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

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

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

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

Study of the SARS-CoV-2 genomic data generation to evaluate the introduction of genomics in epidemiological surveillance and public health decision making.

Introduction: the limited number of equipped laboratories and the lack of expertise left Africa lagging behind in terms of contribution in genomic data generation. The COVID-19 pandemic has drawn the attention of all public health stakeholders so that it can be used as a marker of the efforts that public health systems can produced. The main purpose of the present analytical study was to evaluate the contribution of the African continent in the genomic surveillance of SARS-CoV-2. Methods: data from the two most popular genomic databases on SARS-CoV-2 (GISAID EpiCov and NCBI Virus) were extracted and analyzed. Comparisons were made using the sequencing ratio which represents the number of genomic sequence published over one thousands confirmed cases. Results: considering continental blocks, the Africa occupied the fourth place after Oceania, Europe and North America based on sequencing ratios. However, when the considered comparison parameter is the number of sequences, the African continent was the fifth contributor after Europe, North America, Asia and South America. Conclusion: the study showed that African countries have effectively integrated the genomic data generation in the public health response strategies but the effective use of these data for a perfect surveillance is not clearly established. There is a need for capacity building in genomic data analyses for a better response to public health threats in Africa.

Prevention and treatment of COVID-19: Focus on interferons, chloroquine/hydroxychloroquine, azithromycin, and vaccine.

The ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drawn the attention of researchers and clinicians from several disciplines and sectors who are trying to find durable solutions both at preventive and treatment levels. To date, there is no approved effective treatment or vaccine available to control the coronavirus disease-2019 (COVID-19). The preliminary in vitro studies on viral infection models showed potential antiviral activities of type I and III interferons (IFNs), chloroquine (CQ)/hydroxychloroquine (HCQ), and azithromycin (AZM); however, the clinical studies on COVID-19 patients treated with CQ/HCQ and AZM led to controversies in different regions due to their adverse side effects, as well as their combined treatment could prolong the QT interval. Interestingly, the treatment with type I IFNs showed encouraging results. Moreover, the different preliminary reports of COVID-19 candidate vaccines showcase promising results by inducing the production of a high level of neutralizing antibodies (NAbs) and specific T cell-mediated immune response in almost all participants. The present review aims to summarize and analyze the recent progress evidence concerning the use of IFNs, CQ/HCQ, and AZM for the treatment of COVID-19. The available data on immunization options to prevent the COVID-19 are also analyzed with the aim to present the promising options which could be investigated in future for sustainable control of the pandemic.

Silk sericin-enhanced microstructured bacterial cellulose as tissue engineering scaffold towards prospective gut repair.

As a first step towards the production of functional cell sheets applicable for the regeneration of gut muscle layer, microstructured bacterial cellulose (mBC) was assessed for its ability to support the growth of enteric nervous system (ENS) and gut smooth muscle cells (SMCs). To improve the cellular response, mBC was modified with silk sericin (SS) which has renowned abilities in supporting tissue regeneration. While SS did not impair the line structures imparted to BC by PDMS templates, similarly to the patterns, it affected its physical properties, ultimately leading to variations in the behavior of cells cultured onto these substrates. Enabled by the stripes on mBC, both SMCs and ENS cells were aligned in vitro, presenting the in vivo-like morphology essential for peristalsis and gut function. Interestingly, cell growth and differentiation remarkably enhanced upon SS addition to the samples, indicating the promise of the mBC-SS constructs as biomaterial not only for gut engineering, but also for tissues where cellular alignment is required for function, namely the heart, blood vessels, and similars.

Cancer hallmarks and malignancy features: Gateway for improved targeted drug delivery.

Cancer chemotherapy is mainly based on the use of cytotoxic compounds that often affect other tissues, generating serious side effects which deteriorate the quality of life of patients. Recent advancements in targeted drug delivery systems offer opportunities to improve the efficiency of chemotherapy, by the use of smaller drug doses with reduced side effects. In the gene therapy approach, this consists in improving the transformation potential of the gene delivery system. Interestingly, these systems further provide good platforms for the delivery of hydrophobic and low-bioavailability compounds, while facilitating the penetration of the blood-brain barrier. The present report provides an overview of biologically relevant cancer hallmarks that can be exploited to design effective delivery vehicles that release cytotoxic compounds specifically in cancer tissues, in a targeted manner. The relevance of each cancer marker is presented, with particular emphasis on the generation of these hallmarks and their importance in cancer cell biology.

Microstructured Multilevel Bacterial Cellulose Allows the Guided Growth of Neural Stem Cells.

Repeated photolithographic and etching processes allow the production of multileveled polymer microstructures that can be used as templates to produce bacterial cellulose with defined surfaces on demand. By applying this approach, the bacterial cellulose surface obtains new properties and its use for culturing neural stem cells cellulose substrate topography influences the cell growth in a defined manner.

Silk Sericin-Functionalized Bacterial Cellulose as a Potential Wound-Healing Biomaterial.

Bacterial cellulose (BC) is a polysaccharide known as a suitable matrix for proper wound healing. To improve this ability, BC was functionalized with silk sericin (SS) that has cytoprotective and mitogenic effects. The composites obtained by solution impregnation were stabilized by hydrogen bonds, and SS could be released in a controlled manner. The constructs were highly porous with interconnected pores allowing for high water uptake that varied with the SS concentration used for sample preparation. While SS did not disrupt the stability of the BC network, soluble SS diffusing from the composites did not influence keratinocyte growth but enhanced fibroblast proliferation, which would further optimize the wound healing process and improve extracellular matrix production, accelerating healing. Further, improved cell viability was observed upon the composites. Because of their attractive structure and properties, these BC-SS biomaterials represent potential candidates not only for wound dressing applications but also for tissue engineering.

Silk sericin: A versatile material for tissue engineering and drug delivery.

Sericin is an inexpensive glycoprotein obtained as a by-product in the silk industry. Its variable amino acid composition and diverse functional groups confer upon it attractive bioactive properties, which are particularly interesting for biomedical applications. Because of its antioxidant character, moisturizing ability, and mitogenic effect on mammalian cells, sericin is useful in cell culture and tissue engineering. Its positive effects on keratinocytes and fibroblasts have led to the development of sericin-based biomaterials for skin tissue repair, mainly as wound dressings. Additionally, sericin can be used for bone tissue engineering owing to its ability to induce nucleation of bone-like hydroxyapatite. Stable silk sericin biomaterials, such as films, sponges, and hydrogels, are prepared by cross-linking, ethanol precipitation, or blending with other polymers. Sericin may also be employed for drug delivery because its chemical reactivity and pH-responsiveness facilitate the fabrication of nano- and microparticles, hydrogels, and conjugated molecules, improving the bioactivity of drugs. Here, we summarized the recent advancements in the study of silk sericin for application in tissue engineering and drug delivery.