Bacterial cellulose as an ideal potential treatment for burn wounds: A comprehensive review.

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.

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.

Efficacy of four different hemostatic agents in thyroid surgery in reducing the amount of post-operative fluid collection.

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.

Combining microfluidics and coaxial 3D-bioprinting for the manufacturing of diabetic wound healing dressings.

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.

Super-Elastic Carbonized Mushroom Aerogel for Management of Uncontrolled Hemorrhage.

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.

Nanocrystalline Cellulose Cures Constipation via Gut Microbiota Metabolism.

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.

Bacterial Cellulose as a Versatile Biomaterial for Wound Dressing Application.

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.

Targeting polysaccharides such as chitosan, cellulose, alginate and starch for designing hemostatic dressings.

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.

Cellulose-Conjugated Copper-Oxide Nanoparticles for the Treatment of Ethanol-Induced Gastric Ulcers in Wistar Rats.

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-ß, 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 (CuI/IIO NPs) synthesized under environmentally friendly conditions. We have evaluated the effects of cellulose-conjugated CuI/IIO NPs against ethanol-induced gastric ulcer in Wistar rats. The cellulose-conjugated CuI/IIO 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-1ß), and other inflammatory biomarkers such as myeloperoxidase (MPO) activity and nitric oxide (NO) levels. The current study's findings suggest that cellulose-conjugated CuI/IIO NPs exerted antiulcer effects on the preclinical rat model and have promising potential as a novel therapeutic agent for the treatment of gastric ulcers.

131I-αPD-L1 immobilized by bacterial cellulose for enhanced radio-immunotherapy of cancer.

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 131I-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 131I-labeled αPD-L1 within tumors, which could reduce the side effect stemmed from the nonspecific 131I distribution in normal tissues. The potent long-term RIT of 131I, combined with ICB by αPD-L1, could effectively restrain the growth of primary tumor in mice. In addition to the direct killing effect, 131I-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.

The biomechanical efficacy of a dressing with a soft cellulose fluff core in protecting prone surgical patients from chest injuries on the operating table.

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.

Evaluating tolerability of resistant starch 2, alone and in combination with minimally fermented fibre for patients with irritable bowel syndrome: a pilot randomised controlled cross-over trial.

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.

Biosynthetic cellulose compared to porcine xenograft in the treatment of partial-thickness burns: A randomised clinical trial.

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.

A pilot and open trial to evaluate topical Bacterial Cellulose bio-curatives in the treatment of cutaneous leishmaniasis caused by L. braziliensis.

The treatment of cutaneous leishmaniasis (CL) in Brazil using pentavalent antimony (Sbv) is associated with a high failure rate and long time to heal. Moreover, standard Sbv treatment cures only 50-60% of the cases. In this pilot clinical trial, we evaluated the topical use of bacterial cellulose (BC) bio-curatives + Sbv 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 Sbv alone or parenteral Sbv plus topically applied BC bio-curatives. CL patients treated with Sbv + topical BC bio-curatives had a significantly higher cure rate at 60 days post initiation of treatment compared to CL patients treated with Sbv 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 Sbv in favoring healing of CL lesions caused by L. braziliensis, at an early time point.

Modified montmorillonite-bacterial cellulose composites as a novel dressing system for pressure injury.

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.

Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy.

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 ß-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.

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.

Dialdehyde Nanocrystalline Cellulose as Antibiotic Substitutes against Multidrug-Resistant Bacteria.

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.

Graphene oxide-cellulose nanocomposite accelerates skin wound healing.

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.