Industry 4.0-Compliant Occupational Chronic Obstructive Pulmonary Disease Prevention: Literature Review and Future Directions.

Chronic obstructive pulmonary disease (COPD) is among prevalent occupational diseases, causing early retirement and disabilities. This paper looks into occupational-related COPD prevention and intervention in the workplace for Industry 4.0-compliant occupation health and safety management. The economic burden and other severe problems caused by COPD are introduced. Subsequently, seminal research in relevant areas is reviewed. The prospects and challenges are introduced and discussed based on critical management approaches. An initial design of an Industry 4.0-compliant occupational COPD prevention system is presented at the end.

Recent Advances in Enzymatic and Non-Enzymatic Electrochemical Glucose Sensing.

The detection of glucose is crucial in the management of diabetes and other medical conditions but also crucial in a wide range of industries such as food and beverages. The development of glucose sensors in the past century has allowed diabetic patients to effectively manage their disease and has saved lives. First-generation glucose sensors have considerable limitations in sensitivity and selectivity which has spurred the development of more advanced approaches for both the medical and industrial sectors. The wide range of application areas has resulted in a range of materials and fabrication techniques to produce novel glucose sensors that have higher sensitivity and selectivity, lower cost, and are simpler to use. A major focus has been on the development of enzymatic electrochemical sensors, typically using glucose oxidase. However, non-enzymatic approaches using direct electrochemistry of glucose on noble metals are now a viable approach in glucose biosensor design. This review discusses the mechanisms of electrochemical glucose sensing with a focus on the different generations of enzymatic-based sensors, their recent advances, and provides an overview of the next generation of non-enzymatic sensors. Advancements in manufacturing techniques and materials are key in propelling the field of glucose sensing, however, significant limitations remain which are highlighted in this review and requires addressing to obtain a more stable, sensitive, selective, cost efficient, and real-time glucose sensor.

Conductive Polymeric-Based Electroactive Scaffolds for Tissue Engineering Applications: Current Progress and Challenges from Biomaterials and Manufacturing Perspectives.

The practice of combining external stimulation therapy alongside stimuli-responsive bio-scaffolds has shown massive potential for tissue engineering applications. One promising example is the combination of electrical stimulation (ES) and electroactive scaffolds because ES could enhance cell adhesion and proliferation as well as modulating cellular specialization. Even though electroactive scaffolds have the potential to revolutionize the field of tissue engineering due to their ability to distribute ES directly to the target tissues, the development of effective electroactive scaffolds with specific properties remains a major issue in their practical uses. Conductive polymers (CPs) offer ease of modification that allows for tailoring the scaffold's various properties, making them an attractive option for conductive component in electroactive scaffolds. This review provides an up-to-date narrative of the progress of CPs-based electroactive scaffolds and the challenge of their use in various tissue engineering applications from biomaterials perspectives. The general issues with CP-based scaffolds relevant to its application as electroactive scaffolds were discussed, followed by a more specific discussion in their applications for specific tissues, including bone, nerve, skin, skeletal muscle and cardiac muscle scaffolds. Furthermore, this review also highlighted the importance of the manufacturing process relative to the scaffold's performance, with particular emphasis on additive manufacturing, and various strategies to overcome the CPs' limitations in the development of electroactive scaffolds.

Green Synthesis of Silver Nanoparticles Using Extract of Cilembu Sweet Potatoes (Ipomoea batatas L var. Rancing) as Potential Filler for 3D Printed Electroactive and Anti-Infection Scaffolds.

Electroactive biomaterials are fascinating for tissue engineering applications because of their ability to deliver electrical stimulation directly to cells, tissue, and organs. One particularly attractive conductive filler for electroactive biomaterials is silver nanoparticles (AgNPs) because of their high conductivity, antibacterial activity, and ability to promote bone healing. However, production of AgNPs involves a toxic reducing agent which would inhibit biological scaffold performance. This work explores facile and green synthesis of AgNPs using extract of Cilembu sweet potato and studies the effect of baking and precursor concentrations (1, 10 and 100 mM) on AgNPs' properties. Transmission electron microscope (TEM) results revealed that the smallest particle size of AgNPs (9.95 ± 3.69 nm) with nodular morphology was obtained by utilization of baked extract and ten mM AgNO3. Polycaprolactone (PCL)/AgNPs scaffolds exhibited several enhancements compared to PCL scaffolds. Compressive strength was six times greater (3.88 ± 0.42 MPa), more hydrophilic (contact angle of 76.8 ± 1.7°), conductive (2.3 ± 0.5 × 10-3 S/cm) and exhibited anti-bacterial properties against Staphylococcus aureus ATCC3658 (99.5% reduction of surviving bacteria). Despite the promising results, further investigation on biological assessment is required to obtain comprehensive study of this scaffold. This green synthesis approach together with the use of 3D printing opens a new route to manufacture AgNPs-based electroactive with improved anti-bacterial properties without utilization of any toxic organic solvents.

Cell therapy with human MSCs isolated from the umbilical cord Wharton jelly associated to a PVA membrane in the treatment of chronic skin wounds.

The healing process of the skin is a dynamic procedure mediated through a complex feedback of growth factors secreted by a variety of cells types. Despite the most recent advances in wound healing management and surgical procedures, these techniques still fail up to 50%, so cellular therapies involving mesenchymal stem cells (MSCs) are nowadays a promising treatment of skin ulcers which are a cause of high morbidity. The MSCs modulate the inflammatory local response and induce cell replacing, by a paracrine mode of action, being an important cell therapy for the impaired wound healing. The local application of human MSCs (hMSCs) isolated from the umbilical cord Wharton's jelly together with a poly(vinyl alcohol) hydrogel (PVA) membrane, was tested to promote wound healing in two dogs that were referred for clinical examination at UPVET Hospital, showing non-healing large skin lesions by the standard treatments. The wounds were infiltrated with 1000 cells/µl hMSCs in a total volume of 100 µl per cm(2) of lesion area. A PVA membrane was applied to completely cover the wound to prevent its dehydration. Both animals after the treatment demonstrated a significant progress in skin regeneration with decreased extent of ulcerated areas confirmed by histological analysis. The use of Wharton's jelly MSCs associated with a PVA membrane showed promising clinical results for future application in the treatment of chronic wounds in companion animals and humans.

The effect of graphene and graphene oxide induced reactive oxygen species on polycaprolactone scaffolds for bone cancer applications.

Bone cancer remains a critical healthcare problem. Among current clinical treatments, tumour resection is the most common strategy. It is usually effective but may present several limitations such as multiple operations, long hospital time, and the potential recurrence caused by the incomplete removal of cancer cells. To address these limitations, three-dimensional (3D) scaffolds fabricated through additive manufacturing have been researched for both bone cancer treatment and post-treatment rehabilitation. Polycaprolactone (PCL)-based scaffolds play an important role in bone regeneration, serving as a physical substrate to fill the defect site, recruiting cells, and promoting cell proliferation and differentiation, ultimately leading to the regeneration of the bone tissue without multiple surgical applications. Multiple advanced materials have been incorporated during the fabrication process to improve certain functions and/or modulate biological performances. Graphene-based nanomaterials, particularly graphene (G) and graphene oxide (GO), have been investigated both in vitro and in vivo, significantly improving the scaffold's physical, chemical, and biological properties, which strongly depend on the material type and concentration. A unique targeted inhibition effect on cancer cells was also discovered. However, limited research has been conducted on utilising graphene-based nanomaterials for both bone regeneration and bone cancer treatment, and there is no systematic study into the material- and dose-dependent effects, as well as the working mechanism on 3D scaffolds to realise these functions. This paper addresses these limitations by designing and fabricating PCL-based scaffolds containing different concentrations of G and GO and assessing their biological behaviour correlating it to the reactive oxygen species (ROS) release level. Results suggest that the ROS release from the scaffolds is a dominant mechanism that affects the biological behaviour of the scaffolds. ROS release also contributes to the inhibition effect on bone cancer due to healthy cells and cancer cells responding differently to ROS, and the osteogenesis results also present a certain correlation with ROS. These observations revealed a new route for realising bone cancer treatment and subsequent new bone regeneration, using a single dual-functional 3D scaffold.

Self-Healable and 4D Printable Hydrogel for Stretchable Electronics.

Materials with high stretchability and conductivity are used to fabricate stretchable electronics. Self-healing capability and four-dimensional (4D) printability are becoming increasingly important for these materials to facilitate their recovery from damage and endow them with stimuli-response properties. However, it remains challenging to design a single material that combines these four strengths. Here, a dually crosslinked hydrogel is developed by combining a covalently crosslinked acrylic acid (AAC) network and Fe3+ ions through dynamic and reversible ionically crosslinked coordination. The remarkable electrical sensitivity (a gauge factor of 3.93 under a strain of 1500%), superior stretchability (a fracture strain up to 1700%), self-healing ability (a healing efficiency of 88% and 97% for the mechanical and electrical properties, respectively), and 4D printability of the hydrogel are demonstrated by constructing a strain sensor, a two-dimensional touch panel, and shape-morphing structures with water-responsive behavior. The hydrogel demonstrates vast potential for applications in stretchable electronics.

Biomimetic dual sensing polymer nanocomposite for biomedical applications.

There is a growing need for sensing materials that can provide multiple sensing capabilities for wearable devices, implantable sensors, and diagnostics tools. As complex human physiology requires materials that can simultaneously detect and respond to slow and fast pressure fluctuations. Mimicking the slow adaptive (SA) and fast adaptive (FA) mechanoreceptors in skin can lead to the development of dual sensing electrospun polymer nanocomposites for biomedical applications. These dual sensing nanocomposites can provide simultaneous sensing of both slow and fast pressure fluctuations, making them ideal for applications such as monitoring vital signs, detecting a wider range of movements and pressures. Here we develop a novel dual sensing PVDF-HFP-based nanocomposite that combines the advantages of capacitive and piezoelectric properties through controling electrospinning environment and processing parameters, polymer solution composition, and addition of nucleating agents such as Carbon Black (CB) to enhance the crystalline development of ß-phase, fibre thickness, and morphology. The developed PVDF-HFP/CB nanocomposite presents and response to both slow and fast pressure fluctuations with high capacitance (5.37 nF) and output voltage (1.51 V) allowing for accurate and reliable measurements.

Recent Advances in 4D Printing of Advanced Materials and Structures for Functional Applications.

4D printing has attracted tremendous worldwide attention during the past decade. This technology enables the shape, property, or functionality of printed structures to change with time in response to diverse external stimuli, making the original static structures alive. The revolutionary 4D-printing technology offers remarkable benefits in controlling geometric and functional reconfiguration, thereby showcasing immense potential across diverse fields, including biomedical engineering, electronics, robotics, and photonics. Here, a comprehensive review of the latest achievements in 4D printing using various types of materials and different additive manufacturing techniques is presented. The state-of-the-art strategies implemented in harnessing various 4D-printed structures are highlighted, which involve materials design, stimuli, functionalities, and applications. The machine learning approach explored for 4D printing is also discussed. Finally, the perspectives on the current challenges and future trends toward further development in 4D printing are summarized.

In Vitro Evaluation of Pore Size Graded Bone Scaffolds with Different Material Composition.

The demand for biomimetic and biocompatible scaffolds in equivalence of structure and material composition for the regeneration of bone tissue is relevantly high. This article is investigating a novel three-dimensional (3D) printed porous structure called bone bricks with a gradient pore size mimicking the structure of the bone tissue. Poly-ɛ-caprolactone (PCL) combined with ceramics such as hydroxyapatite (HA), ß-tricalcium phosphate (TCP), and bioglass 45S5 were successfully mixed using a melt blending method and fabricated with the use of screw-assisted extrusion-based additive manufacturing system. Bone bricks containing the same material concentration (20 wt%) were biologically characterized through proliferation and differentiation tests. Scanning electron microscopy (SEM) was used to investigate the morphology of cells on the surface of bone bricks, whereas energy dispersive X-ray (EDX) spectroscopy was used to investigate the element composition on the surface of the bone bricks. Confocal imaging was used to investigate the number of differentiated cells on the surface of bone bricks. Proliferation results showed that bone bricks containing PCL/HA content are presenting higher proliferation properties, whereas differentiation results showed that bone bricks containing PCL/Bioglass 45S5 are presenting higher differentiation properties. Confocal imaging results showed that bone bricks containing PCL/Bioglass 45S5 are presenting a higher number of differentiated cells on their surface compared with the other material contents.

Multi-Stage Thermal Modelling of Extrusion-Based Polymer Additive Manufacturing.

Additive manufacturing is one the most promising fabrication strategies for the fabrication of bone tissue scaffolds using biodegradable semi-crystalline polymers. During the fabrication process, polymeric material in a molten state is deposited in a platform and starts to solidify while cooling down. The build-up of consecutive layers reheats the previously deposited material, introducing a complex thermal cycle with impacts on the overall properties of printed scaffolds. Therefore, the accurate prediction of these thermal cycles is significantly important to properly design the additively manufactured polymer scaffolds and the bonding between the layers. This paper presents a novel multi-stage numerical model, integrating a 2D representation of the dynamic deposition process and a 3D thermal evolution model to simulate the fabrication process. Numerical simulations show how the deposition velocity controls the spatial dimensions of the individual deposition layers and the cooling process when consecutive layers are deposited during polymer printing. Moreover, numerical results show a good agreement with experimental results.

A systematic review of the application of immersive technologies for safety and health management in the construction sector.

INTRODUCTION: The construction industry employs about 7% of global manpower and contributes about 6% to the global economy. However, statistics have depicted that the construction industry contributes significantly to workplace fatalities and injuries despite multiple interventions (including technological applications) implemented by governments and construction companies. Recently, immersive technologies as part of a suite of industry 4.0 technologies, have also strongly emerged as a viable pathway to help address poor construction occupational safety and health (OSH) performance. METHOD: With the aim of gaining a broad view of different construction OSH issues addressed using immersive technologies, a review on the application of immersive technologies for construction OSH management is conducted using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) approach and bibliometric analysis of literature. This resulted in the evaluation of 117 relevant papers collected from three online databases (Scopus, Web of Science, and Engineering Village). RESULTS: The review revealed that literature have focused on the application of various immersive technologies for hazard identification and visualization, safety training, design for safety, risk perception, and assessment in various construction works. The review identified several limitations regarding the use of immersive technologies, which include the low level of adoption of the developed immersive technologies for OSH management by the construction industry, very limited research on the application of immersive technologies for health hazards, and limited focus on the comparison of the effectiveness of various immersive technologies for construction OSH management. CONCLUSIONS AND PRACTICAL APPLICATIONS: For future research, it is recommended to identify possible reasons for the low transition level from research to industry practice and proffer solutions to the identified issues. Another recommendation is the study of the effectiveness of the use of immersive technologies for addressing health hazards in comparison to the conventional methods.

Early In Vivo Osteogenic and Inflammatory Response of 3D Printed Polycaprolactone/Carbon Nanotube/Hydroxyapatite/Tricalcium Phosphate Composite Scaffolds.

The development of advanced biomaterials and manufacturing processes to fabricate biologically and mechanically appropriate scaffolds for bone tissue is a significant challenge. Polycaprolactone (PCL) is a biocompatible and degradable polymer used in bone tissue engineering, but it lacks biofunctionalization. Bioceramics, such as hydroxyapatite (HA) and ß tricalcium phosphate (ß-TCP), which are similar chemically to native bone, can facilitate both osteointegration and osteoinduction whilst improving the biomechanics of a scaffold. Carbon nanotubes (CNTs) display exceptional electrical conductivity and mechanical properties. A major limitation is the understanding of how PCL-based scaffolds containing HA, TCP, and CNTs behave in vivo in a bone regeneration model. The objective of this study was to evaluate the use of three-dimensional (3D) printed PCL-based composite scaffolds containing CNTs, HA, and ß-TCP during the initial osteogenic and inflammatory response phase in a critical bone defect rat model. Gene expression related to early osteogenesis, the inflammatory phase, and tissue formation was evaluated using quantitative real-time PCR (RT-qPCR). Tissue formation and mineralization were assessed by histomorphometry. The CNT+HA/TCP group presented higher expression of osteogenic genes after seven days. The CNT+HA and CNT+TCP groups stimulated higher gene expression for tissue formation and mineralization, and pro- and anti-inflammatory genes after 14 and 30 days. Moreover, the CNT+TCP and CNT+HA/TCP groups showed higher gene expressions related to M1 macrophages. The association of CNTs with ceramics at 10wt% (CNT+HA/TCP) showed lower expressions of inflammatory genes and higher osteogenic, presenting a positive impact and balanced cell signaling for early bone formation. The association of CNTs with both ceramics promoted a minor inflammatory response and faster bone tissue formation.

Electrical Stimulation Therapy and HA/TCP Composite Scaffolds Modulate the Wnt Pathways in Bone Regeneration of Critical-Sized Defects.

Critical bone defects are the most difficult challenges in the area of tissue repair. Polycaprolactone (PCL) scaffolds, associated with hydroxyapatite (HA) and tricalcium phosphate (TCP), are reported to have an enhanced bioactivity. Moreover, the use of electrical stimulation (ES) has overcome the lack of bioelectricity at the bone defect site and compensated the endogenous electrical signals. Such treatments could modulate cells and tissue signaling pathways. However, there is no study investigating the effects of ES and bioceramic composite scaffolds on bone tissue formation, particularly in the view of cell signaling pathway. This study aims to investigate the application of HA/TCP composite scaffolds and ES and their effects on the Wingless-related integration site (Wnt) pathway in critical bone repair. Critical bone defects (25 mm2) were performed in rats, which were divided into four groups: PCL, PCL + ES, HA/TCP and HA/TCP + ES. The scaffolds were grafted at the defect site and applied with the ES application twice a week using 10 µA of current for 5 min. Bone samples were collected for histomorphometry, immunohistochemistry and molecular analysis. At the Wnt canonical pathway, HA/TCP and HA/TCP + ES groups showed higher Wnt1 and ß-catenin gene expression levels, especially HA/TCP. Moreover, HA/TCP + ES presented higher Runx2, Osterix and Bmp-2 levels. At the Wnt non-canonical pathway, HA/TCP group showed higher voltage-gated calcium channel (Vgcc), calmodulin-dependent protein kinase II, and Wnt5a genes expression, while HA/TCP + ES presented higher protein expression of VGCC and calmodulin (CaM) at the same period. The decrease in sclerostin and osteopontin genes expressions and the lower bone sialoprotein II in the HA/TCP + ES group may be related to the early bone remodeling. This study shows that the use of ES modulated the Wnt pathways and accelerated the osteogenesis with improved tissue maturation.

Accelerated Degradation of Poly-ε-caprolactone Composite Scaffolds for Large Bone Defects.

This research investigates the accelerated hydrolytic degradation process of both anatomically designed bone scaffolds with a pore size gradient and a rectangular shape (biomimetically designed scaffolds or bone bricks). The effect of material composition is investigated considering poly-ε-caprolactone (PCL) as the main scaffold material, reinforced with ceramics such as hydroxyapatite (HA), ß-tricalcium phosphate (TCP) and bioglass at a concentration of 20 wt%. In the case of rectangular scaffolds, the effect of pore size (200 µm, 300 µm and 500 µm) is also investigated. The degradation process (accelerated degradation) was investigated during a period of 5 days in a sodium hydroxide (NaOH) medium. Degraded bone bricks and rectangular scaffolds were measured each day to evaluate the weight loss of the samples, which were also morphologically, thermally, chemically and mechanically assessed. The results show that the PCL/bioglass bone brick scaffolds exhibited faster degradation kinetics in comparison with the PCL, PCL/HA and PCL/TCP bone bricks. Furthermore, the degradation kinetics of rectangular scaffolds increased by increasing the pore size from 500 µm to 200 µm. The results also indicate that, for the same material composition, bone bricks degrade slower compared with rectangular scaffolds. The scanning electron microscopy (SEM) images show that the degradation process was faster on the external regions of the bone brick scaffolds (600 µm pore size) compared with the internal regions (200 µm pore size). The thermal gravimetric analysis (TGA) results show that the ceramic concentration remained constant throughout the degradation process, while differential scanning calorimetry (DSC) results show that all scaffolds exhibited a reduction in crystallinity (Xc), enthalpy (Δm) and melting temperature (Tm) throughout the degradation process, while the glass transition temperature (Tg) slightly increased. Finally, the compression results show that the mechanical properties decreased during the degradation process, with PCL/bioglass bone bricks and rectangular scaffolds presenting higher mechanical properties with the same design in comparison with the other materials.

Poly-ε-Caprolactone 3D-Printed Porous Scaffold in a Femoral Condyle Defect Model Induces Early Osteo-Regeneration.

Large bone reconstruction following trauma poses significant challenges for reconstructive surgeons, leading to a healthcare burden for health systems, long-term pain for patients, and complex disorders such as infections that are difficult to resolve. The use of bone substitutes is suboptimal for substantial bone loss, as they induce localized atrophy and are generally weak, and unable to support load. A combination of strong polycaprolactone (PCL)-based scaffolds, with an average channel size of 330 µm, enriched with 20% w/w of hydroxyapatite (HA), ß-tricalcium phosphate (TCP), or Bioglass 45S5 (Bioglass), has been developed and tested for bone regeneration in a critical-size ovine femoral condyle defect model. After 6 weeks, tissue ingrowth was analyzed using X-ray computed tomography (XCT), Backscattered Electron Microscopy (BSE), and histomorphometry. At this point, all materials promoted new bone formation. Histological analysis showed no statistical difference among the different biomaterials (p > 0.05), but PCL-Bioglass scaffolds enhanced bone formation in the center of the scaffold more than the other types of materials. These materials show potential to promote bone regeneration in critical-sized defects on load-bearing sites.

Crystal Growth of 3D Poly(ε-caprolactone) Based Bone Scaffolds and Its Effects on the Physical Properties and Cellular Interactions.

Extrusion additive manufacturing is widely used to fabricate polymer-based 3D bone scaffolds. However, the insight views of crystal growths, scaffold features and eventually cell-scaffold interactions are still unknown. In this work, melt and solvent extrusion additive manufacturing techniques are used to produce scaffolds considering highly analogous printing conditions. Results show that the scaffolds produced by these two techniques present distinct physiochemical properties, with melt-printed scaffolds showing stronger mechanical properties and solvent-printed scaffolds showing rougher surface, higher degradation rate, and faster stress relaxation. These differences are attributed to the two different crystal growth kinetics, temperature-induced crystallization (TIC) and strain-induced crystallization (SIC), forming large/integrated spherulite-like and a small/fragmented lamella-like crystal regions respectively. The stiffer substrate of melt-printed scaffolds contributes to higher ratio of nuclear Yes-associated protein (YAP) allocation, favoring cell proliferation and differentiation. Faster relaxation and degradation of solvent-printed scaffolds result in dynamic surface, contributing to an early-stage faster osteogenesis differentiation.

Modelling and Simulation of MuCell®: The Effect of Key Processing Parameters on Cell Size and Weight Reduction.

Microcellular injection moulding is an important injection moulding technique to create foaming plastic parts. However, there are no consistent conclusions on the impact of processing parameters on the cell morphology of microcellular injection moulded parts. This paper investigates the influence of the main processing parameters, such as melt temperature, mould temperature, injection pressure, flow rate, shot volume and gas dosage amount, on the average cell size and weight reduction of a talc-reinforced polypropylene square part (165 mm × 165 mm × 3.2 mm), using the commercial software Moldex 3D. The effect of each parameter is investigated considering a range of values and the simulation results were compared with published experimental results. The differences between numerical and experimental trends are discussed.

3D printed scaffold design for bone defects with improved mechanical and biological properties.

Bone defect treatment is still a challenge in clinics, and synthetic bone scaffolds with adequate mechanical and biological properties are highly needed. Adequate waste and nutrient exchange of the implanted scaffold with the surrounded tissue is a major concern. Moreover, the risk of mechanical instability in the defect area during regular activity increases as the defect size increases. Thus, scaffolds with better mass transportation and mechanical properties are desired. This study introduces 3D printed polymeric scaffolds with a continuous pattern, ZigZag-Spiral pattern, for bone defects treatments. This pattern has a uniform distribution of pore size, which leads to uniform distribution of wall shear stress which is crucial for uniform differentiation of cells attached to the scaffolds. The mechanical, mass transportation, and biological properties of the 3D printed scaffolds are evaluated. The results show that the presented scaffolds have permeability similar to natural bone and, with the same porosity level, have higher mechanical properties than scaffolds with conventional lay-down patterns 0-90° and 0-45°. Finally, human mesenchymal stem cells are seeded on the scaffolds to determine the effects of geometrical microstructure on cell attachment and morphology. The results show that cells in scaffold with ZigZag-Spiral pattern infilled pores gradually, while the other patterns need more time to fill the pores. Considering mechanical, transportation, and biological properties of the considered patterns, scaffolds with ZigZag-Spiral patterns can mimic the properties of cancellous bones and be a better choice for treatments of bone defects.

Honey: An Advanced Antimicrobial and Wound Healing Biomaterial for Tissue Engineering Applications.

Honey was used in traditional medicine to treat wounds until the advent of modern medicine. The rising global antibiotic resistance has forced the development of novel therapies as alternatives to combat infections. Consequently, honey is experiencing a resurgence in evaluation for antimicrobial and wound healing applications. A range of both Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains and biofilms, are inhibited by honey. Furthermore, susceptibility to antibiotics can be restored when used synergistically with honey. Honey's antimicrobial activity also includes antifungal and antiviral properties, and in most varieties of honey, its activity is attributed to the enzymatic generation of hydrogen peroxide, a reactive oxygen species. Non-peroxide factors include low water activity, acidity, phenolic content, defensin-1, and methylglyoxal (Leptospermum honeys). Honey has also been widely explored as a tissue-regenerative agent. It can contribute to all stages of wound healing, and thus has been used in direct application and in dressings. The difficulty of the sustained delivery of honey's active ingredients to the wound site has driven the development of tissue engineering approaches (e.g., electrospinning and hydrogels). This review presents the most in-depth and up-to-date comprehensive overview of honey's antimicrobial and wound healing properties, commercial and medical uses, and its growing experimental use in tissue-engineered scaffolds.