Teicoplanin-Decorated Reduced Graphene Oxide Incorporated Silk Protein Hybrid Hydrogel for Accelerating Infectious Diabetic Wound Healing and Preventing Diabetic Foot Osteomyelitis.

Developing hybrid hydrogel dressings with anti-inflammatory, antioxidant, angiogenetic, and antibiofilm activities with higher bone tissue penetrability to accelerate diabetic wound healing and prevent diabetic foot osteomyelitis (DFO) is highly desirable in managing diabetic wounds. Herein, the glycopeptide teicoplanin is used for the first time as a green reductant to chemically reduce graphene oxide (GO). The resulting teicoplanin-decorated reduced graphene oxide (rGO) is incorporated into a mixture of silk proteins (SP) and crosslinked with genipin to yield a physicochemically crosslinked rGO-SP hybrid hydrogel. This hybrid hydrogel exhibits high porosity, self-healing, shear-induced thinning, increased cell proliferation and migration, and mechanical properties suitable for tissue engineering. Moreover, the hybrid hydrogel eradicates bacterial biofilms with a high penetrability index in agar and hydroxyapatite disks covered with biofilms, mimicking bone tissue. In vivo, the hybrid hydrogel accelerates the healing of noninfected wounds in a diabetic rat and infected wounds in a diabetic mouse by upregulating anti-inflammatory cytokines and downregulating matrix metalloproteinase-9, promoting M2 macrophage polarization and angiogenesis. The implantation of hybrid hydrogel into the infected site of mouse tibia improves bone regeneration. Hence, the rGO-SP hybrid hydrogel can be a promising wound dressing for treating infectious diabetic wounds, providing a further advantage in preventing DFO.

Nanocellulose-Based Hybrid Scaffolds for Skin and Bone Tissue Engineering: A 10-Year Overview.

Cellulose, the most abundant polymer on Earth, has been widely utilized in its nanoform due to its excellent properties, finding applications across various scientific fields. As the demand for nanocellulose continues to rise and its ease of use becomes apparent, there has been a significant increase in research publications centered on this biomaterial. Nanocellulose, in its different forms, has shown tremendous promise as a tissue engineered scaffold for regeneration and repair. Particularly, nanocellulose-based composites and scaffolds have emerged as highly demanding materials for both soft and hard tissue engineering. Medical practitioners have traditionally relied on collagen and its analogue, gelatin, for treating tissue damage. However, the limited mechanical strength of these biopolymers restricts their direct use in various applications. This issue can be overcome by making hybrids of these biopolymers with nanocellulose. This review presents a comprehensive analysis of the recent and most relevant publications focusing on hybrid composites of collagen and gelatin with a specific emphasis on their combination with nanocellulose. While bone and skin tissue engineering represents two areas where a majority of researchers are concentrating their efforts, this review highlights the use of nanocellulose-based hybrids in these contexts.

An antibacterial biologic patch based on bacterial cellulose for repair of infected hernias.

Infection-associated complications and repair failures and antibiotic resistance have emerged as a formidable challenge in hernia repair surgery. Consequently, the development of antibiotic-free antibacterial patches for hernia repair has become an exigent clinical necessity. Herein, a GBC/Gel/LL37 biological patch (biopatch) with exceptional antibacterial properties is fabricated by grafting 2-Methacryloyloxyethyl trimethylammonium chloride (METAC), a unique quaternary ammonium salt with vinyl, onto bacterial cellulose (GBC), followed by compounding with gelatin (Gel) and LL37. The GBC/Gel/LL37 biopatch exhibits stable swelling capacity, remarkable mechanical properties, flexibility, and favorable biocompatibility. The synergistic effect of METAC and LL37 confers upon the GBC/Gel/LL37 biopatch excellent antibacterial efficacy against Staphylococcus aureus and Escherichia coli, effectively eliminating invading bacteria without the aid of exogenous antibiotics in vivo while significantly reducing local acute inflammation caused by infection. Furthermore, the practical efficacy of the GBC/Gel/LL37 biopatch is evaluated in an infected ventral hernia model, revealing that the GBC/Gel/LL37 biopatch can prevent the formation of visceral adhesions, facilitate the repair of infected ventral hernia, and effectively mitigate chronic inflammation. The prepared antibacterial GBC/Gel/LL37 biopatch is very effective in dealing with the risk of infection in hernia repair surgery and offers potential clinical opportunities for other soft injuries, exhibiting considerable clinical application prospects.

Microneedle-mediated drug delivery for scar prevention and treatment.

Scars are an inevitable natural outcome of most wound healing processes and affect skin functions, leading to cosmetic, psychological and social problems. Several strategies, including surgery, radiation, cryotherapy, laser therapy, pressure therapy and corticosteroids, can be used to either prevent or treat scars. However, these strategies are ineffective, have side effects and are typically expensive. Microneedle (MN) technology is a powerful, minimally invasive platform for transdermal drug delivery. This review discusses the most recent progress in MN-mediated drug delivery to prevent and treat pathological scars (hypertrophic and keloids). A comprehensive overview of existing challenges and future perspectives is also provided.

Microneedle-based cell delivery and cell sampling for biomedical applications.

Cell-based therapeutics are novel therapeutic strategies that can potentially treat many presently incurable diseases through novel mechanisms of action. Cell therapies may benefit from the ease, safety, and efficacy of administering therapeutic cells. Despite considerable recent technological and biological advances, several barriers remain to the clinical translation and commercialization of cell-based therapies, including low patient compliance, personal handling inconvenience, poor biosafety, and limited biocompatibility. Microneedles (MNs) are emerging as a promising biomedical device option for improved cell delivery with little invasion, pain-free administration, and simplicity of disposal. MNs have shown considerable promise in treating a wide range of diseases and present the potential to improve cell-based therapies. In this review, we first summarized the latest advances in the various types of MNs developed for cell delivery and cell sampling. Emphasis was given to the design and fabrication of various types of MNs based on their structures and materials. Then we focus on the recent biomedical applications status of MNs-mediated cell delivery and sampling, including tissue repair (wound healing, heart repair, and endothelial repair), cancer treatment, diabetes therapy, cell sampling, and other applications. Finally, the current status of clinical application, potential perspectives, and the challenges for clinical translation are also highlighted.

Decorated bacteria-cellulose ultrasonic metasurface.

Cellulose, as a component of green plants, becomes attractive for fabricating biocompatible flexible functional devices but is plagued by hydrophilic properties, which make it easily break down in water by poor mechanical stability. Here we report a class of SiO2-nanoparticle-decorated bacteria-cellulose meta-skin with superior stability in water, excellent machining property, ultrathin thickness, and active bacteria-repairing capacity. We further develop functional ultrasonic metasurfaces based on meta-skin paper-cutting that can generate intricate patterns of ~10 µm precision. Benefited from the perfect ultrasound insulation of surface Cassie-Baxter states, we utilize meta-skin paper-cutting to design and fabricate ultrathin (~20 µm) and super-light (<20 mg) chip-scale devices, such as nonlocal holographic meta-lens and the 3D imaging meta-lens, realizing complicated acoustic holograms and high-resolution 3D ultrasound imaging in far fields. The decorated bacteria-cellulose ultrasonic metasurface opens the way for exploiting flexible and biologically degradable metamaterial devices with functionality customization and key applications in advanced biomedical engineering technologies.

Engineering homologous platelet-rich plasma, platelet-rich plasma-derived exosomes, and mesenchymal stem cell-derived exosomes-based dual-crosslinked hydrogels as bioactive diabetic wound dressings.

The management of diabetic wounds remains a critical therapeutic challenge. Platelet-rich plasma (PRP) gel, PRP-derived exosomes (PRP-Exos), and mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated therapeutic potential in wound treatment. Unfortunately, their poor mechanical properties, the short half-lives of growth factors (GFs), and the burst release of GFs and exosomes have limited their clinical applications. Furthermore, proteases in diabetic wounds degrade GFs, which hampers wound repair. Silk fibroin is an enzyme-immobilization biomaterial that could protect GFs from proteases. Herein, we developed novel dual-crosslinked hydrogels based on silk protein (SP) (sericin and fibroin), including SP@PRP, SP@MSC-Exos, and SP@PRP-Exos, to promote diabetic wound healing synergistically. SP@PRP was prepared from PRP and SP using calcium gluconate/thrombin as agonist, while SP@PRP-Exos and SP@MSC-Exos were derived from exosomes and SP with genipin as crosslinker. SP provided improved mechanical properties and enabled the sustained release of GFs and exosomes, thereby overcoming the limitations of PRP and exosomes in wound healing. The dual-crosslinked hydrogels displayed shear-induced thinning, self-healing, and eradication of microbial biofilms in a bone-mimicking environment. In vivo, the dual-crosslinked hydrogels contributed to faster diabetic wound healing than PRP and SP by upregulating GFs expression, down-regulating matrix metalloproteinase-9 expression, and by promoting an anti-NETotic effect, angiogenesis, and re-epithelialization. Hence, these dual-crosslinked hydrogels have the potential to be translated into a new generation of diabetic wound dressings.

The versatility of nanocellulose, modification strategies, and its current progress in wastewater treatment and environmental remediation.

Deterioration in the environmental ecosystems through the depletion of nonrenewable resources and the burden of deleterious contaminants is considered a global concern. To this end, great interest has been shown in the use of renewable and environmentally-friendly reactive materials dually to promote environmental sustainability and cope with harmful contaminants. Among the different available options, the use of nanocellulose (NC) as an environmentally benign and renewable natural nanomaterial is an attractive candidate for environmental remediation owing to its miraculous physicochemical characteristics. This review discusses the intrinsic properties and the structural aspects of different types of NC, including cellulose nanofibrils (CNFs), cellulose nanocrystals (CNCs), and bacterial cellulose (BC) or bacterial nanocellulose (BNC). Also, the different modification strategies involving the functionalization or hybridization of NC by using different functional and reactive materials aimed at wastewater remediation have been elaborated. The modified or hybridized NC has been explored for its applications in the removal or degradation of aquatic contaminants through adsorption, filtration, coagulation, catalysis, photocatalysis, and pollutant sensing. This review highlights the role of NC in the modified composites and describes the underlying mechanisms involved in the removal of contaminants. The life-cycle assessment (LCA) of NC is discussed to unveil the hidden risks associated with its production to the final disposal. Moreover, the contribution of NC in the promotion of waste management at different stages has been described in the form of the five-Rs strategy. In summary, this review provides rational insights to develop NC-based environmentally-friendly reactive materials for the removal and degradation of hazardous aquatic contaminants.

Cellulose hydrogel-based biodegradable and recyclable magnetoelectric composites for electromechanical conversion.

Flexible electromechanical conversion devices have attracted enormous attention as energy harvesters and self-powered sensors in the fields of wearable electronics and robotics. However, current flexible devices composed of plastic polymers and metals suffer from non-degradability and limited recyclability. Herein, a biodegradable and recyclable hydrogel-based magnetoelectric (ME) composite is fabricated via introducing NdFeB magnetic particles and copper wires into the regenerated bacterial cellulose (rBC) hydrogel. The developed hydrogel-based ME composites can effectively convert the mechanical kinetic energy into electrical energy based on the principle of electromagnetic induction, which maximum voltage reaches 15 µV. In addition, degradation experiments are conducted in this work to demonstrate the hydrogel can be rapidly degraded within 3 h under the condition of enzyme and completely natural degraded within 49 days in water, respectively. Moreover, the left NdFeB particles and copper wires can be recyclable and reused for the same devices, leaving no environmentally hazardous electronic waste.

Polymeric microneedles for enhanced drug delivery in cancer therapy.

Microneedles (MNs) have attracted the interest of researchers. Polymeric MNs offer tremendous promise as drug delivery vehicles for bio-applications because of their high loading capacity, strong patient adherence, excellent biodegradability and biocompatibility, low toxicity, and extremely cheap cost. Incorporating enhanced-property nanomaterials into polymeric MNs matrix increases their features such as better mechanical strength, sustained drug delivery, lower toxicity, and higher therapeutic effects, therefore considerably increasing their biomedical application. This paper discusses polymeric MN fabrication techniques and the present status of polymeric MNs as a delivery method for enhanced drug delivery in cancer therapeutic applications. Furthermore, the opportunities and challenges of polymeric MNs for improved drug delivery in cancer therapy are highlighted.

In Situ Synthesized Porous Bacterial Cellulose/Poly(vinyl alcohol)-Based Silk Sericin and Azithromycin Release System for Treating Chronic Wound Biofilm.

Chronic wounds are associated with infectious microbial complex communities called biofilms. The management of chronic wound infection is limited by the complexity of selecting an appropriate antimicrobial dressing with antibiofilm activity due to antimicrobial resistance in biofilms. Herein, the in situ developed bacterial cellulose/poly(vinyl alcohol) (BC-PVA) composite is ex situ modified with genipin-crosslinked silk sericin (SS) and azithromycin (AZM) (SSga). The composite is evaluated as a wound dressing material for preventing the development, dispersion, and/or eradication of microbial biofilm. Fourier transform infrared spectroscopy confirms the intermolecular interactions between the components of BC-PVA@SSga scaffolds. The addition of PVA during BC production significantly increases the porosity from 53.5% ± 2.3% to 83.5% ± 2.9%, the pore size from 2.3 ± 1.9 to 16.8 ± 4.5 µm, the fiber diameter from 35.5 ± 10 to 120 ± 27.4 nm, and improves the thermal stability and flexibility. Studies using bacteria and fungi indicate high inhibition and disruption of biofilms upon AZM addition. In vitro biocompatibility analysis confirms the nontoxic nature of BC-PVA@SSga toward HaCaT and NIH3T3 cells, whereas the addition of SS enhances cell proliferation. The developed BC-PVA@SSga accelerates wound healing in the infected mouse model, thus can be a promising wound dressing biomaterial.

Biodegradable, Super-Strong, and Conductive Cellulose Macrofibers for Fabric-Based Triboelectric Nanogenerator.

Electronic fibers used to fabricate wearable triboelectric nanogenerator (TENG) for harvesting human mechanical energy have been extensively explored. However, little attention is paid to their mutual advantages of environmental friendliness, mechanical properties, and stability. Here, we report a super-strong, biodegradable, and washable cellulose-based conductive macrofibers, which is prepared by wet-stretching and wet-twisting bacterial cellulose hydrogel incorporated with carbon nanotubes and polypyrrole. The cellulose-based conductive macrofibers possess high tensile strength of 449 MPa (able to lift 2 kg weights), good electrical conductivity (~ 5.32 S cm-1), and excellent stability (Tensile strength and conductivity only decrease by 6.7% and 8.1% after immersing in water for 1 day). The degradation experiment demonstrates macrofibers can be degraded within 108 h in the cellulase solution. The designed fabric-based TENG from the cellulose-base conductive macrofibers shows a maximum open-circuit voltage of 170 V, short-circuit current of 0.8 µA, and output power at 352 µW, which is capable of powering the commercial electronics by charging the capacitors. More importantly, the fabric-based TENGs can be attached to the human body and work as self-powered sensors to effectively monitor human motions. This study suggests the potential of biodegradable, super-strong, and washable conductive cellulose-based fiber for designing eco-friendly fabric-based TENG for energy harvesting and biomechanical monitoring.

A Biodegradable and Recyclable Piezoelectric Sensor Based on a Molecular Ferroelectric Embedded in a Bacterial Cellulose Hydrogel.

Currently, various electronic devices make our life more and more safe, healthy, and comfortable, but at the same time, they produce a large amount of nondegradable and nonrecyclable electronic waste that threatens our environment. In this work, we explore an environmentally friendly and flexible mechanical sensor that is biodegradable and recyclable. The sensor consists of a bacterial cellulose (BC) hydrogel as the matrix and imidazolium perchlorate (ImClO4) molecular ferroelectric as the functional element, the hybrid of which possesses a high sensitivity of 4 mV kPa-1 and a wide operational range from 0.2 to 31.25 kPa, outperforming those of most devices based on conventional functional biomaterials. Moreover, the BC hydrogel can be fully degraded into glucose and oligosaccharides, while ImClO4 can be recyclable and reused for the same devices, leaving no environmentally hazardous electronic waste.

Pressure-induced structure, elasticity, intrinsic hardness and ideal strength of tetragonal C4N.

A tetragonal C4N (t-C4N) structure was predicted via CALYPSO code, and the effects of pressure on its structural and mechanical properties were studied. The results show that t-C4N is different from various 2D CxNy compounds with a new type 3D crystal structure, which is similar to diamond. Bulk t-C4N is equipped with excellent elastic properties. When the pressure is increased from 0 GPa to 350 GPa, its bulk modulus B, shear modulus G and Young's modulus E are increased from 426.9 GPa to 1123.1 GPa, 371.4 GPa to 582.9 GPa and 863.7 GPa to 1490.9 GPa, respectively. The anisotropic Bmax, Gmax and Emax are increased from 582.38 GPa to 1751.41 GPa, 478.29 GPa to 1033.97 GPa and 1281.26 GPa to 2490.14 GPa, respectively. When the pressure is 0 GPa, the hardness calculated by Chen's and Tian's models are 51.15 GPa and 51.81 GPa, respectively. Its ideal tensile strength in [111] orientation is the smallest (63.46 GPa), which indicates that the (111) planes allow easy cleavage. The smallest ideal shear strength (67.98 GPa) can be obtained in the (111)[11̄0] orientation, which suggests its theoretical hardness is about 67.98 GPa. Due to its excellent mechanical properties, t-C4N can be used as an industrial superhard material.

Programmable Anisotropic Hydrogel Composites for Soft Bioelectronics.

Fabrication of hydrogel composites embedded with aligned 1D nanoparticles has shown substantial growth over the past 5 years. Direct ink printing technology (DIW) has been used in this work to create the alignment of the 1D nanoparticles due to the shear gradient of the pseudoplastic precursor (2-hydroxyethyl methacrylate (HEMA) with thickening agents). Orderly distributed 1D particles constructing anisotropic nanostructures endow the hydrogel composite with unique mechanical, electric, or electromechanical coupling properties. Quasi-static uniaxial tensile test, electric resistivity, and piezoresistivity measurements have been conducted for investigating the mechanical, electric, and electromechanical coupling properties of the hydrogel composites, respectively. Based on the experimental results, it can be speculated that the developed printing process is able to fabricate hydrogel composites with programmable anisotropic mechanical, electric, and electromechanical properties. The products pumped out from this work have the potential of being substrates for soft devices and may have a great impact on the fields of flexible bioelectronics.

Hierarchical-structured bacterial cellulose/potato starch tubes as potential small-diameter vascular grafts.

To achieve long-term patent small-diameter (<6 mm) vascular implants, biomimetic vascular grafts have gained much attention in promoting in situ blood vessel regeneration. In this study, hierarchical-structured bacterial cellulose/potato starch (BC/PS) composites were biosynthesized by the addition of swollen PS. Investigations on the physicochemical properties of BC/PS composites showed that the properties could be improved and tailored by the addition of swollen PS. The composites displayed a morphology, water content, thermal properties, mechanical properties, and biocompatibility appropriate for vascular tissue engineering. Most importantly, the BC/PS grafts, with a dense inner surface and a circumferential macroporous outer layer, possessed 75% patency and promoted rapid blood vessel regeneration in in vivo assessment on rabbits, with complete endothelium monolayer, organized smooth muscle cells, rich new capillaries, and deposited extracellular matrix. Collectively, these findings demonstrate that hierarchical-structured BC/PS tubes hold great promise as artificial small-diameter vascular grafts.

Immune Response to Silk Sericin-Fibroin Composites: Potential Immunogenic Elements and Alternatives for Immunomodulation.

The unique properties of silk proteins (SPs), particularly silk sericin (SS) and silk fibroin (SF), have attracted attention in the design of scaffolds for tissue engineering over the past decades. Since SF has good mechanical properties, while SS displays bioactivity, scaffolds combining both proteins should exhibit complementary properties enhancing the potential of these materials. Unfortunately, SS-SF composites can generate chronic immune responses and their immunogenic element is not completely clear. The potential of SS-SF composites in tissue engineering, elements which may contribute to their immunogenicity, and alternatives for their preparation and design, to modulate the immune response and take advantage of their useful properties, are discussed in this review. It is known that SS can enhance ß-sheet formation in SF, which may act as hydrophobic regions with a strong affinity for adsorption proteins inducing the chronic recruitment of inflammatory cells. Therefore, tailoring the exposure of hydrophobic regions at the scaffold surface should represent a viable strategy to modulate the immune response. This can be achieved by coating SS-SF composites with SS or other hydrophilic polymers, to take advantage of their antibiofouling properties. Research is still needed to realize the full potential of these composites for tissue engineering.

Nanofibrous tissue engineering scaffold with nonlinear elasticity created by controlled curvature and porosity.

Micro-crimped fibers have been widely used in the field of tissue repair to mimic the natural tissue structure and mechanical properties. However, the electrospun nanofibrous membrane is a kind of dense structure, which cannot meet the requirements of mechanical properties and permeability. In this study, we prepared nanofibrous scaffold with controllable porosity and crimpness by sacrificing fiber components and releasing residual stress. The results show that the crimpness of the fiber is positively related to the porosity, and with the increase of porosity, the fiber crimpness increases greatly. Meanwhile, the scaffold modulus was reduced by 86% and the elongation at break doubled, which is similar to natural blood vessels. Moreover, it is found that the porous micro-crimped fiber scaffold promotes the adhesion and diffusion of endothelial cells, and facilitates the rapid endothelialization of the scaffold, which has a great potential for practical application.

Bacterial cellulose-based composites for biomedical and cosmetic applications: Research progress and existing products.

Bacterial cellulose (BC) is a promising unique material for various biomedical and cosmetic applications due to its morphology, mechanical strength, high purity, high water uptake, non-toxicity, chemical controllability, and biocompatibility. Today, extensive investigation is into the manufacturing of BC-based composites with other components such as nanoparticles, synthetic polymers, natural polymers, carbon materials, and biomolecules, which will allow the development of a wide range of biomedical and cosmetic products. Moreover, the addition of different reinforcement substances into BC and the organized arrangement of BC nano-fibers have proven a promising improvement in their properties for biomedical applications. This review paper highlights the progress in synthesizing BC-based composites and their applications in biomedical fields, such as wound healing, drug delivery, tissue engineering, and cancer treatment. It emphasizes high-performance BC-based materials and cosmetic applications. Furthermore, it presents challenges yet to be defeated and future possibilities for BC-based composites for biomedical and cosmetic applications.

In Situ Synthesized Selenium Nanoparticles-Decorated Bacterial Cellulose/Gelatin Hydrogel with Enhanced Antibacterial, Antioxidant, and Anti-Inflammatory Capabilities for Facilitating Skin Wound Healing.

Bacterial-associated wound infection and antibiotic resistance have posed a major burden on patients and health care systems. Thus, developing a novel multifunctional antibiotic-free wound dressing that cannot only effectively prevent wound infection, but also facilitate wound healing is urgently desired. Herein, a series of multifunctional nanocomposite hydrogels with remarkable antibacterial, antioxidant, and anti-inflammatory capabilities, based on bacterial cellulose (BC), gelatin (Gel), and selenium nanoparticles (SeNPs), are constructed for wound healing application. The BC/Gel/SeNPs nanocomposite hydrogels exhibit excellent mechanical properties, good swelling ability, flexibility and biodegradability, and favorable biocompatibility, as well as slow and sustainable release profiles of SeNPs. The decoration of SeNPs endows the hydrogels with superior antioxidant and anti-inflammatory capability, and outstanding antibacterial activity against both common bacteria (E. coli and S. aureus) and their multidrug-resistant counterparts. Furthermore, the BC/Gel/SeNPs hydrogels show an excellent skin wound healing performance in a rat full-thickness defect model, as evidenced by the significantly reduced inflammation, and the notably enhanced wound closure, granulation tissue formation, collagen deposition, angiogenesis, and fibroblast activation and differentiation. This study suggests that the developed multifunctional BC/Gel/SeNPs nanocomposite hydrogel holds a great promise as a wound dressing for preventing wound infection and accelerating skin regeneration in clinic.