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Purpose: To describe the effects of melatonin associated with bacterial cellulose-based hydrogel on healing of skin wounds in diabetic rats., Methods: Streptozotocin was used to induce diabetes in Wistar rats. After wound induction, animals were randomly divided into groups GC, GDCC, GDCB, and GDMCB. Animals were evaluated in days 3, 7, and 14 for the following variables: glycemic levels, histopathological and histochemical analyses, healing rate, morphometry and C-reactive protein., Results: There was no change in glycemic levels in the diabetic animals as a result of the treatments; histopathological analyses showed better healing in GDCB and GDMCB groups, as well as histochemistry; at day 14, the highest healing rate was observed in animals from the GDMCB group, reaching almost 100%; morphometry revealed a significant increase of fibroblasts and reduction of macrophages and blood vessels in lesions treated with bacterial cellulose associated or not with melatonin when compared to the other experimental groups. There was also an increase in C-reactive protein in GDCC group at day 14., Conclusion: Bacterial cellulose-based dressings associated with systemic melatonin showed beneficial results in experimentally induced wounds in diabetic rats, favoring the healing process.

Purpose: Bacterial cellulose (BC) has shown high capacity for the treatment of wounds and burns, providing a moisty environment. Calcium alginate can be associated with BC to create gels that aid in wound debridement and contribute to appropriate wound healing. This study is aimed at characterizing and evaluating the use of bacterial cellulose/alginate gel in skin burns in rats., Methods: Cellulose and cellulose/alginate gels were compared regarding the capacity of liquid absorption, moisture, viscosity, and potential cytotoxicity. The 2nd degree burns were produced using an aluminum metal plate (2.0cm) at 120ºC for 20s on the back of rats. The animals were divided into non-treated, CMC(Carboxymethylcellulose), Cellulose(CMC with bacterial cellulose), and Cellulose/alginate(CMC with bacterial cellulose and alginate). The animals received topical treatment 3 times/week. Biochemical (MPO, NAG and oxidative stress), histomorphometry and immunohistochemical assays (IL-1β IL-10 and VEGF) were conducted on the 14th, 21st, 28th, and 35th days., Results: Cellulose/Alginate gel showed higher absorption capacity and viscosity compared to Cellulose gel, with no cytotoxic effects. Cellulose/alginate presented lower MPO values, a higher percentage of IL-10, with greater and balanced oxidative stress profile., Conclusions: The use of cellulose/alginate gel reduced neutrophils and macrophage activation and showed greater anti-inflammatory response, which can contribute to healing chronic wounds and burns.

Purpose: To evaluate using a biocellulose-based hydrogel as an adjuvant in the healing process of arterial ulcers., Methods: A prospective single group quasi-experimental study was carried out with chronic lower limb arterial ulcer patients. These patients received biocellulose-based hydrogel dressings and outpatient guidance on dressing and periodic reassessments. The primary outcomes were the ulcer-healing rate and product safety, which were assessed by ulcer area measured in photographic records of pre-treatment and posttreatment after 7, 30, and 60 days. Secondary outcomes were related to clinical assessment by the quality-of-life scores (SF-36 and EQ-5D) and pain, evaluated by the visual analogue scale (VAS)., Results: Seventeen participants were included, and one of them was excluded. Six patients (37%) had complete wound healing, and all patients had a significant reduction in the ulcer area during follow-up (233.6mm2 versus 2.7mm2) and reduction on the score PUSH 3.0 (p < 0.0001). The analysis of the SF-36 and EQ-5D questionnaires showed a statistically significant improvement in almost all parameters analyzed and with a reduction of pain assessed by the VAS., Conclusions: The biocellulose-based hydrogel was safe and showed a good perspective to promoting the necessary conditions to facilitate partial or complete healing of chronic arterial ulcers within a 60-day follow-up. Quality of life and pain were positively affected by the treatment.

Ocular disorders, encompassing both common ailments like dry eye syndrome and more severe situations for instance age-related macular degeneration, present significant challenges to effective treatment due to the intricate architecture and physiological barriers of the eye. Polysaccharides are emerging as potential solutions for drug delivery to the eyes due to their compatibility with living organisms, natural biodegradability, and adhesive properties. In this review, we explore not only the recent advancements in polysaccharide-based technologies and their transformative potential in treating ocular illnesses, offering renewed optimism for both patients and professionals but also anatomy of the eye and the significant obstacles hindering drug transportation, followed by an investigation into various drug administration methods and their ability to overcome ocular-specific challenges. Our focus lies on biological adhesive polymers, including chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer, known for their adhesive characteristics enhancing drug retention on ocular surfaces and increasing bioavailability. A detailed analysis of material designs used in ophthalmic formulations, such as gels, lenses, eye drops, nanofibers, microneedles, microspheres, and nanoparticles, their advantages and limitations, the potential of formulations in improving therapeutic outcomes for various eye conditions. Moreover, we underscore the discovery of novel polysaccharides and their potential uses in ocular drug delivery., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Burn wound regeneration is a complex process, which has many serious challenges such as slow wound healing, secondary infection, and inflammation. Therefore, it is essential to utilise appropriate biomaterials to accelerate and guide the wound healing process. Bacterial cellulose (BC), a natural polymer synthesised by some bacteria, has attracted much attention for wound healing applications due to its unique properties including excellent physicochemical and mechanical properties, simple purification process, three-dimensional (3D) network structure similar to extracellular matrix, high purity, high water holding capacity and significant permeability to gas and liquid. BC's lack of antibacterial activity significantly limits its biomedical and tissue engineering application, but adding antimicrobial agents to it remarkably improves its performance in tissue regeneration applications. Burn wound healing is a complex long-lasting process. Using biomaterials in wound treatment has shown that they can satisfactorily accelerate wound healing. The purpose of this review is to elaborate on the importance of BC-based structures as one of the most widely used modern wound dressings in the treatment of burn wounds. In addition, the combination of various drugs, agents, cells and biomolecules with BC to expand its application in burn injury regeneration is discussed. Finally, the main challenges and future development direction of BC-based structures for burn wound repair are considered. The four most popular search engines PubMed/MEDLINE, Science Direct, Scopus and Google Scholar were used to help us find relevant papers. The most frequently used keywords were bacterial cellulose, BC-based biocomposite, wound healing, burn wound and vascular graft., (© 2024 The Wound Healing Society.)

Eschar dermabrasion is an easy, cost-effective and dependable technique for debriding deep partial-thickness burn wounds, highly suitable for paediatric scalds. Postoperative dressing plays a crucial role in the subsequent healing process. While allogenic skin (AGS) has long been considered as the optimal coverage for abraded burn wounds by Chinese burn specialists, its clinical application on children has encountered challenges. In recent years, our department has observed promising results in the application of bacterial cellulose dressing on paediatric burn wounds after dermabrasion surgery. This study aimed to retrospectively review qualified cases from the past 5 years and categorize them into two groups: 201 cases in the AGS group and 116 cases in the bacterial cellulose dressing (BCD) group. Upon statistical analysis, no differences were oberved between the groups in terms of demographic information and wound characteristics. However, the BCD group had a significantly longer surgery time (44.3 ± 7.0 min vs. 31.5 ± 6.1 min, p < 0.01) and shorter healing time (19.6 ± 2.2 days vs. 24.4 ± 4.3 days, p < 0.01) compared to the AGS group. Moreover, the BCD group required fewer dressing changes (3.5 ± 0.8 vs. 6.7 ± 2.1, p < 0.01) and demonstrated lower rates of skin grafting (10/116 vs. 46/201, p = 0.036). In conclusion, our findings suggest that the bacterial cellulose material may serve as an optimal coverage option for paediatric abraded scald wounds., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Bacterial keratitis is one of the vision-threatening ocular diseases that is increasing at an alarming rate due to antimicrobial resistance. One of the primary causes of antimicrobial resistance could be biofilm formation, which alters the mechanism and physiology of the microorganisms. Even a potent drug fails to inhibit biofilm due to the extracellular polysaccharide matrix surrounding the bacteria, inhibiting the permeation of drugs. Therefore, we aimed to develop carboxylated nanocellulose fibers loaded with moxifloxacin (Mox-cNFC) as a novel drug delivery system to treat bacterial corneal infection. Nanocellulose fibers were fabricated using a two-step method involving citric acid hydrolysis followed by TEMPO oxidation to introduce carboxylated groups (1.12 mmol/g). The Mox-cNFC particles showed controlled drug release till 40 h through diffusion. In vitro biofilm inhibition studies showed the particle's ability to disrupt the biofilm matrix and enhance the drug penetration to achieve optimal concentrations that inhibit the persister cells (without increasing minimum inhibitory concentration), thereby reducing the bacterial drug-resistant property. In vivo studies revealed the therapeutic potential of Mox-cNFC to treat Staphylococcus aureus-induced bacterial keratitis with once-a-day treatment, unlike neat moxifloxacin. Mox-cNFC could improve patient compliance by reducing the frequency of instillation and a controlled drug release to prevent toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purposes: Postoperative bleeding remains a life-threatening complication in thyroid surgery. The aim was to assess the efficacy of four different hemostatic agents, Collagen-Fibrinogen-Thrombin Patch (CFTP) in two sizes (3 × 2.5 cm and 9.5 × 4.8 cm), polysaccharide particles (1 g) and Cellulose Gauze (2.5 × 5 cm) on postoperative drainage volume (DV) compared to a control group., Methods: We included from October 2007 until Mai 2011, 150 patients (30 per group) for this monocentric, retrospective case-controlled study. Patients were scheduled for a hemithyroidectomy or thyroidectomy. The primary endpoint was the postoperative DV within the first 24 h, secondary the incidence of adverse events., Results: There were no difference in demographic parameters. The mean DV (± SD) was 51.15 (± 36.86) ml in the control, 50.65 (± 42.79) ml in small (3 × 2.5 cm), 25.38 (± 23.99) ml in large CFTP (9.5 × 4.8 cm), 53.11 (± 39.48) ml in the polysaccharide particles and 48.94 (± 30.59) ml in the cellulose gauze group. DV was significantly reduced with the large CFTP (p < 0.05) compared to all other groups. There were no adverse events., Conclusions: We were able to demonstrate a significant reduction in the DV for the large CFTP group compared to the other collectives. Although this as being associated with not inconsiderable costs and we would only recommend its use for high-risk patients only., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Diabetic foot ulcers (DFUs) are a crucial complication of diabetes, as in a diabetic wound, each step of the physiological healing process is affected. This entails a more easily infectable wound, and delayed tissue regeneration due to the inflammation that occurs, leading to a drastic decrease in the overall patient's quality of life. As a strategy to manage DFUs, skin alternatives and wound dressings are currently receiving a lot of attention as they keep the wound environment "under control", while providing bioactive compounds that help to manage infection and inflammation and promote tissue repair. This has been made possible thanks to the advent of emerging technologies such as 3D Bioprinting to produce skin resembling constructs or microfluidics (MFs) that allows the manufacture of nanoparticles (NPs) that act as drug carriers, in a prompt and less expensive way. In the present proof-of-concept study, the possibility of combining two novel and appealing techniques in the manufacturing of wound dressings has been demonstrated for first time. The novelty of this work consists in the combination of liposomes (LPs) encapsulating the active pharmaceutical ingredient (API) into a hydrogel that is further printed into a three-dimensional scaffold for wound dressing; to the knowledge of the authors this has never been done before. A grid-shaped scaffold has been produced through the coaxial 3D bioprinting technique which has allowed to combine, in one single filament, two different bioinks. The inner core of the filament is a nanocomposite hydrogel consisting of hydroxyethyl cellulose (HEC) and PEGylated LPs encapsulated with thyme oil (TO) manufactured via MFs for the first time. The outer shell of the filament, instead, is represented by a hybrid hydrogel composed of sodium alginate/cellulose nanocrystals (SA/CNC) and enriched with free TO. This provides a combination of two different release ratios of the API, a bulk release for the first 24 h thanks to the free TO in the shell of the filament and a sustained release for up to 10 days provided from the API inside the LPs. Confocal Microscopy verified the actual presence of the LPs inside the scaffold after printing and evaluation using the zone of inhibition test proved the antibacterial activity of the manufactured scaffolds against both Gram-positive and Gram-negative bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Uncontrolled hemorrhage is still the most common cause of potentially preventable death after trauma in prehospital settings. However, there rarely are hemostatic materials that can achieve safely and efficiently rapid hemostasis simultaneously. Here, new carbonized cellulose-based aerogel hemostatic material is developed for the management of noncompressible torso hemorrhage, the most intractable issue of uncontrolled hemorrhage. The carbonized cellulose aerogel is derived from the Agaricus bisporus after a series of processing, including cutting, carbonization, purification, and freeze-drying. In vitro, the carbonized cellulose aerogels with porous structure show improved hydrophilicity, good blood absorption, and coagulation ability, rapid shape recoverable ability under wet conditions. And in vivo, the carbonized aerogels show effective hemostatic ability in both small and big animal serious hemorrhage models. The amount of blood loss and the hemostatic time of carbonized aerogels are all better than the positive control group. Moreover, the mechanism studies reveal that the good hemostatic ability of the carbonized cellulose aerogel is associated with high hemoglobin binding efficiency, red blood cell absorption, and platelets absorption and activation. Together, the carbonized aerogel developed in this study could be promising for the management of uncontrolled hemorrhage., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Pressure ulcers are soft-tissue damage associated with tissue exposure to sustained deformations and stress concentrations. In patients who are proned for ventilation or surgery, such damage may occur in the superficial chest tissues that are compressed between the rib cage and the support surface. Prophylactic dressings have been previously proven as generally effective for pressure ulcer prevention. In this study, our goal was to develop a novel computational modelling framework to investigate the biomechanical efficacy of a dressing with a soft cellulose fluff core in protecting proned surgical patients from chest pressure ulcers occurring on the operating table, due to body fixation by the Relton-Hall frame. We compared the levels of mechanical compressive stresses developing in the soft chest tissues, above the sternum and ribs, due to the trunk weight, whilst the body is supported by the Relton-Hall frame pads, with versus without the prophylactically applied bilateral dressings. The protective efficacy index for the extremely high stresses, above the 95th-percentile, were 40.5%, 25.6% and 24.2% for skin, adipose and muscle, respectively, indicating that the dressings dispersed elevated soft-tissue stresses. The current results provide additional support for using soft cellulose fluff core dressings for pressure ulcer prophylaxis, including during surgery., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Constipation can seriously affect the quality of life and increase the risk of colorectal cancer. The present strategies for constipation therapy have adverse effects, such as causing irreversible intestinal damage and affecting the absorption of nutrients. Nanocrystalline cellulose (NCC), which is from natural plants, has good biocompatibility and high safety. Herein, we used NCC to treat constipation assessed by the black stool, intestinal tissue sections, and serum biomarkers. We studied the effect of NCC on gut microbiota and discussed the correlation of gut microbiota and metabolites. We evaluated the long-term biosafety of NCC. NCC could effectively treat constipation through gut microbiota metabolism, which required a small dosage and did not affect the organs and intestines. NCC could be used as an alternative to medications and dietary fiber for constipation therapy.

Unfortunately hemorrhage and its complications (e.g. anemia, organ failure, and hypothermia) induced by traumatic injury, surgery, and disorders of bleeding play an all too familiar role in human morbidity and mortality. Therefore, it is difficult to overstate the importance of better understanding the role of polysaccharides in advanced hemostatic dressings (HDs). This review includes consideration of polysaccharide hemostatic dressing mechanism of action, relative efficacy, cost and safety. Polysaccharide-based HDs are widely used in management not only of external and internal bleeding but also of massive hemorrhage. These polysaccharide-based HDs have been shown to be effective in both compressible and non-compressible hemorrhage. Hemostatic dressings are designed with different principles depending on location and extent of injury. This review focuses on polysaccharide HD design and associated hemostatic mechanisms. It addresses current issues, challenges, and future perspectives., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chronic ulcers are among the main causes of morbidity and mortality due to the high probability of infection and sepsis and therefore exert a significant impact on public health resources. Numerous types of dressings are used for the treatment of skin ulcers-each with different advantages and disadvantages. Bacterial cellulose (BC) has received enormous interest in the cosmetic, pharmaceutical, and medical fields due to its biological, physical, and mechanical characteristics, which enable the creation of polymer composites and blends with broad applications. In the medical field, BC was at first used in wound dressings, tissue regeneration, and artificial blood vessels. This material is suitable for treating various skin diseases due its considerable fluid retention and medication loading properties. BC membranes are used as a temporary dressing for skin treatments due to their excellent fit to the body, reduction in pain, and acceleration of epithelial regeneration. BC-based composites and blends have been evaluated and synthesized both in vitro and in vivo to create an ideal microenvironment for wound healing. This review describes different methods of producing and handling BC for use in the medical field and highlights the qualities of BC in detail with emphasis on biomedical reports that demonstrate its utility. Moreover, it gives an account of biomedical applications, especially for tissue engineering and wound dressing materials reported until date. This review also includes patents of BC applied as a wound dressing material.

Aim: The aim was to compare two dressing treatments for partial-thickness burns: biosynthetic cellulose dressing (BsC) (Epiprotect® S2Medical AB, Linköping, Sweden) and porcine xenograft (EZ Derm®, Mölnlycke Health Care, Gothenburg, Sweden)., Methods: Twenty-four adults with partial-thickness burns were included in this randomized clinical trial conducted at The Burn Centers in Linköping and Uppsala, Sweden between June 2016 and November 2018. Time to healing was the primary outcome. Secondary outcomes were wound infection, pain, impact on everyday life, length of hospital stay, cost, and burn scar outcome (evaluated with POSAS)., Results: We found no significant differences between the two dressing groups regarding time to healing, wound infection, pain, impact on everyday life, duration of hospital stay, cost, or burn scar outcome at the first follow up. Burn scar outcome at the 12-month follow up showed that the porcine xenograft group patients scored their scars higher on the POSAS items thickness (p = 0.048) and relief (p = 0.050). This difference was, however, not confirmed by the observer., Conclusions: The results showed the dressings performed similarly when used in adults with burns evaluated as partial thickness., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gastric ulcer (GU) is the most common and chronic inflammatory condition mediated by multiple immune cells like neutrophils, macrophages, and lymphocytes with multiple pro-inflammatory cytokine interleukins such as IL-8, IL-10, IL-β, and interferon-γ (IFN-γ). Copper (Cu) is one of the essential micronutrients mainly found in the liver and brain. It plays a major role in metabolism, enzyme conversion, free radical scavenging, trafficking agents, and many others. Due to its various roles in the biological system, it can also be used as a therapeutic agent in many diseases like colon cancer, bone fracture healing, angiogenesis, as an antibacterial, wound-healing and radiotherapeutic agents. In this study, we used thiol-functionalized cellulose-conjugated copper-oxide nanoparticles (Cu I/II O NPs) synthesized under environmentally friendly conditions. We have evaluated the effects of cellulose-conjugated Cu I/II O NPs against ethanol-induced gastric ulcer in Wistar rats. The cellulose-conjugated Cu I/II O NPs were evaluated against different physical, histochemical, and inflammatory parameters. The NPs promoted mucosal healing by ameliorating ulcerative damage, restoring the histoarchitecture of gastric mucosa, and inhibiting pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and other inflammatory biomarkers such as myeloperoxidase (MPO) activity and nitric oxide (NO) levels. The current study's findings suggest that cellulose-conjugated Cu I/II O NPs exerted antiulcer effects on the preclinical rat model and have promising potential as a novel therapeutic agent for the treatment of gastric ulcers.

Radioisotope therapy (RIT) of cancer is restrained by the nonspecific distribution of radioisotope and ineptitude for metastatic tumors. Meanwhile, the clinical application of immune checkpoint blockade (ICB) confronts problems such as low responsive rate, multiple administration requirements and immune-related adverse events (irAE). To address these challenges, we prepared an injectable suspension by immobilizing 131 I-labeled anti-programmed cell death-ligand 1 antibody (αPD-L1) in bacterial cellulose for precise and durable radio-immunotherapy of cancer. The crisscross network structure of bacterial cellulose nanofibers would contribute to the long-term retention of 131 I-labeled αPD-L1 within tumors, which could reduce the side effect stemmed from the nonspecific 131 I distribution in normal tissues. The potent long-term RIT of 131 I, combined with ICB by αPD-L1, could effectively restrain the growth of primary tumor in mice. In addition to the direct killing effect, 131 I-αPD-L1 immobilized by bacterial cellulose could enhance the immunogenic cell death (ICD) of cancer cells, activating the maturation of multiple immune cells to induce a systemic anti-tumor immune effect. Our therapeutic strategy could suppress spontaneous cancer metastasis and prolong the survival time of tumor-bearing mice. This study proposed a new approach for combined radio-immunotherapy and a novel solution for tumor metastasis in advanced-stage cancers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Resistant starch 2 (RS2) may offer therapeutic value to irritable bowel syndrome (IBS) patients particularly in combination with minimally fermented fibre, but tolerability data are lacking. The present study evaluated the tolerability of RS2, sugarcane bagasse and their combination in IBS patients and healthy controls. Following baseline, participants consumed the fibres in escalating doses lasting 3 d each: RS2 (10, 15 and 20 g/d); sugarcane bagasse (5, 10 and 15 g/d); and their combination (20, 25 and 30 g/d). Gastrointestinal symptoms were assessed daily. Six IBS patients and five controls were recruited. No differences in overall symptoms from baseline were found across the fibre doses (IBS, P = 0⋅586; controls, P = 0⋅687). For IBS patients, all RS2 doses led to increased bloating. One IBS patient did not tolerate the low combination dose and another the high sugarcane bagasse dose. Supplementation of RS2 ≤ 20 g/d caused mild symptoms and was generally tolerated in IBS patients even when combined with minimally fermented fibre., (© The Author(s) 2022.)

The treatment of cutaneous leishmaniasis (CL) in Brazil using pentavalent antimony (Sb v ) is associated with a high failure rate and long time to heal. Moreover, standard Sb v treatment cures only 50-60% of the cases. In this pilot clinical trial, we evaluated the topical use of bacterial cellulose (BC) bio-curatives + Sb v in the treatment of CL caused by L. braziliensis, in Bahia, Brazil. A total of 20 patients were randomized in two groups assigned to receive either parenteral Sb v alone or parenteral Sb v plus topically applied BC bio-curatives. CL patients treated with Sb v  + topical BC bio-curatives had a significantly higher cure rate at 60 days post initiation of treatment compared to CL patients treated with Sb v alone (P=0.01). At day 90 post initiation of treatment, cure rate was similar in the two groups as was overall healing time. Adverse effects or local reactions to topical BC application were not observed. This pilot trial shows that the potential use of a combined therapy consisting of topical BC bio-curatives and parenteral Sb v in favoring healing of CL lesions caused by L. braziliensis, at an early time point., (Copyright © 2021. Published by Elsevier B.V.)

The main objective of this study was to investigate the effects of bacterial cellulose hydrogel (BCH) incorporated into montmorillonite (MMT) and its underlying mechanisms of action on a skin wound healing mouse model following pressure injury model. Komagataeibacter hansenii was used to obtain 5 cm in diameter and 0.8 mm of thickness circular bacterial cellulose (BC) sheets, which were incorporated with MMT by deposition ex-site using a 0.1% MMT suspension (100 rpm for 24 h at 28 °C). Afterward, Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM) were used to characterize the bacterial cellulose hydrogel incorporated into montmorillonite (BCH-MMT). The pressure injury model was assessed by macroscopic and histological analysis in male Swiss mice. Both, BC and BCH-MMT, showed a typical FTIR spectrum of cellulosic substrates with pronounces bands around 3344, 2920, 1637, and 1041 cm -1 while microparticles of MMT dispersed uniformly throughout BC were revealed by SEM photographs. Animals treated with BCH-MMT showed significant healing of pressure ulcers as demonstrated by reduced area of redness and spontaneous hyperalgesia, lower amounts of in-site inflammatory cells (to the same level as the positive control Dersani®) and ultimately, complete epidermis re-epithelialization and tissue regeneration. Altogether, these findings suggest that a modified BCH-MMT film could serve as scaffolding for skin tissue engineering and potentially as a novel dressing material for pressure injury., (Copyright © 2021. Published by Elsevier B.V.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Significance: Wound dressings are frequently used for wound covering and healing. Ideal wound dressings should provide a moist environment for wounds and actively promote wound healing and skin recovery. The materials used as ideal wound dressings should possess specific properties, thus accelerating skin tissue regeneration process. Recent Advances: Bacterial cellulose (BC) is a natural polymer synthesized by some bacteria. As a kind of natural biopolymer, BC shows good biological activity, biodegradability, and biological adaptability. It has many unique physical, chemical, and biological properties, such as ultrafine nanofiber network, high crystallinity, high water absorption and retention capacity, and high tensile strength and elastic modulus. These excellent properties of BC have laid the foundation for its application as dressing in wound healing. Critical Issues: To optimize the biocompatibility and antimicrobial activity of BC, different methods including microbial fermentation, physical modification, chemical modification, and compound modification have been adopted to modify BC to ensure a better application in wound healing. BC-based wound dressings have been applied in infected wounds, acute traumatic injuries, burns, and diabetic wounds, showing remarkable therapeutic effects on promoting wound healing. Furthermore, there have been some commercial BC-based dressings and they have been utilized in clinical practice. Future Directions: Because of its excellent physicochemical characteristics and biological properties, BC shows high clinical value to be used as a wound dressing for skin tissue regeneration.

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and β-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.

It is difficult to retain tumoricidal doses of ethanol in large or unencapsulated tumours without causing intoxication or damaging surrounding tissue. Ethyl cellulose-ethanol ablation (ECEA) overcomes this limitation by trapping ethanol intratumorally. To evaluate the safety of ECEA and to develop a clinically feasible workflow, a single-arm pilot study was performed in cats with lingual/sublingual squamous cell carcinoma (SCC). Six cats underwent intratumoral injection of 6% ethyl cellulose in ethanol. Subjects were observed overnight. There was mild bleeding and transient hyperthermia, and injection site pain and swelling that improved with anti-inflammatory drugs. Serum ethanol was minimally elevated; the mean concentration peaked 1 hour after injection (129 +/- 15.1 nM). Cats were rechecked at weeks 1 and 2; booster treatments were given in cats (n = 3) with stable quality of life and partial response to therapy. Recheck examinations were then performed monthly. The longest tumour dimension increased in each animal (progressive disease via cRECIST); however, estimated tumour volume was reduced in 3 of 6 cats, within 1 week of ECEA. All cats were euthanized (median survival time 70 days) because of local tumour progression and/or lingual dysfunction that was likely hastened by ECEA. ECEA is not a viable treatment for feline lingual/sublingual SCC; tumour volume was effectively reduced in some cats, but the simultaneous loss of lingual function was poorly tolerated. Further optimization may make ECEA a useful option for SCC at other oral sites in the cat, and for head and neck malignancies in other species., (© 2021 John Wiley & Sons Ltd.)

Antibiotic abuse resulted in the emergence of multidrug-resistant Gram-positive pathogens, which pose a severe threat to public health. It is urgent to develop antibiotic substitutes to kill multidrug-resistant Gram-positive pathogens effectively. Herein, the antibacterial dialdehyde nanocrystalline cellulose (DNC) was prepared and characterized. The antibacterial activity and biosafety of DNC were studied. With the increasing content of aldehyde groups, DNC exhibited high antibacterial activity against Gram-positive pathogens in vitro. DNC3 significantly reduced the amounts of methicillin-resistant Staphylococcus aureus (MRSA) on the skin of infected mice models, which showed low cytotoxicity, excellent skin compatibility, and no acute oral toxicity. DNC exhibited potentials as antibiotic substitutes to fight against multidrug-resistant bacteria, such as ingredients in salves to treat skin infection and other on-skin applications.

The usage of materials with the potential to accelerate wound healing is a great benefit for patients and health care systems. This study evaluated the impact of using graphene oxide (GO)-cellulose nanocomposite on skin wound healing via in vitro and in vivo investigations. The nanomaterial was synthesized and characterized. Cytocompatibility performance of the GO-cellulose was investigated through in vitro testing based on MTT and live/dead assays by EA.hy926 human endothelial cells (ECs). Additionally, the effect of GO-cellulose on induced wound scratch model using EA.hy926 ECs was investigated. Finally, the therapeutic effect of GO-cellulose was evaluated in vivo after the creation of two full-thickness wounds in the dorsum of rats (8 mm diameter). These wounds were randomly placed into two groups, the control group (10 wounds) and the GO-cellulose group (10 wounds), and monitored for gross and histopathological changes at 7 and 21 days after wound induction. MTT and Live/Dead assays showed excellent GO-cellulose cytocompatibility, whereas no difference in ECs viability was observed after culturing using conditioned media. GO-cellulose nanocomposite enhanced cell migration in the in vitro wound scratch assay. As compared to the control group, the GO-cellulose nanocomposite group's wound healing process was promoted in the in vivo rat skin wounds. Interestingly, wound re-epithelization and neovascularization were significantly accelerated in the GO-cellulose-treated rats. Furthermore, thick granulation tissue formation and intense collagen deposition were found in the GO-cellulose group. These findings showed that GO-cellulose has a promoting effect on skin wound healing, suggesting its promising and potential application in tissue regeneration., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: A pressure ulcer (PU) is an area of tissue trauma caused by continuous and prolonged pressure, often associated with hospitalised patients immobilised due to neurological problems, negatively affecting their quality of life, and burdening the public budget. The aim of this study was to report the follow-up, for 45 weeks, of three patients with neurological lesions due to trauma who subsequently developed PUs, and who were treated with a combination of photodynamic therapy (PDT), low level laser therapy (LLLT) and cellulose membrane (CM)., Method: PDT was mediated by the photosensitiser curcumin on a 1.5% emulsion base. Blue LED light at 450 nm was delivered continuously for 12 minutes at an irradiance of 30mW/cm 2 and total energy delivered to the tissue was 22J/cm 2 . LLLT was performed with 660 nm laser, punctuated and continuous, twice a week with parameters: spot size 0.04cm 2 , power of 40mW, 10 seconds per point, fluence of 10J/cm 2 and irradiance of 1000mW/cm 2 ., Results: All PUs had a significant reduction (range: 95.2-100%) of their area after 45 weeks of follow-up and two PUs had complete healing at 20 weeks and 30 weeks. All of the PUs showed a reduction in contamination with the PDT treatments in different proportions., Conclusion: From the results obtained, we conclude that the combination of PDT, LLLT and CM is a promising treatment for PU healing.

Introduction: Decannulation of the arteriovenous fistula (AVF) after each hemodialysis session requires a precise compression on the needle puncture site. The objective of our study was to evaluate the bleeding time (BT) needed to achieve hemostasis using WoundClot, an innovative hemostatic gauze, and to assess whether its long-term use can improve AVF preservation., Methods: This is a prospective single center study. Initially, the time to hemostasis after AVF decannulation was compared between WoundClot and cotton gauze in 24 prevalent hemodialysis patients. Thereafter, the patients continued to use WoundClot for 12 months and were compared to a control group consisting of 25 patients using regular cotton gauze. Follow-up data included parameters of dialysis adequacy, AVF interventions, and thrombotic events., Results: WoundClot use shortened significantly the time needed for hemostasis. Mean venous BT decreased by 3.99 (±4.6) min and mean arterial BT by 6.38 (±4.8) min when using WoundClot compared to cotton gauze (p < 0.001). At the end of the study, dialysis adequacy expressed by spKt/V was higher in the WoundClot group compared to control (1.73 vs. 1.53, respectively, p = 0.047). Although patients in WoundClot group had a higher baseline BT, arterial and venous pressures did not differ between the groups after a median follow up of 10.8 months. AVF thrombosis rate was similar between the groups., Conclusions: WoundClot hemostatic gauze significantly reduced the time required for hemostasis after AVF decannulation and may be associated with better AVF preservation. We suggest using WoundClot for arterial BT longer than 15 min and for venous BT longer than 12.5 min., (© 2021 S. Karger AG, Basel.)

Objective: Controlling infection and promoting healing should be the aims of hard-to-heal diabetic ulcer treatment, along with improving a patient's general condition and their blood sugar control. Many hard-to-heal diabetic ulcers present with cavities, tracks or a combination of these. There is a new biocellulose (with a nanosilver dressing) which has the ability to contour around and conform to the irregular surface of a wound bed. The purpose of this study was to evaluate its efficacy compared with a silver sulfadiazine cream, for hard-to-heal diabetic ulcer treatment., Methods: In this randomised control trial, patients with hard-to-heal diabetic ulcers were divided into two equal-sized groups: treatment with the biocellulose with blue nanosilver (experimental group), and treatment with silver sulfadiazine cream group (control group). Cotton gauze was used as the secondary dressing for both groups. Demographic data, wound size, wound classification, wound photography and bacterial cultures were recorded at the beginning of the study. Wounds were debrided as necessary. Dressings were changed twice daily in the control group, and every three days in the experimental group., Results: A total of 20 patients took part in the study (10 patients in each group). The highest mean wound healing rates were 91.4% in the experimental group and 83.9% in the control group. No wound infections or adverse effects from the dressings were detected in either group., Conclusion: In this study, biocellulose with blue nanosilver adapted well to the wound bed. Wound reduction was greater in the experimental group than the control group. Biocellulose with blue nanosilver could therefore be a good choice for hard-to-heal diabetic ulcer treatment, due to its good healing rates and minimal care requirements.

Avulsion of the nail plate is the most accomplished surgical procedure among the nail apparatus surgeries. Since it is not possible to use the removed nail to cover the nail bed, some materials have been suggested, however, they are generally not available for use and often at a high cost. To evaluate the use of Bacterial Cellulose (BC) dressing as a biological nail (Bio-Nail) after partial or total avulsion of the nail plate. Twenty-six candidates for nail avulsion, were randomized into two groups: Control, using Vaseline with gauze (11 patients) and Experimental group, BC group, using the Bio-Nail (15 patients). The patients were followed up during the 180-day period. The distribution of the patients in the groups was homogeneous for both sociodemographic and clinical data. The occurrence of infection (1 case in the control group) was not statistically relevant. The BC group had lower pain intensity (p = 0.011) with earlier temporal resolution when compared to the control group (p = 0.003). The BC group presented earlier reepithelization (p = 0.022) and better quantitative (p = 0.021) and qualitative conditions (p = 0.011) for the exudate. Regarding satisfaction, all the patients were satisfied. Good preservation of the nail plate area was observed in the BC group at the end of the 180-day period (p = 0.024). Average time of BC dressing permanence was 16.4 ± 7.1 days. BC showed to be appropriate as a dressing after partial or total avulsion of the nail plate. BC is a Bio-Nail promising for nail bed healing.

Objective: To compare the efficacy and safety of HemoStyp (United Health Products, US), a neutralised oxidised regenerated cellulose (NORC) and Surgicel (Johnson & Johnson, US), an oxidised regenerated cellulose (ORC), in the management of bleeding of surgical wounds during abdominal, thoracic and vascular surgeries., Method: This study was a prospective, non-inferiority, multicentre, randomised, open-label trial. Surgical procedures were performed according to expected standard of care and in compliance with all relevant laws and institutional guidelines. Patients who developed Lewis Bleeding Scale grade 1 and grade 2 bleeds not controlled through conventional techniques were randomised to either the NORC or ORC treatment arms. Bleeding was measured every 30 seconds after treatment, ending at five minutes after haemostasis was achieved or at 10 minutes if haemostasis was not achieved., Results: A total of 236 patients were included in the study. There was a total of seven adverse events in the study, none of which had causality related to either the NORC or ORC. For all surgical procedures, haemostasis was achieved more quickly with the NORC than the ORC (p<0.0001). In addition, haemostasis for all patients was achieved in under two minutes for the NORC compared with 81% of patients in the ORC groups. For Lewis Bleeding Scale grade 1 bleeds, the median time to control bleeding was 24 seconds in the NORC group and 51 seconds for the ORC group. For grade 2 bleeds, time to control bleeding was 76 seconds and 116 seconds, respectively., Conclusion: For patients in this study, haemostasis was achieved more quickly in the NORC treatment group compared with the ORC group, in patients with Lewis grade 1 or 2 bleeds caused by surgical wounds generated during abdominal, thoracic and vascular surgeries.

Cellulose derivatives represent a viable alternative to pure cellulose due to their solubility in water and common organic solvents. This, coupled with their low cost, biocompatibility, and biodegradability, makes them an attractive choice for applications related to the biomedicine and bioanalysis area. Cellulose derivatives-based composites with improved properties were researched as films and membranes for osseointegration, hemodialysis and biosensors, smart textile fibers, tissue engineering scaffolds, hydrogels and nanoparticles for drug delivery. The different preparation strategies of these polymeric composites as well as the most recent available experimental results were described in this review. General aspects such as structure and properties of cellulose extracted from plants or bacterial sources, types of cellulose derivatives and their synthesis methods were also discussed. Finally, the future perspectives related to composites based on cellulose derivatives were highlighted and some conclusions regarding the reviewed applications were drawn., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Acute and chronic skin wounds due to burns, pressure injuries, and trauma represent a substantial challenge to healthcare delivery with particular impacts on geriatric, paraplegic, and quadriplegic demographics worldwide. Nevertheless, the current standard of care relies extensively on preventive measures to mitigate pressure injury, surgical debridement, skin flap procedures, and negative pressure wound vacuum measures. This article highlights the potential of adipose-, blood-, and cellulose-derived products (cells, decellularized matrices and scaffolds, and exosome and secretome factors) as a means to address this unmet medical need. The current status of this research area is evaluated and discussed in the context of promising avenues for future discovery.

The preparation of microcapsules composed by natural materials have received great attention, as they represent promising systems for the fabrication of micro-containers for controlled loading and release of active compounds, and for other applications. Using polysaccharides as the main materials is receiving increasing interest, as they constitute the main components of the plant cell wall, which represent an ideal platform to mimic for creating biocompatible systems with specific responsive properties. Several researchers have recently described methods for the preparation of microcapsules with various sizes and properties using cell wall polysaccharide nanomaterials. Researchers have focused mostly in using cellulose nanomaterials as structural components in a bio-mimetic approach, as cellulose constitutes the main structural component of the plant cell wall. In this review, we describe the microcapsules systems presented in the literature, focusing on the works where polysaccharide nanomaterials were used as the main structural components. We present the methods and the principles behind the preparation of these systems, and the interactions involved in stabilizing the structures. We show the specific and stimuli-responsive properties of the reported microcapsules, and we describe how these characteristics can be exploited for specific applications.

We demonstrate the viability of using ultra-thin sheets of microbially grown nanocellulose to build functional medical sensors. Microbially grown nanocellulose is an interesting alternative to plastics, as it is hydrophilic, biocompatible, porous, and hydrogen bonding, thereby allowing the potential development of new application routes. Exploiting the distinguishing properties of this material enables us to develop solution-based processes to create nanocellulose printed circuit boards, allowing a variety of electronics to be mounted onto our nanocellulose. As proofs of concept, we have demonstrated applications in medical sensing such as heart rate monitoring and temperature sensing-potential applications fitting the wide-ranging paradigm of a future where the Internet of Things is dominant.

Objective: Skin graft donor site management is a concern particularly for elderly patients and patients with poor wound healing competence, and also because donor sites are a source of pain and discomfort. Although different types of dressings exist, there is no consensus regarding optimal dressing type on donor site care to promote healing, reduce pain, and improve patients' comfort. Approach: This prospective, single-center clinical trial evaluated the performance of nanofibrillar cellulose (NFC) wound dressing (FibDex ® by UPM-Kymmene Corporation) for treatment of donor sites compared with a polylactide-based copolymer dressing. The study enrolled 24 patients requiring skin grafting with mean age of 49 ± 18. The primary outcome measure was wound healing time. Secondary outcomes, the epithelialization, subjective pain, the scar appearance assessed using the Patient and Observer Scar Assessment Scale (POSAS), and skin elasticity and transepidermal water loss (TEWL), were evaluated at 1 and 6 months postoperatively. Results: No statistically significant differences were observed between NFC and copolymer dressings regarding wound healing time, epithelialization, experience of pain, or TEWL. Significant differences were observed in the POSAS results for thickness and vascularity in the Observer score, in the favor of NFC over copolymer dressing. Moreover, skin elasticity was significantly improved with NFC dressing in terms of viscoelasticity and elastic modulus at 1 month postoperatively. Innovation: NFC dressing is a new, green sustainable product for wound treatment without animal or human-origin components. Conclusion: NFC dressing provides efficient wound healing at skin graft donor sites and is comparable or even preferable compared with the copolymer dressing., Competing Interests: K.L. and M.K. represent UPM-Kymmene Corporation, which is the manufacturer of NFC dressing. Other authors do not have potential conflicts of interest associated with this publication. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article., (© Raili Koivuniemi, et al. 2019; Published by Mary Ann Liebert, Inc.)

Carbazate groups were grafted on the commercial cellulose membrane (CM) to specifically scavenge the carbonylated proteins for hemodialysis. It confirmed that carbazate groups were successfully covalently attached on the CMs by XPS and EDS, and the modified CMs still saved their original morphology and crystalline structures by SEM and XRD. Furthermore, the modified CMs presented favorable physicochemical stability at wide pH range from 2.5 to 7.4. It was also found that the carbazate modified CMs could selectively remove carbonylated proteins from acrolein treated bovine serum albumin (BSA) or ESRD patient's blood serum in PBS buffer. The modified CMs showed the potential to be utilized as the substitute of dialysis membranes in hemodialysis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Functionality of the facial nerve is cosmetically important. While many techniques have been investigated, early and effective treatment for traumatic facial nerve paralysis remains challenging. Here, we aim to examine bacterial cellulose (BC) as a new tubularization material for improving facial nerve regeneration., Methods: Our study was performed on 40 female Sprague Dawley rats. Rats were randomly divided into four groups, with 10 rats per group. In all rats, the main trunk of the facial nerve was completely cut 8 mm before the branching point. For repairing the facial nerve, in group 1, the nerve was left to recover spontaneously (control group); in group 2, it was repaired by primary suturing (8.0 Ethilon sutures, Ethicon); in group 3, BC tubes alone were used to aid nerve repair; and in group 4, both BC tubes and primary sutures (8.0 Ethilon sutures) were used. After 10 weeks, the facial nerve regeneration was evaluated by the whisker movement test and electrophysiologically (nerve stimulation threshold and compound muscle action potential). Nerve regeneration was assessed by calculating the number of myelinated nerve fibers, and by microscopically evaluating the amount of regeneration and fibrosis., Results: No significant difference was observed among the groups in terms of whisker movement and electrophysiological parameters (P > 0.05). We found that the numbers of regenerating myelinated fibers were significantly increased (P < 0.05) when BC tubes were used as a nerve conduit., Conclusions: BC can be easily shaped into a hollow tube that guides nerve axons, resulting in better nerve regeneration after transection.

Objective: to evaluate the use of a bacterial cellulose biopolymer film and gel dressing in the treatment of patients with ischemic wounds submitted to lower limb revascularization., Methods: we conducted a randomized clinical trial in the Angiology and Vascular Surgery outpatient clinic of the Clinics Hospital of the Federal University of Pernambuco, between January 2017 and December 2018. We followed 24 patients after lower limb revascularization, divided into two groups: Experimental, treated with bacterial cellulose biopolymer film and gel, and Control, treated with essential fatty acids. Patients attended weekly appointments to change dressings and had their wound healing processes evaluated over a period of 90 days., Results: the reduction of the ischemic wounds' areas after 30 days was 4.3cm2 (55%) on average for the experimental group, and the 5.5cm2 (48.5%) for the control group (p>0.05). The complete healing rate at 90 days was 34.8%, 50% in the experimental group and 18.2% in the control group (p=0.053)., Conclusion: the bacterial cellulose biopolymer film associated with gel can be used as a dressing in the treatment of ischemic wounds of patients undergoing revascularization of the lower limbs.

Objective: To evaluate the efficacy of a biocellulose, a carboxymethyl cellulose and a normal saline wound dressing in the wound care management of epidermolysis bullosa (EB) skin wounds., Methods: This was a single-blind, randomised controlled trial involving wounds from patients with EB. Wounds were divided into three groups: group I with biocellulose wound dressing, group II with carboxymethyl cellulose wound dressing and group III with normal saline wound dressing as a control. All dressing changes and wound parameters were recorded. Observations were conducted every three days until complete wound closure or up to one month., Results: The outcomes of treatment of 36 wounds from four patients were evaluated in this study. Mean healing time in group I was seven days, eight days in group II and 14 days in group III. There were significant differences in healing times between group I and group III (p=0.0001) and between group II and III (p=0.001). The results showed a significant reduction in the percentage of wounds area on day three for each group: 51.7% in group I, 51.9% in group II, and 26% for group III. All wounds in groups I and II had healed at day 12 (100%) and at day 24 (100%) in group III. There were significant differences in the reduction of percentage wound area between group I and group III at day three (p=0.044) and day six (p=0.000), and between group II and III at day six (p=0.003)., Conclusion: The study demonstrates that both the biocellulose and the carboxymethyl cellulose wound dressings significantly reduced percentage wound areas and complete healing times compared with the normal saline wound dressing in EB skin wounds, demonstrating they are both equally good for wound care management in EB patients.

Promotion of wound healing is one of the most important fields in clinical medical research. This study aimed to evaluate the potential use of a new surface-structured bacterial cellulose(S-BC) biomaterial with human urine-derived stem cells (hUSCs) for wound healing. In vitro, EA.hy926 were inoculated on structured/non-structured bacterial cellulose, and the growth of EA.hy926 on bacterial cellulose in medium with/without conditioned medium of the hUSCs were observed to explore the effect of bacterial cellulose's surface structure and hUSCs-CM on vascular endothelial cell growth. In vivo, we covered wound surface with various BC materials and/or injected the hUSCs into the wound site on group BC, group S-BC, group hUSCs, group BC + hUSCs, group S-BC + hUSCs to evaluate the effect of S-BC and hUSCs on wound healing in rat full-thickness skin defect model. In vitro study, surface structure of S-BC could promote the growth and survival of EA.hy926, and the hUSCs-CM could further promote the proliferation of EA.hy926 on S-BC. In vivo study, wound healing rate of the group BC, group S-BC, group hUSCs was significantly accelerated, accompanied by faster re-epithelialization, collagen production and neovascularization than control group. It is note worthy that the effect of S-BC on wound healing was better than BC, the effect of S-BC + hUSCs on wound healing was better than BC + hUSCs. Moreover, the effect of S-BC combined with hUSCs on wound is better than treated with S-BC or hUSCs alone. All the findings suggest that the combination of S-BC and hUSCs could facilitate skin wound healing by promoting angiogenesis. This combination of the role of stem cells and biomaterial surface structures may provide a new way to address clinical wound healing problems., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Scaffold plays a critical role in stem cell differentiation and tissue regeneration. Composite scaffolds composed of bacterial cellulose (BC) and collagen (Col) in different ratios (1:1, 3:1, 5:1) were fabricated in this study. The composite scaffolds exhibit a well-organized interconnected porous structure, significantly better physical stability than Col scaffold, and more water uptake up to 400%. They were also favorable with cell attachment and growth. After osteogenic induction of umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) for 3 weeks, we found more up-regulated osteogenic markers (collagen type 1, osteocalcin, bone sialoprotein) and significantly elevated proteins and calcium deposition, particularly with BC/Col (5:1) scaffold. When PKH-26 pre-labelled MSC-loaded scaffolds were subcutaneously transplanted in a mouse model, they showed many PKH-26-labelled cells and positive signals of α-smooth muscle actin, for neovascularization in the BC/Col (5:1). The current work demonstrates that our BC/Col composites may be promising as a bone tissue-engineered scaffold., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The use of cellulose as an alternative to synthetic polymers might permit the decrease of environmental impacts by achieving more easily biodegradable or reusable materials. Recently, cellulose and inorganics are synergistically coupled to tailor promising functional hybrids with unique properties. The current review presents an overview of the recent trials for preparing cellulose/calcium phosphate hybrid materials and offers prospects for many new applications in diverse fields. During the whole review, different cellulose forms and cellulose derivatives are being explored as fillers or templates for the design of new functional materials and support for the loading of different calcium phosphate phases. The functionalization of cellulose with calcium phosphate was carried out to construct new and attractive physicochemical properties that are being exploited for different applications such as bone regeneration, drug delivery vehicles, dental repair and adsorption. The studying of cellulose/calcium phosphate hybrid materials is supported by increasing concern in providing smart materials that combine best of the calcium phosphate properties along with cellulose. The review also aims to study the driving forces and limitations towards structuring of cellulose/calcium phosphate hybrid materials. It appears that the use of cellulosic materials for constructing new hybrids is very promising for biomedical and environmental applications., (Copyright © 2019. Published by Elsevier B.V.)

Since early times, propolis has been used in folk medicine. The red propolis, collected in the northeast region of Brazil has been highlighted due to its popular use as an antimicrobial, with anti-inflammatory and healing properties, which are associated with its chemical composition. Here, we combine a bacterial membrane with red propolis to treat wounds of diabetic mice. This work aims to evaluate a biocurative from bacterial cellulose associated with red propolis in diabetic mice as wound healing model. Biocuratives from bacterial cellulose membrane and different extracts of red propolis were produced. The qualification and quantification of the presence of propolis chemical compounds in the membrane were investigated through high-resolution mass spectrometry (HRMS). Tests in vivo with biocuratives were performed on Swiss male diabetic mice induced by estroptozotocin. The animals were submitted to a surgical procedure and a single lesion was produced in the dorsal region, which was treated with the biocuratives. Macroscopic assessments were performed at 2, 7 and 14 postoperative days, and biopsies were collected on days 0, 7 and 14 for histological analysis, myeloperoxidase enzyme activity (MPO) and cytokines (TNF-α, IL-1β, and TGF-β). Altogether, ten compounds were identified in membranes and five were further quantified. The ethyl acetate extract showed more red propolis markers, and the most prevalent compound was Formononetin with 4423.00-2907.00 μg.g -1 . Macroscopic analyses demonstrated that the two groups treated with red propolis (GMEBT and GMEAE) showed significantly greater healing capabilities compared to the control groups (GS and GMS). An increase in leukocyte recruitment was observed, confirmed by the activity of the enzyme myeloperoxidase (MPO) in GMEBT and GMEAE groups. The levels of TNF-α were significantly higher in wounds stimulated with red propolis, as well as in TGF-β (GMEBT and GMEAE) on day 7. This was different from the IL-1β levels that were higher in the control groups (GS and GMS). In summary, the biocuratives produced in this work were able to accelerate the wound healing process in a diabetic mouse model. In this way, the traditional knowledge of red propolis activity helped to create a biotechnological product, which can be used for diabetic wound healing purpose., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Triblock poloxamer copolymer (PM) has been extensively utilized to deliver various ophthalmic pharmaceutical compounds. The aim of efficient ophthalmic drug delivery strategy is to attain the longer precorneal resident time and good bioavailability of drugs. In this pursuit, the influence of cellulose nanocrystals (CNC) on the in situ gelation behavior of PM and in vitro release of pilocarpine hydrochloride from the nanocomposites formulations was studied. The critical concentration of gelation of PM being 18% (wt/v) was dropped to 16.6% (wt/v) by the addition of a very low percentage of CNC. The reinforcing nature of CNC via H-bonding in the in situ nanocomposite gel also led to an increase in gel strength along with the sustained release of loaded drugs when compared with the pure PM gel. All formulations revealed that the drug release mechanism is controlled by the Fickian diffusion. Thus, the CNC has a significant effect on the gelation behavior, gel strength, and drug release kinetics of PM-CNC formulations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bacterial cellulose (BC) is a promising biopolymer with wound healing and tissue regenerative properties but lack of antimicrobial property limits its biomedical applications. Therefore, current study was proposed to combine wound healing property of BC with antimicrobial activity of montmorillonite (MMT) and modified montmorillonites (Cu-MMT, Na-MMT and Ca-MMT) to design novel artificial substitute for burns. Designed nanocomposites were characterized through Fe-SEM, FTIR and XRD. The antimicrobial activities of composites were tested against Escherichia coli, Salmonella typhimurium, Citrobacter fruendii, Pseudomonas aeruginosa, Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. Tissue regeneration and wound healing activities of the composites were assessed in burn mice model. Physico-chemical characterization confirmed the loading of MMT onto surface and BC matrix. Modified MMTs-BC nanocomposites showed clear inhibitory zone against the tested pathogens. Animals treated with modified MMTs-BC nanocomposites exhibited enhanced wound healing activity with tissue regeneration, reepithelialization, healthy granulation and vascularization. These findings demonstrated that modified MMTs-BC nanocomposites could be used as a novel artificial skin substitute for burn patients and scaffold for skin tissue engineering., (Copyright © 2018 Elsevier Ltd. All rights reserved.)