Nanomedicine-based strategies to improve treatment of cutaneous leishmaniasis.

Nanomedicine strategies were first adapted and successfully translated to clinical application for diseases, such as cancer and diabetes. These strategies would no doubt benefit unmet diseases needs as in the case of leishmaniasis. The latter causes skin sores in the cutaneous form and affects internal organs in the visceral form. Treatment of cutaneous leishmaniasis (CL) aims at accelerating wound healing, reducing scarring and cosmetic morbidity, preventing parasite transmission and relapse. Unfortunately, available treatments show only suboptimal effectiveness and none of them were designed specifically for this disease condition. Tissue regeneration using nano-based devices coupled with drug delivery are currently being used in clinic to address diabetic wounds. Thus, in this review, we analyse the current treatment options and attempt to critically analyse the use of nanomedicine-based strategies to address CL wounds in view of achieving scarless wound healing, targeting secondary bacterial infection and lowering drug toxicity.

Polysucrose hydrogel and nanofiber scaffolds for skin tissue regeneration: Architecture and cell response.

Scaffolds capable of mediating overlapping multi-cellular activities to support the different phases of wound healing while preventing scarring are essential for tissue regeneration. The potential of polysucrose as hydrogels and electrospun mats for wound healing was evaluated in vitro by seeding fibroblasts, endothelial cells and macrophages either singly or in combination. It was found that the scaffold architecture impacted cell behaviour. Electrospun mats promoted fibroblasts flattened morphology while polysucrose methacrylate (PSucMA) hydrogels promoted fibroblast spheroids formation, accentuated in the presence of endothelial cells. Hydrogels exhibited lower inflammatory response than mats and curcumin loaded scaffolds reduced TNF-α production. In vivo biocompatibility of the hydrogels tested on Wistar rats was superior to electrospun mats. In vivo wound healing studies indicated that PSucMA hydrogels integrated the surrounding tissue with better cellular infiltration and proliferation throughout the entire wound region. PSucMA hydrogels led to scarless wound closure comparable with commercially available gels.

Assessing the mechanisms of action of natural molecules/extracts for phase-directed wound healing in hydrogel scaffolds.

Hydrogels are proving to be very versatile as wound healing devices. In addition to their capabilities of providing a moist cellular environment and adaptive mechanical properties mimicking the extracellular matrix, they allow the incorporation of small molecules, which have potential impacts on cellular behaviour, in their nanostructures. This strategy can allow for specific targeting of the different stages of wound healing namely hemostasis, inflammation, and proliferative and remodelling phases. The latter include interlinked processes such as angiogenesis, collagen synthesis, growth factor release, collagen maturation and re-epithelialization. In this review, we attempt to match the mechanisms of action of natural molecules/extracts to the different stages of wound healing so that they can be used in a novel approach of multiphase-directed tissue regeneration using loaded hydrogel scaffolds.

Correlating in vitro performance with physico-chemical characteristics of nanofibrous scaffolds for skin tissue engineering using supervised machine learning algorithms.

The engineering of polymeric scaffolds for tissue regeneration has known a phenomenal growth during the past decades as materials scientists seek to understand cell biology and cell-material behaviour. Statistical methods are being applied to physico-chemical properties of polymeric scaffolds for tissue engineering (TE) to guide through the complexity of experimental conditions. We have attempted using experimental in vitro data and physico-chemical data of electrospun polymeric scaffolds, tested for skin TE, to model scaffold performance using machine learning (ML) approach. Fibre diameter, pore diameter, water contact angle and Young's modulus were used to find a correlation with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of L929 fibroblasts cells on the scaffolds after 7 days. Six supervised learning algorithms were trained on the data using Seaborn/Scikit-learn Python libraries. After hyperparameter tuning, random forest regression yielded the highest accuracy of 62.74%. The predictive model was also correlated with in vivo data. This is a first preliminary study on ML methods for the prediction of cell-material interactions on nanofibrous scaffolds.

Modulating matrix-multicellular response using polysucrose-blended with poly-L-lactide or polydioxanone in electrospun scaffolds for skin tissue regeneration.

Polysucrose (PSuc) is hydrophilic, has excellent biocompatibility with cells as a density gradient and is resistant to enzymes. Its use in electrospun mats for tissue engineering applications has not been investigated due to its amorphous nature. For spinnability and robustness, polysucrose was blended with poly-L-lactide (PLLA) and polydioxanone (PDX) respectively and electrospun into nanofibrous mats. Interaction with cells was assessed using L929 mouse fibroblasts and HaCaT keratinocytes separately and in co-culture. Effect of parameters such as porosity, fiber diameter, surface wettability and mechanical properties of mats on cell-scaffold interactions was studied. Depending on nature and composition of mats, fibroblasts showed dendritic, spindle or round cell morphologies along with the formation of lamellipodia, filopodia, fibrillar or fiber-like projections of 100 nm and 200-300 nm in diameter respectively from the periphery or center of cells. Granular extracellular matrix was formed on both PLLA-PSuc and PDX-PSuc 50-50 seeded with keratinocytes. Growth of keratinocytes was enhanced in co-culture with fibroblasts with the formation of a skin-like layer. Both cells showed the ability to form multilayer structures. The mats maintained their physical integrity during the period of study. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3275-3291, 2018.