesion (5885.85 J m−2), adhesion fatigue threshold (1377.23 J m−2), together with high ITC (118.4 MW m−2 K−1). We also demonstrate that the linear correlation between ITC and the adhesion fatigue threshold surpasses the relationship with adhesion strength and adhesion energy. In addition, the prepared polymer composite shows effective heat dissipation for electronic devices in various working conditions. It is anticipated that our research will stimulate the conceptualization and utilization of a diverse array of composite materials, including high-performance adhesives and polymer composites with high thermal conductivity.

A novel surgical diamond spherical wheel to prevent bone adhesion with superhydrophobic and super-slippery coatings

Ordinary commercial diamond spherical wheels are extensively used in bone grinding surgeries. However, a persistent issue arises from bone debris adhering to the wheel surface, leading to elevated temperatures during the bone grinding process. To address this, the study developed a novel spherical wheel with a superhydrophobic and super-slippery coating to prevent the bone debris adhesion. Initially, a superhydrophobic and super-slippery coating was successfully designed and fabricated with mixture of ODA-GO, PDMS, KH-550, and epoxy resin E44. The coating's surface morphology, chemical composition, and durability were comprehensively characterized. Subsequently, the coating was applied to diamond spherical grinding wheels for bone grinding experiments. The results demonstrate that a coating with exposed ODA-GO forms a rough structure with optimal component parameters, achieving a contact angle of 158° and a sliding angle of 4.2°. Furthermore, the superhydrophobic and super-slippery coating exhibits exceptional wear and slipperiness resistance even after 100 cycles, maintaining a contact angle of 135° and a sliding angle of 8.5°. The use of this novel spherical wheel significantly mitigates bone debris adhesion. This study not only provides valuable insights into the mechanisms of anti-adhesion but also introduces a promising technique for enhancing the performance of diamond spherical wheels.

Implant surface modifications and their impact on osseointegration and peri-implant diseases through epigenetic changes: A scoping review.

Dental implant surfaces and their unique properties can interact with the surrounding oral tissues through epigenetic cues. The present scoping review provides current perspectives on surface modifications of dental implants, their impact on the osseointegration process, and the interaction between implant surface properties and epigenetics, also in peri-implant diseases. Findings of this review demonstrate the impact of innovative surface treatments on the epigenetic mechanisms of cells, showing promising results in the early stages of osseointegration. Dental implant surfaces with properties of hydrophilicity, nanotexturization, multifunctional coatings, and incorporated drug-release systems have demonstrated favorable outcomes for early bone adhesion, increased antibacterial features, and improved osseointegration. The interaction between modified surface morphologies, different chemical surface energies, and/or release of molecules within the oral tissues has been shown to influence epigenetic mechanisms of the surrounding tissues caused by a physical-chemical interaction. Epigenetic changes around dental implants in the state of health and disease are different. In conclusion, emerging approaches in surface modifications for dental implants functionalized with epigenetics have great potential with a significant impact on modulating bone healing during osseointegration.

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.

СРАВНИТЕЛЬНАЯ ХАРАКТЕРИСТИКА МЕТОДОВ ИММОБИЛИЗАЦИИ ОТЛОМКОВ ПРИ ПЕРЕЛОМАХ НИЖНЕЙ ЧЕЛЮСТИ

Item. A review of the literature is presented on the current problem of maxillofacial surgery – methods of fixation of bone fragments in fractures of the lower jaw. The purpose of the study is to study publications on methods of fixation of fragments in fractures of the lower jaw in the comparative aspect of their influence on the clinical course. Methodology. The publications of domestic and foreign authors on modern methods of fixation of bone fragments in fractures of the lower jaw were studied, and a comparative analysis of their effectiveness was carried out. Results. Currently, orthopedic and surgical methods of immobilization of bone fragments are used, which are used both in isolation and in various combinations. During surgical treatment with the help of mini-plates, it is possible to perform optimal reposition and stable fixation of fragments, however, the traumatic nature of the operation, leading to bone hypoxia, slows down the processes of reparative osteogenesis and leads to the development of postoperative complications. The use of bone glue-cement makes it possible to achieve reliable fixation of bone fragments, accelerate the formation of a callus. At the same time, there is no need to remove the glue, since it is a biodegradable material. Conclusions 1. None of the currently used methods of fixation of bone fragments in clinical practice for fractures of the mandible, both orthopedic and surgical, as well as in their combination, can fully meet the optimal conditions of reparative osteogenesis. 2. A promising alternative method is the use of bone adhesives that fill the bone voids between fragments, which contributes to their stable fixation and reparative osteogenesis, biodegrading simultaneously with the formation of a callus.

Novel polyurethane foam with low released heat for application in bone binder

AbstractBecause of the significant advantages of bone adhesives compared with traditional mechanical fixation, many scholars have studied polyurethane bone adhesives. However, polyurethane will release a lot of heat in the reaction process, producing high temperature. The high temperature does not only easily cause a human discomfort but also will destroy the tissue structure of human. In this paper, a new polyurethane composite based on phase transition materials and hydroxyapatite is prepared to reduce released heat for application in bone binder. The mechanical properties, adhesive strength, and released heat‐induced temperature of polyurethane composite are investigated in detail. It exhibits good viscoelastic performance with a large elastic deformation (>30%) and good adhesive strength (>0.2 MPa). Furthermore, the released heat of polyurethane composite is effectively reduced, in which the temperature drastically decreases from 110.4 to 41.8°C. The work does not only confirm formation of high‐performance bone binder but also provides a new method to reduce released heat of polyurethane for various applications.

Degradable Nanohydroxyapatite-Reinforced Superglue for Rapid Bone Fixation and Promoted Osteogenesis.

Bone glue with robust adhesion is crucial for treating complicated bone fractures, but it remains a formidable challenge to develop a "true" bone glue with high adhesion strength, degradability, bioactivity, and satisfactory operation time in clinical scenarios. Herein, inspired by the hydroxyapatite and collagen matrix composition of natural bone, we constructed a nanohydroxyapatite (nHAP) reinforced osteogenic backbone-degradable superglue (O-BDSG) by in situ radical ring-opening polymerization. nHAP significantly enhances adhesive cohesion by synergistically acting as noncovalent connectors between polymer chains and increasing the molecular weight of the polymer matrix. Moreover, nHAP endows the glue with bioactivity to promote osteogenesis. The as-prepared glue presented a 9.79 MPa flexural adhesion strength for bone, 4.7 times that without nHAP, and significantly surpassed commercial cyanoacrylate (0.64 MPa). O-BDSG exhibited degradability with 51% mass loss after 6 months of implantation. In vivo critical defect and tibia fracture models demonstrated the promoted osteogenesis of the O-BDSG, with a regenerated bone volume of 75% and mechanical function restoration to 94% of the native tibia after 8 weeks. The glue can be flexibly adapted to clinical scenarios with a curing time window of about 3 min. This work shows promising prospects for clinical application in orthopedic surgery and may inspire the design and development of bone adhesives.

First-in-Human Pilot Study to Assess Methodology for Using a Mineral-Organic Bone Adhesive for Optimization of Primary Stability and Implant Success for Implants Glued into Immediate Extraction Sockets and Immediately Temporized: Pilot Study.

To assess the handling properties and clinical function of a new class of material, a so-called mineral-organic bone adhesive (Tetranite; TN), which as yet has no precedent in orthopedic or oral and maxillofacial surgery, for clinically unstable implants placed in immediate extraction sockets and immediately temporized in the anterior maxilla. A cohort of up to 15 patients requiring between one and four immediate dental implants placed into maxillary extraction sockets from canine to canine were eligible for inclusion. Implants had to be unstable with an insertion torque of < 15 Ncm. Implants were then stabilized using TN, which was allowed to set before reassessing stability using both torque and resonance frequency measurements. Implant stability quotients (ISQs) taken after TN setting were compared to ISQs taken prior to its application, and the implants had to demonstrate resistance to a forward torque of 20 Ncm to be considered stable. ISQs were monitored at 1 week and 1, 3, 7, and 12 months postplacement. In addition, peri-implant tissue health was monitored, adverse events were recorded, and implant success was determined at 1 year postplacement. Eleven patients received a total of 14 implants. Three out of the first six implants failed within 1 month (50%), and thus a protocol amendment was made to remove steps considered potentially destructive to the bonding process. As a result of these amendments, only one further failure was experienced for the next eight implants placed (12.5%). Mean ISQ data averaged for buccolingual and mesiodistal measurements demonstrated a baseline value before TN application of 59.1 Ncm (SD: ± 9.7; range: 40.5 to 73.0). After final setting of the TN, mean ISQ measured 71.9 Ncm (± 6.5; 56.0 to 80.0). At 3 months, just prior to restoration placement, mean ISQ measured 71.0 Ncm (± 6.6; 57.0 to 78.0). Thereafter, the mean ISQ continued to increase at both the 7- and 12-month follow-ups with scores of 78.9 (± 4.6; 72.0 to 84.5) and 80.3 (± 3.8; 74.5 to 85.0), respectively. The surviving 10 implants went on to be fully restored and remained in function beyond the end of the study period to yield a final success rate of 71.4%. The purpose of a first-in-human study is to demonstrate an extrapolation of preclinical data into the controlled human clinical arena. It is an opportunity to learn what does and does not translate well from experimental data. In that regard, the current pilot study can be deemed a complete success. The implant survival rate of 71.4%, while disappointing, should be considered in light of the protocol amendments identified, the user handling experience learned, and the opportunity to modify the material to better perform in the human patient, as all represent important lessons learned. The notable increase in ISQ sheds light on the nature by which the glue was substituted for bone to yield a stable implant by the end of the study period.

A NOVEL BIOMIMETIC BONE ADHESIVE: TRANSLATION FROM SMALL TO LARGE ANIMAL PRECLINICAL MODEL ON THE PATH TO FIRST IN-HUMAN USE

Surgeons treating fractures with many small osteochondral fragments have often expressed the clinical need for an adhesive to join such fragments, as an adjunct to standard implants. If an adhesive would maintain alignment of the articular surfaces and subsequently heal it could result in improved clinical outcomes. However, there are no bone adhesives available for clinical indications and few pre-clinical models to assess safety and efficacy of adhesive biomaterial candidates. A bone adhesive candidate based on water, α-TCP and an amino acid phosphoserine was evaluated in-vivo in a novel murine bone core model (preliminary results presented EORS 2019) in which excised bone cores were glued back in place and harvested @ 0, 3, 7, 14, 28 and 42days. Adhesive pull-out strength was demonstrated 0–28 days, with a dip at 14 days increasing to 11.3N maximum. Histology 0–42 days showed the adhesive progressively remodelling to bone in both cancellous and cortical compartments with no signs of either undesirable inflammation or peripheral ectopic bone formation. These favourable results suggested translation to a large animal model.A porcine dental extraction socket model was subsequently developed where dental implants were affixed only with the adhesive. Biomechanical data was collected @ 1, 14, 28 and 56 days, and histology at 1,14,28 and 56 days. Adhesive strength assessed by implant pull-out force increased out to 28 days and maintained out to 56 days (282N maximum) with failure only occurring at the adhesive bone interface. Histology confirmed the adhesive's biocompatibility and osteoconductive behavior. Additionally, remodelling was demonstrated at the adhesive-bone interface with resorption by osteoclast-like cells and followed by new bone apposition and substitution by bone. Whilst the in-vivo dental implant data is encouraging, a large animal preclinical model is needed (under development) to confirm the adhesive is capable of healing, for example, loaded osteochondral bone fragments.Acknowledgements: The murine study was supported, in part, by the Swedish Foundation for Strategic Research (#RMA15-0110).

Polyacrylic acid-reinforced organic-inorganic composite bone adhesives with enhanced mechanical properties and controlled degradability.

Bone adhesives, as alternatives to traditional bone fracture treatment methods, have great benefits in achieving effective fixation and healing of fractured bones. However, current available bone adhesives have limitations in terms of weak mechanical properties, low adhesion strength, and inappropriate degradability, hindering their clinical applications. The development of bone adhesives with strong mechanical properties, adhesion strength, and appropriate degradability remains a great challenge. In this study, polyacrylic acid was incorporated with tetracalcium phosphate and O-phospho-L-serine to form a new bone adhesive via coordination and ionic interactions to achieve exceptional mechanical properties, adhesion strength, and degradability. The bone adhesive could achieve an initial adhesion strength of approximately 3.26 MPa and 0.86 MPa on titanium alloys and bones after 15 min of curing, respectively, and it increased to 5.59 MPa and 2.73 MPa, after 24 h of incubation in water or simulated body fluid (SBF). The compressive strength of the adhesive increased from 10.06 MPa to 72.64 MPa over two weeks, which provided sufficient support for the fractured bone. Importantly, the adhesive started to degrade after 6 to 8 weeks of incubation in SBF, which is beneficial to cell ingrowth and the bone healing process. In addition, the bone adhesives exhibited favorable mineralization capability, biocompatibility, and osteogenic activity. In vivo experiments showed that it has a better bone-healing effect compared with the traditional polymethyl methacrylate bone cement. These results demonstrate that the bone adhesive has great potential in the treatment of bone fractures.

Development and Analysis of Biomaterial Based on Calcium Sulfate Hemihydrate and Epoxy Resin

Bone deformation and the degradation of the joint are one of the most common problems faced around the world, especially after the age of 50. Materials like Allograft and Polymethyl-Methacrylate (PMMA) are used in traditional orthotics and prosthetics, and for bone grafting/filling procedures, however, these materials can be expensive. This research proposes, the fabrication of a novel material by utilizing Calcium-Sulfate Hemihydrate (CaSO4. 1/2H2O), and epoxy resin, which can be used as a cost-effective orthotic and prosthetic material. The materials are already used as bone adhesives and bone grafts, hence, are compatible and non-toxic. The fabricated composite material possesses physical properties closest to the natural human bone and is also hydrophilic. Samples with different ratios of the constituents were fabricated and tested for their hardness, compression, and contact angle values using a Hardness tester, PASCO compression tester, and Image J software. The hardness test results indicate that sample 1 has the hardness value i.e., 29.5 ± 2.50 HV in contrast the hardness value of a human bone is found to be 33.3

Ternary thiol-ene systems as high-performance bone adhesives for potential clinical use

Ternary thiol-ene systems as high-performance bone adhesives for potential clinical use

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.

Overcoming the Dilemma of In Vivo Stable Adhesion and Sustained Degradation by the Molecular Design of Polyurethane Adhesives for Bone Fracture Repair.

Bone adhesive is a promising candidate to revolutionize the clinical treatment of bone repairs. However, several drawbacks have limited its further clinical application, such as unreliable wet adhesive performance leading to fixation failure and poor biodegradability inhibiting bone tissue growth. By incorporating catechol groups and disulfide bonds into polyurethane (PU) molecules, an injectable and porous PU adhesive is developed with both superior wet adhesion and biodegradability to facilitate the reduction and fixation of comminuted fractures and the subsequent regeneration of bone tissue. The bone adhesive can be cured within a reasonable time acceptable to a surgeon, and then the wet bone adhesive strength is near 1.30MPa in 1h. Finally, the wet adhesive strength to the cortical bone will achieve about 1.70MPa, which is also five times more than nonresorbable poly(methyl methacrylate) bone cement. Besides, the cell culture experiments also indicate that the adhesives show excellent biocompatibility and osteogenic ability in vitro. Especially, it can degrade in vivo gradually and promote fracture healing in the rabbit iliac fracture model. These results demonstrate that this ingenious bone adhesive exhibits great potential in the treatment of comminuted fractures, providing fresh insights into the development of clinically applicable bone adhesives.

High-Throughput Screening of Thiol-ene Click Chemistries for Bone Adhesive Polymers.

Metal surgical pins and screws are employed in millions of orthopedic surgical procedures every year worldwide, but their usability is limited in the case of complex, comminuted fractures or in surgeries on smaller bones. Therefore, replacing such implants with a bone adhesive material has long been considered an attractive option. However, synthesizing a biocompatible bone adhesive with a high bond strength that is simple to apply presents many challenges. To rapidly identify candidate polymers for a biocompatible bone adhesive, we employed a high-throughput screening strategy to assess human mesenchymal stromal cell (hMSC) adhesion toward a library of polymers synthesized via thiol-ene click chemistry. We chose thiol-ene click chemistry because multifunctional monomers can be rapidly cured via ultraviolet (UV) light while minimizing residual monomer, and it provides a scalable manufacturing process for candidate polymers identified from a high-throughput screen. This screening methodology identified a copolymer (1-S2-FT01) composed of the monomers 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione (TATATO) and pentaerythritol tetrakis (3-mercaptopropionate) (PETMP), which supported highest hMSC adhesion across a library of 90 polymers. The identified copolymer (1-S2-FT01) exhibited favorable compressive and tensile properties compared to existing commercial bone adhesives and adhered to bone with adhesion strengths similar to commercially available bone glues such as Histoacryl. Furthermore, this cytocompatible polymer supported osteogenic differentiation of hMSCs and could adhere 3D porous polymer scaffolds to the bone tissue, making this polymer an ideal candidate as an alternative bone adhesive with broad utility in orthopedic surgery.

Bone-Adhesive Hydrogel for Effective Inhibition of M. tuberculosis and Osteoblast Regeneration.

Currently, bone tuberculosis (TB) treatment largely involves lifelong drug prescriptions and surgical intervention, resulting in poor quality of life for patients. Therefore, the fabrication of injectable scaffolds to form a solid framework around the defective bone region is gaining importance over the extensive use of antimicrobial inhibitors. Herein, we synthesized a novel bone-adhesive and thermoresponsive hydrogel via conjugation of poly(N-isopropylacrylamide-co-glycidyl methacrylate) (PNIPAM-co-GMA) and cysteine (CYS). Thiolation of the polymer enables chemical cross-linking with the bone glycoprotein, enhancing bone adhesion and permitting control of scaffold retention time. The PNIPAM-co-GMA-CYS hydrogel shows higher cross-linking behavior at 37 °C, forms a strong gel in 260 s, and has 151 kPa adhesion strength on cortical bone. The lead compounds 5-methyl-5H-[1,2,4]triazino[5,6-b]indole-3-thiol (MTIT) and N-tert-butyl-4-methyl-6-(5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-ylthio)pyrimidin-2-amine (TMTIPA) were identified by a high-throughput screening method. Effective MTIT and TMTIPA are encapsulated in bone-adhesive hydrogel separately, and both have a high release rate above >70% in 180 h. The MTIT- and TMTIPA-loaded PNIPAM-co-GMA-CYS showed an excellent bactericidal effect, reducing the relative intracellular bacterial survival in macrophages. Furthermore, the as-synthesized hydrogel has outstanding mechanical and biocompatibility properties to become a bone-replacing material and provide support to promote bone repair. This work presents a novel bone-adhesive PNIPAM-co-GMA-CYS for the sustained release of lead compounds toward promising alternative bone TB treatment.

A Novel Screwless Modification of the Khoury Plate Technique using an Innovative Bone Adhesive Formulated from Underwater Biomimetic Marine Proteins.

The Khoury plate technique has been widely utilized with much success over the past 2 decades to facilitate bone augmentations in critically deficient bone areas. Simply, the technique encompasses harvesting autogenous bone plates and utilizing them with external screw fixation. The rigidity of the bone plates enclosing the bony defect on both the buccal and lingual surfaces allows for tension free bone remodeling to occur favoring an ideal bone forming environment. Following, a 4-6 month healing period, a flap is raised, screws may be removed and implant placement then follows. With advancements made in tissue engineering, recently a novel mineral-organic resorbable bone adhesive (MORBA) formulated from underwater biomimetic marine proteins has been utilized for immediate fixation of either bone-to-bone or bone-to-metal. MORBA is a synthetic, injectable, self-setting, and resorbable load-bearing adhesive biomaterial that exhibits over 300 pounds of fixation strength. The unique adhesive properties of MORBA enable it to provide immediate stabilization of dental implants into host bone. The present article describes a novel modification of the Khoury plate technique by utilizing MORBA as a substitute for screws during the fixation of bone plates. A step by step protocol is described where this novel biomaterial was utilized as a substitute to screws favoring a more biological approach to this conventional technique. This novel modification is both surgically easier to conduct, and favors a more biocompatible option that avoids screw fixation and removal.