Antibacterial and Osteogenic Doxycycline Imprinted Bioglass Microspheres to Combat Bone Infection.

Currently, postoperative infection is a significant challenge in bone and dental surgical procedures, demanding the exploration of innovative approaches due to the prevalence of antibiotic-resistant bacteria. This study aims to develop a strategy for controlled and smart antibiotic release while accelerating osteogenesis to expedite bone healing. In this regard, temperature-responsive doxycycline (DOX) imprinted bioglass microspheres (BGMs) were synthesized. Following the formation of chitosan-modified BGMs, poly N-isopropylacrylamide (pNIPAm) was used for surface imprinting of DOX. The temperature-responsive molecularly imprinted polymers (MIPs) exhibited pH and temperature dual-responsive adsorption and controlled-release properties for DOX. The temperature-responsive MIP was optimized by investigating the molar ratio of N,N'-methylene bis(acrylamide) (MBA, the cross-linker) to NIPAm. Our results demonstrated that the MIPs showed superior adsorption capacity (96.85 mg/g at 35 °C, pH = 7) than nonimprinted polymers (NIPs) and manifested a favorable selectivity toward DOX. The adsorption behavior of DOX on the MIPs fit well with the Langmuir model and the pseudo-second-order kinetic model. Drug release studies demonstrated a controlled release of DOX due to imprinted cavities, which were fitted with the Korsmeyer-Peppas kinetic model. DOX-imprinted BGMs also revealed comparable antibacterial effects against Staphylococcus aureus and Escherichia coli to the DOX (control). In addition, MIPs promoted viability and osteogenic differentiation of MG63 osteoblast-like cells. Overall, the findings demonstrate the significant potential of DOX-imprinted BGMs for use in bone defects. Nonetheless, further in vitro investigations and subsequent in vivo experiments are warranted to advance this research.

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 ± 38 kPa 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.

Lignin derivatives-based hydrogels for biomedical applications.

Recently, numerous studies have been conducted on renewable polymers derived from different natural sources, exploring their suitability for diverse biomedical applications. Lignin as one of the main components of lignocellulosic has garnered significant attention as a promising alternative to petroleum-based polymers. This interest is primarily due to its cost-effectiveness, biocompatibility, eco-friendly nature, as well as its antioxidant and antimicrobial properties. These characteristics could be more beneficial when incorporating lignin into the formulation of value-added products. Although lignin has a chemical structure that is suitable for various applications, these characteristics require modifications to guarantee that the resultant materials display the desired biological, chemical, and physical properties when applied in the creation of biodegradable hydrogels, particularly for biomedical purposes. This study delineates the recent modification approaches that have been employed in the creation of lignin-based hydrogels. These strategies encompass both chemical and physical interactions with other polymers. Additionally, this review encompasses an examination of the current applications of lignin hydrogels, spanning their use as scaffolds for tissue engineering, carriers for pharmaceuticals, materials for wound dressings and biosensors, and elements in flexible and wearable electronics. Finally, we delve into the challenges and constraints associated with these materials, discuss the necessary steps required to attain the appropriate properties for the development of innovative lignin-based hydrogels, and derive conclusions based on the presented findings.

Co-release of nitric oxide and L-arginine from poly (ß-amino ester)-based adhesive reprogram macrophages for accelerated wound healing and angiogenesis in vitro and in vivo.

Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (ß-amino ester) (PßAE). In this regard, PßAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PßAE could provide suitable adhesive strength (~25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4-1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PßAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis (~ 3-4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (~1.5-2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (~98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PßAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.

Morphology-Dependent Immunomodulatory Coating of Hydroxyapatite/PEO for Magnesium-Based Bone Implants.

One of the most critical issues concerning orthopedic implants is the risk of chronic inflammation, which poses a threat to the bone healing process. Osteo-immunomodulation plays a pivotal role in implant technology by influencing proinflammatory and anti-inflammatory responses, ultimately promoting bone healing. This study aims to investigate the morphology-dependent osteo-immunomodulatory properties of a hydroxyapatite (HA)/plasma electrolytic oxidation (PEO)-coated WE43 alloy. In this context, following the PEO process with various operational parameters (duty cycles of 50-40, 50-20, 70-40%, and frequencies of 0.5, 0.8, and 1 kHz), a layer of HA was applied as the top coating using a straightforward hot-dip process. The results revealed the formation of the PEO layer with distinct morphologies and pore sizes, depending on the operational parameters. Specifically, a uniform PEO coating with small pore sizes (5.2-5.3 µm) led to the creation of plate-like HA particles, while a random-like HA structure formed on nonuniform surfaces with large pores (7.0-11.1 µm) of PEO. Moreover, it was observed that the plate-like HA coating exhibited higher adhesion strength than the random one (classified as class 2 vs class 3 based on cross-cut standards). Furthermore, electrochemical impedance spectroscopy (EIS) and polarization studies confirmed a substantial increase in the polarization resistance (680 kΩ) and total impedance (48 559.6 Ω) for the plate-like HA/PEO as compared to the substrate (an increase of 1511-fold and 311-fold, respectively) and the random HA/PEO samples (an increase of 85-fold and 18-fold, respectively). In addition, compared to random HA coatings, there was a significant enhancement in the viability (150% control vs 96% control), proliferation, and differentiation of MG63 cells when exposed to plate-like HA coatings. Moreover, surface morphology and chemistry pronouncedly impacted macrophages' viability, morphology, and phenotype. Notably, plate-like HA coatings resulted in a higher upregulation of BMP-2 and TGF-ß than proinflammatory cytokines (IL-6 and M-CSF), indicating a polarization of macrophage type 1 (M1) toward type 2 (M2). In summary, the bilayer HA/PEO coating exhibited remarkable osteo-immunomodulatory activity, making it highly appealing for use in bone implant applications.

Colorimetric pH-responsive and hemostatic hydrogel-based bioadhesives containing functionalized silver nanoparticles.

Here we develop and characterize a dual-cross-linked pH-responsive hydrogel based on the carboxyethyl chitosan-oxidized sodium alginate (CAO) containing silver nanoparticles (Ag NPs) functionalized with tannic acid/red cabbage (ATR). This hybrid hydrogel is formed via covalent and non-covalent cross-linking. The adhesive strength measured in contact with cow skin and compression strength is measured more than 3 times higher than that of CAO. Importantly, the incorporation of 1 â€‹wt% ATR into CAO significantly enhances the compression strength of CAO from 35.1 â€‹± â€‹2.1 â€‹kPa to 97.5 â€‹± â€‹2.9 â€‹kPa. Moreover, the cyclic compression tests confirm significantly higher elastic behavior of CAO after the addition of ATR-functionalized NPs to CAO. The CAO/ATR hydrogel is pH-sensitive and indicated remarkable color changes in different buffer solutions. The CAO/ATR also shows improved hemostatic properties and reduced clotting time compared to the clotting time of blood in contact with CAO hydrogel. In addition, while CAO/ATR is effective in inhibiting the growth of both Gram-positive and Gram-negative bacteria, CAO is only effective in inhibiting the growth of Gram-positive bacteria. Finally, the CAO/ATR hydrogel is cytocompatible with L929 fibroblasts. In summary, the resulting CAO/ATR hydrogel shows promising results in designing and constructing smart wound bioadhesives with high cytocompatibility, antibacterial properties, blood coagulation ability, and fast self-healing properties.

Antibacterial and pH-sensitive methacrylate poly-L-Arginine/poly (ß-amino ester) polymer for soft tissue engineering.

During the last decade, pH-sensitive biomaterials containing antibacterial agents have grown exponentially in soft tissue engineering. The aim of this study is to synthesize a biodegradable pH sensitive and antibacterial hydrogel with adjustable mechanical and physical properties for soft tissue engineering. This biodegradable copolymer hydrogel was made of Poly-L-Arginine methacrylate (Poly-L-ArgMA) and different poly (ß- amino ester) (PßAE) polymers. PßAE was prepared with four different diacrylate/diamine monomers including; 1.1:1 (PßAE1), 1.5:1 (PßAE1.5), 2:1 (PßAE2), and 3:1 (PßAE3), which was UV cross-linked using dimethoxy phenyl-acetophenone agent. These PßAE were then used for preparation of Poly-L-ArgMA/PßAE polymers and revealed a tunable swelling ratio, depending on the pH conditions. Noticeably, the swelling ratio increased by 1.5 times when the pH decreased from 7.4 to 5.6 in the Poly-L-ArgMA/PßAE1.5 sample. Also, the controllable degradation rate and different mechanical properties were obtained, depending on the PßAE monomer ratio. Noticeably, the tensile strength of the PßAE hydrogel increased from 0.10 ± 0.04 MPa to 2.42 ± 0.3 MPa, when the acrylate/diamine monomer molar ratio increased from 1.1:1 to 3:1. In addition, Poly-L-ArgMA/PßAE samples significantly improved L929 cell viability, attachment and proliferation. Poly-L-ArgMA also enhanced the antibacterial activities of PßAE against both Escherichia coli (~5.1 times) and Staphylococcus aureus (~2.7 times). In summary, the antibacterial and pH-sensitive Poly-L-ArgMA/PßAE1.5 with suitable mechanical, degradation and biological properties could be an appropriate candidate for soft tissue engineering, specifically wound healing applications.

Mussel-inspired lignin decorated cellulose nanocomposite tough organohydrogel sensor with conductive, transparent, strain-sensitive and durable properties.

A novel gel-based wearable sensor with environment resistance (anti-freezing and anti-drying), excellent strength, high sensitivity and self-adhesion was prepared by introducing biomass materials including both lignin and cellulose. The introduction of lignin decorated CNC (L-CNC) to the polymer network acted as nano-fillers to improve the gel's mechanical with high tensile strength (72 KPa at 25 °C, 77 KPa at -20 °C), excellent stretchability (803 % at 25 °C, 722 % at -20 °C). The abundant catechol groups formed in the process of dynamic redox reaction between lignin and ammonium persulfate endowed the gel with robust tissue adhesiveness. Impressively, the gel exhibited outstanding environment resistance, which could be stored for a long time (>60 days) in an open-air environment with a wide work temperature range (-36.5 °C-25 °C). Based on these significant properties, the integrated wearable gel sensor showed superior sensitivity (gauge factor = 3.11 at 25 °C and 2.01 at -20 °C) and could detect human activities with excellent accuracy and stability. It is expected that this work will provide a promising platform for fabricating and application of a high-sensitive strain conductive gel with long-term usage and stability.

3D-Printing of Silk Nanofibrils Reinforced Alginate for Soft Tissue Engineering.

The main challenge of extrusion 3D bioprinting is the development of bioinks with the desired rheological and mechanical performance and biocompatibility to create complex and patient-specific scaffolds in a repeatable and accurate manner. This study aims to introduce non-synthetic bioinks based on alginate (Alg) incorporated with various concentrations of silk nanofibrils (SNF, 1, 2, and 3 wt.%) and optimize their properties for soft tissue engineering. Alg-SNF inks demonstrated a high degree of shear-thinning with reversible stress softening behavior contributing to extrusion in pre-designed shapes. In addition, our results confirmed the good interaction between SNFs and alginate matrix resulted in significantly improved mechanical and biological characteristics and controlled degradation rate. Noticeably, the addition of 2 wt.% SNF improved the compressive strength (2.2 times), tensile strength (5 times), and elastic modulus (3 times) of alginate. In addition, reinforcing 3D-printed alginate with 2 wt.% SNF resulted in increased cell viability (1.5 times) and proliferation (5.6 times) after 5 days of culturing. In summary, our study highlights the favorable rheological and mechanical performances, degradation rate, swelling, and biocompatibility of Alg-2SNF ink containing 2 wt.% SNF for extrusion-based bioprinting.

Dentin extracellular matrix loaded bioactive glass/GelMA support rapid bone mineralization for potential pulp regeneration.

The study aims to develop a novel dentin extracellular matrix (dECM) loaded gelatin methacrylate (GelMA)-5 wt% bioactive glass (BG) (Gel-BG) hydrogel for dental pulp regeneration. We investigate the role of dECM content (2.5, 5, and 10 wt%) on the physicochemical characteristics and biological responses of Gel-BG hydrogel in contact with stem cells isolated from human exfoliated deciduous teeth (SHED). Results showed that the compressive strength of Gel-BG/dECM hydrogel significantly enhanced from 18.9 ± 0.5 kPa (at Gel-BG) to 79.8 ± 3.0 kPa after incorporation of 10 wt% dECM. Moreover, we found that in vitro bioactivity of Gel-BG improved and the degradation rate and swelling ratio reduced with increasing dECM content. The hybrid hydrogels also revealed effectual biocompatibility, >138 % cell viability after 7 days of culture; where Gel-BG/5%dECM was most suitable. In addition, the incorporation of 5 wt% dECM within Gel-BG considerably improved alkaline phosphatase (ALP) activity and osteogenic differentiation of SHED cells. Taken together, the novel bioengineered Gel-BG/dECM hydrogels having appropriate bioactivity, degradation rate, osteoconductive and mechanical properties represent the potential applications for clinical practice in the future.

Multifunctional Bioinspired Bredigite-Modified Adhesive for Bone Fracture Healing.

Despite recent advances in bone adhesives applied for full median sternotomy, the regeneration of bone defects has remained challenging since the healing process is hampered by poor adhesiveness, limited bioactivity, and lack of antibacterial functions. Bioinspired adhesives by marine organisms provide a novel concept to circumvent these problems. Herein, a dual cross-link strategy is employed in designing a multifaceted bioinspired adhesive consisting of a catechol amine-functionalized hyperbranched polymer (polydopamine-co-acrylate, PDA), bredigite (BR) nanoparticles, and Fe3+ ions. The hybrid adhesives exhibit strong adhesion to various substrates such as poly(methyl methacrylate), glass, bone, and skin tissues through synergy between irreversible covalent and reversible noncovalent cross-linking, depending on the BR content. Noticeably, the adhesion strength of hybrid adhesives containing 2 wt % BR nanoparticles to bone tissues is 2.3 ± 0.8 MPa, which is about 3 times higher than that of pure PDA adhesives. We also demonstrate that these hybrid adhesives not only are bioactive and accelerate in vitro bone-like apatite formation but also exhibit antibacterial properties against Staphylococcus aureus, depending on the BR concentration. Furthermore, the superior cellular responses in contact with hybrid adhesives, including improved human osteosarcoma MG63 cell spreading and osteogenic differentiation, are achieved owing to the appropriate ion release and flexibility of the cross-linked double-network adhesive. In summary, multifunctional hybrid PDA/BR adhesives with appreciable osteoconductive, mechanical, and antibacterial properties represent the potential applications for median sternotomy surgery as a bone tissue adhesive.

Advances in organosolv modified components occurring during the organosolv pretreatment of lignocellulosic biomass.

The valorization of organosolv pretreatment (OP) is a required approach to the industrialization of the current enzyme-mediated lignocellulosic biorefinery. Recent literature has demonstrated that the solvolysis happening in the OP can modify the soluble components into value-added active compounds, namely organosolv modified lignin (OML) and organosolv modified sugars (OMSs), in addition to protecting them against excessive degradation. Among them, the OML is coincidental with the "lignin-first" strategy that should render a highly reactive lignin enriched with ß-O-4 linkages and less condensed structure by organosolv grafting, which is desirable for the transformation into phenolic compounds. The OMSs are valuable glycosidic compounds mainly synthesized by trans-glycosylation, which can find potential applications in cosmetics, foods, and healthcare. Therefore, a state-of-the-art OP holds a big promise of lowering the process cost by the valorization of these active compounds. Recent advances in organosolv modified components are reviewed, and perspectives are made for addressing future challenges.

Zwitterionic keratin coating on silk-Laponite fibrous membranes for guided bone regeneration.

Implant-related infection is one of the main challenges in periodontal diseases. According to the zwitterionic properties of keratin, we aim to develop guided bone regeneration (GBR) membrane with antibacterial and bioactivity properties using a keratin coating. In this study, electrospun silk fibroin (SF)-Laponite (LAP) fibrous membranes were developed as GBR membranes, and keratin extracted from sheep wool was electrosprayed on them. Here, the role of electrospraying time (2, 3, and 4h) on the properties of the GBR membranes was investigated. After physicochemical characterization of the keratin-modified membranes, in vitro bioactivity and degradation rate of the membranes were studied in simulated body fluid and phosphate buffer saline, respectively. Moreover, proliferation and differentiation of mesenchymal stem cells were evaluated in contact with the keratin-modified SF-LAP membrane. Finally, the antibacterial activity of membranes against gram-positive bacteria (Staphylococcus aureus) was investigated. Results demonstrated the successful formation of homogeneous wool keratin coating on SF-LAP fibrous membranes using a simple electrospray process. While wool keratin coating significantly enhanced the elongation and hydrophilicity of the SF-LAP membrane, the mechanical strength was not changed. In addition, keratin coating significantly improved the bioactivity and degradation rate of SF-LAP membranes, owing to the carboxyl groups of amino acids in keratin coating. In addition, the synergic role of LAP nanoparticles and keratin coating drastically improved osteoblast proliferation and differentiation. Finally, the zwitterionic property of wool keratin coating originating from their equal positive (NH3 + ) and negative (COO- ) charges considerably improved the antibacterial activity of the SF-LAP membrane. Overall, keratin-coated SF-LAP fibrous membranes with significant mechanical and biological properties could have the potential for GBR membranes.

Layered scaffolds in periodontal regeneration.

Periodontitis is a common inflammatory disease in dentistry that may lead to tooth loss and aesthetic problems. Periodontal tissue has a sophisticated architecture including four sections of alveolar bone, cementum, gingiva, and periodontal ligament fiber; all these four can be damaged during periodontitis. Thus, for whole periodontal regeneration, it is important to form both hard and soft tissue structures simultaneously on the tooth root surface without forming junctional epithelium and ankylosis. This condition makes the treatment of the periodontium a challenging process. Various regenerative methods including Guided Bone/Tissue Regeneration (GBR/GTR) using various membranes have been developed. Although using such GBR/GTR membranes was successful for partial periodontal treatment, they cannot be used for the regeneration of complete periodontium. For this purpose, multilayered scaffolds are now being developed. Such scaffolds may include various biomaterials, stem cells, and growth factors in a multiphasic configuration in which each layer is designed to regenerate specific section of the periodontium. This article provides a comprehensive review of the multilayered scaffolds for periodontal regeneration based on natural or synthetic polymers, and their combinations with other biomaterials and bioactive molecules. After highlighting the challenges related to multilayered scaffolds preparation, features of suitable scaffolds for periodontal regeneration are discussed.

A Review on Antibacterial Biomaterials in Biomedical Applications: From Materials Perspective to Bioinks Design.

In tissue engineering, three-dimensional (3D) printing is an emerging approach to producing functioning tissue constructs to repair wounds and repair or replace sick tissue/organs. It allows for precise control of materials and other components in the tissue constructs in an automated way, potentially permitting great throughput production. An ink made using one or multiple biomaterials can be 3D printed into tissue constructs by the printing process; though promising in tissue engineering, the printed constructs have also been reported to have the ability to lead to the emergence of unforeseen illnesses and failure due to biomaterial-related infections. Numerous approaches and/or strategies have been developed to combat biomaterial-related infections, and among them, natural biomaterials, surface treatment of biomaterials, and incorporating inorganic agents have been widely employed for the construct fabrication by 3D printing. Despite various attempts to synthesize and/or optimize the inks for 3D printing, the incidence of infection in the implanted tissue constructs remains one of the most significant issues. For the first time, here we present an overview of inks with antibacterial properties for 3D printing, focusing on the principles and strategies to accomplish biomaterials with anti-infective properties, and the synthesis of metallic ion-containing ink, chitosan-containing inks, and other antibacterial inks. Related discussions regarding the mechanics of biofilm formation and antibacterial performance are also presented, along with future perspectives of the importance of developing printable inks.

Synergic role of zinc and gallium doping in hydroxyapatite nanoparticles to improve osteogenesis and antibacterial activity.

Recently, postoperative bone infections have been one of the most crucial challenges for surgeons. This study aims to synergistically promote antibacterial and osteoconductive properties of hydroxyapatite (HAp) nanoparticles through binary doping of Zn2+ and Ga3+ ions (Zn-Ga:HAp). Zn-Ga:HAp nanopowders with spherical morphology and homogeneous size are synthesized using a simple sol-gel method. Substitution of both zinc and gallium in the structure of HAp results in a gradual decrease in the lattice parameters as doping level increases, limits the growth of HAp particles and reduces its crystallinity. Noticeably, the crystallinity of HAp (85%) reduces to less than 73% (for XZn = 0.1), 78% (for XGa = 0.4) and 75% (for XZn = 0.1 and XGa = 0.4). Ion doping also significantly modulate the release of bioactive ions (Ca2+, PO43-, Zn2+, Ga3+) from the Zn-Ga:HAp depended on the overall amount of Ga and Zn in the HAp, which could mediate the biological responses. Incorporating both Zn2+ and Ga3+ ions in HAp structure could significantly improve the antibacterial activity of HAp nanopowders against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with a concentration-dependent effect. Noticeably, Zn-Ga:HAp (XZn = 0.1 and XGa = 0.4) powder shows the antibacterial activity of more than 68% and 84% against E. coli and S. aureus, respectively, at the concentration of 500 µg/ml, thereby showing excellent antibacterial properties. In addition, Zn-Ga:HAp nanopowders not only do not exhibit any cytotoxicity towards hMSCs, but also show significantly superior osteogenic properties. For instance, Zn-Ga:HAp (XZn = 0.1 and XGa = 0.4) nanopowders significantly enhance the alkaline phosphatase activity (approximately 2-fold) and mineralization (approximately 3-fold) of hMSCs after 14 days of culture, compared to pure HAp. Overall, Zn-Ga:HAp (XZn = 0.1 and XGa = 0.4) with desired osteogenesis and antibacterial activity compared to pure HAp, Zn:HAp and Ga:HAp shows promising opportunities for the implant-associated infections and the efficient healing of bone defects.

Cutting-Edge Progress in Stimuli-Responsive Bioadhesives: From Synthesis to Clinical Applications.

With the advent of "intelligent" materials, the design of smart bioadhesives responding to chemical, physical, or biological stimuli has been widely developed in biomedical applications to minimize the risk of wounds reopening, chronic pain, and inflammation. Intelligent bioadhesives are free-flowing liquid solutions passing through a phase shift in the physiological environment due to stimuli such as light, temperature, pH, and electric field. They possess great merits, such as ease to access and the ability to sustained release as well as the spatial transfer of a biomolecule with reduced side effects. Tissue engineering, wound healing, drug delivery, regenerative biomedicine, cancer therapy, and other fields have benefited from smart bioadhesives. Recently, many disciplinary attempts have been performed to promote the functionality of smart bioadhesives and discover innovative compositions. However, according to our knowledge, the development of multifunctional bioadhesives for various biomedical applications has not been adequately explored. This review aims to summarize the most recent cutting-edge strategies (years 2015-2021) developed for stimuli-sensitive bioadhesives responding to external stimuli. We first focus on five primary categories of stimuli-responsive bioadhesive systems (pH, thermal, light, electric field, and biomolecules), their properties, and limitations. Following the introduction of principal criteria for smart bioadhesives, their performances are discussed, and certain smart polymeric materials employed in their creation in 2015 are studied. Finally, advantages, disadvantages, and future directions regarding smart bioadhesives for biomedical applications are surveyed.

Strong and bioactive bioinspired biomaterials, next generation of bone adhesives.

The bone adhesive is a clinical requirement for complicated bone fractures always articulated by surgeons. Applying glue is a quick and easy way to fix broken bones. Adhesives, unlike conventional fixation methods such as wires and sutures, improve healing conditions and reduce postoperative pain by creating a complete connection at the fractured joint. Despite many efforts in the field of bone adhesives, the creation of a successful adhesive with robust adhesion and appropriate bioactivity for the treatment of bone fractures is still in its infancy. Because of the resemblance of the body's humid environment to the underwater environment, in the latest decades, researchers have pursued inspiration from nature to develop strong bioactive adhesives for bone tissue. The aim of this review article is to discuss the recent state of the art in bone adhesives with a specific focus on biomimetic adhesives, their action mechanisms, and upcoming perspective. Firstly, the adhesive biomaterials with specific affinity to bone tissue are introduced and their rational design is studied. Consequently, various types of synthetic and natural bioadhesives for bone tissue are comprehensively overviewed. Then, bioinspired-adhesives are described, highlighting relevant structures and examples of biomimetic adhesives mainly made of DOPA and the complex coacervates inspired by proteins secreted in mussel and sandcastle worms, respectively. Finally, this article overviews the challenges of the current bioadhesives and the future research for the improvement of the properties of biomimetic adhesives for use as bone adhesives.

Recent Advances in Designing Electroconductive Biomaterials for Cardiac Tissue Engineering.

Implantable cardiac patches and injectable hydrogels are among the most promising therapies for cardiac tissue regeneration following myocardial infarction. Incorporating electrical conductivity into these patches and hydrogels is found to be an efficient method to improve cardiac tissue function. Conductive nanomaterials such as carbon nanotube, graphene oxide, gold nanorod, as well as conductive polymers such as polyaniline, polypyrrole, and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate are appealing because they possess the electroconductive properties of semiconductors with ease of processing and have potential to restore electrical signaling propagation through the infarct area. Numerous studies have utilized these materials for regeneration of biological tissues that possess electrical activities, such as cardiac tissue. In this review, recent studies on the use of electroconductive materials for cardiac tissue engineering and their fabrication methods are summarized. Moreover, recent advances in developing electroconductive materials for delivering therapeutic agents as one of emerging approaches for treating heart diseases and regenerating damaged cardiac tissues are highlighted.