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Natural molecule/extract-loaded hydrogel scaffold platform for multi-phase wound healing.

Marine sponges represent a valuable source of cyclodepsipeptides with anti-cancer potential.

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.

The use of non-invasive scaffold materials which can mimic the innate piezoelectric properties of biological tissues is a promising strategy to promote native tissue regeneration. Piezoelectric and cell instructive electrospun core-shell PDX/PHBV mats have been engineered to promote native tissue and skin regeneration. In depth physicochemical characterisation, in vitro and in vivo studies of a rat model showed that the 20/80 PDX/PHBV composition possessed the right balance of physicochemical and piezoelectric properties leading to enhanced fibroblast stimulation, proliferation and migration, reduced fibroblast-mediated contraction and macrophage-induced inflammation, improved keratinocyte proliferation, proper balance between endothelial cell phenotypes, decreased in vivo fibrosis and accelerated in vivo scarless wound regeneration. Overall, this study highlights the importance of exploiting cell-material interactions to match tissue biological needs to sustain the wound healing cascade.

In a previous article, we reported on the physico-chemical properties of cellulose-based scaffolds derived from sugar-cane bagasse and their preliminary in vitro assessment. In view of skin tissue regeneration, we here present our findings of an extensive in vitro testing of these scaffolds using key cells involved in the wound healing cascade namely fibroblasts, keratinocytes, endothelial cells and macrophages either singly or in various combinations to mimic in vivo conditions. Inflammation was quantified using TNF-α. In vivo biocompatibility as well as wound healing potential of the scaffolds was demonstrated using Wistar rats. Finally, we discuss the effect of curcumin-loaded scaffolds on inflammation and angiogenesis in vitro and in vivo. Nanosilica extracted from sugar-cane bagasse ash was also loaded in the scaffolds and its effect on biological response was assessed.

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.

Genomics policy development involves assessing a wide range of issues extending from specimen collection and data sharing to whether and how to utilize advanced technologies in clinical practice and public health initiatives. A survey was conducted among African scientists and stakeholders with an interest in genomic medicine, seeking to evaluate: 1) Their knowledge and understanding of the field. 2) The institutional environment and infrastructure available to them. 3) The state and awareness of the field in their country. 4) Their perception of potential barriers to implementation of precision medicine. We discuss how the information gathered in the survey could instruct the policies of African institutions seeking to implement precision, and more specifically, genomic medicine approaches in their health care systems in the following areas: 1) Prioritization of infrastructures. 2) Need for translational research. 3) Information dissemination to potential users. 4) Training programs for specialized personnel. 5) Engaging political stakeholders and the public. A checklist with key requirements to assess readiness for implementation of genomic medicine programs is provided to guide the process from scientific discovery to clinical application.

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.

The potential of electrospun polydioxanone (PDX) mats as scaffolds for skeletal tissue regeneration was significantly enhanced through improvement of the cell-mediated biomimetic mineralization and multicellular response. This was achieved by blending PDX ( i) with poly(hydroxybutyrate- co-valerate) (PHBV) in the presence of hydroxyapatite (HA) and ( ii) with aloe vera (AV) extract containing a mixture of acemannan/glucomannan. In an exhaustive study, the behavior of the most relevant cell lines involved in the skeletal tissue healing cascade, i.e. fibroblasts, macrophages, endothelial cells and preosteoblasts, on the scaffolds was investigated. The scaffolds were shown to be nontoxic, to exhibit insignificant inflammatory responses in macrophages, and to be degradable by macrophage-secreted enzymes. As a result of different phase separation in PDX/PHBV/HA and PDX/AV blend mats, cells interacted differentially. Presumably due to varying tension states of cell-matrix interactions, thinner microtubules and significantly more cell adhesion sites and filopodia were formed on PDX/AV compared to PDX/PHBV/HA. While PDX/PHBV/HA supported micrometer-sized spherical particles, nanosized rod-like HA was observed to nucleate and grow on PDX/AV fibers, allowing the mineralized PDX/AV scaffold to retain its porosity over a longer time for cellular infiltration. Finally, PDX/AV exhibited better in vivo biocompatibility compared to PDX/PHBV/HA, as indicated by the reduced fibrous capsule thickness and enhanced blood vessel formation. Overall, PDX/AV blend mats showed a significantly enhanced potential for skeletal tissue regeneration compared to the already promising PDX/PHBV/HA blends.

The primary aim of tissue engineering scaffolds is to mimic the in vivo environment and promote tissue growth. In this quest, a number of strategies have been developed such as enhancing cell–material interactions through modulation of scaffold physico–chemical parameters. However, more is required for scaffolds to relate to the cell natural environment. Growth factors (GFs) secreted by cells and extracellular matrix (ECM) are involved in both normal repair and abnormal remodeling. The direct use of GFs on their own or when incorporated within scaffolds represent a number of challenges such as release rate, stability and shelf-life. Small molecules have been proposed as promising alternatives to GFs as they are able to minimize or overcome many shortcomings of GFs, in particular immune response and instability. Despite the promise of small molecules in various TE applications, their direct use is limited by nonspecific adverse effects on non-target tissues and organs. Hence, they have been incorporated within scaffolds to localize their actions and control their release to target sites. However, scanty rationale is available which links the chemical structure of these molecules with their mode of action. We herewith review various small molecules either when used on their own or when incorporated within polymeric carriers/scaffolds for bone, cartilage, neural, adipose and skin tissue regeneration.

Oceans harbor a vast biodiversity that is not represented in terrestrial habitats. Marine sponges have been the richest source of marine natural products reported to date, and sponge-derived natural products have served as inspiration for the development of several drugs in clinical use. However, many promising sponge-derived drug candidates have been stalled in clinical trials due to lack of efficacy, off-target toxicity, metabolic instability or poor pharmacokinetics. One possible solution to this high clinical failure rate is to design drug delivery systems that deliver drugs in a controlled and specific manner. This review critically analyzes drugs/drug candidates inspired by sponge natural products and the potential use of drug delivery systems as a new strategy to enhance the success rate for translation into clinical use.

The main challenges of cancer drugs are toxicity, effect on wound healing/patient outcome and in vivo instability. Polymeric scaffolds have been used separately for tissue regeneration in wound healing and as anticancer drug releasing devices. Bringing these two together in bifunctional scaffolds can provide a tool for postoperative local tumor management by promoting healthy tissue regrowth and to deliver anticancer drugs. Another addition to the versatility of polymeric scaffold is its recently discovered ability to act as 3D cell culture models for in vitro isolation and amplification of cancer cells for personalized drug screening and to recapitulate the tumor microenvironment. This review focuses on the repurposing of 3D polymeric scaffolds for local tumor-wound management and development of in vitro cell culture models.

This article deals with an in-depth study of the thermal, mechanical and degradation behaviours of nanofibres from polydioxanone (PDX) and polyDL-3-methyl-1,4-dioxan-2-one (PMeDX) and a comparison with their blend films. Varying ratios of both polymers were blended and electrospun from solution. Electrospun fibres exhibited a melting transition at 109 °C independently of the PMeDX content, which corresponds to the melting of PDX nanofibres. As a result of the drawing process, PMeDX had a reduced plasticizing effect on PDX. In general, it was observed that overall crystallinity of the fibres decreased from 53% to 36% with increasing PMeDX content and this impacted on their mechanical properties. The Young's moduli decreased as the PMeDX content of the fibres increased. However, an increase in strain at break and peak stress was noted as a result of a decrease in the fibre diameter. AFM images of the electrospun fibres showed an increasing degree of morphological heterogeneity with increasing PMeDX content. Thermal degradation studies showed that electrospun mats were thermally more stable than blend films, as confirmed by a two-fold increase in activation energy. The hydrolytic degradation of the electrospun mats conducted in phosphate buffer solution at 37 °C showed that the degradation followed a surface erosion mechanism as opposed to bulk degradation observed for blend films. Degradation of fibres was found to be mainly dependent on their diameter. On the other hand, the degradation of blend films depended on the overall crystallinity of the blends. Electrospun PDX/PMeDX nanofibrous scaffolds were also subjected to cell viability studies with human dermal fibroblasts, in which they did not show illicit response and demonstrated excellent cell attachment and proliferation.

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 the machine learning (ML) approach. Fibre diameter, pore diameter, water contact angle and Young's modulus were used to find a correlation with 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.

The skin is a complex organ where multiple processes occur, and it contains biomacromolecules facilitating these processes. Wound healing and tissue regeneration are the two challenges faced by this organ as a result of injury. The plethora of investigations available on the use of a multitude of scaffolds, coupled with the expanding evidence of the skin's biomolecular processes, are both pointing toward the fact that a combination of different materials is required to address the complexity of the skin. These combinations should be able to strike the correct balance of bio-physico-chemical properties to match that of the skin. More importantly, they should also be commercially and clinically viable. This chapter guides the reader through (1) the biology of the skin and the processes of wound healing, (2) clinically available wound healing techniques, (3) strategies of material combination for scaffolds, and (4) the major challenges in 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.

Induced pluripotent stem cells (iPSCs) offer the possibility to accelerate tissue reconstruction through cell differentiation. The use of iPSCs in bone tissue engineering is promoted by next generation scaffolds which guide bone tissue repair and provide specific cues and molecular recognition to enhance differentiation as well as the bone forming ability of these cells. However, bone tissue repair faces additional challenges such as requirement for a consequent bone vasculature and exhaustion of stem cells in the aging adults. In this context, iPSC reprogramming seems to be unaffected by age and they have better pro-angiogenic potential as well as proliferation rate. The benefits of iPSCs using polymeric scaffolds include access to humanized in vitro models, triggering bone tissue reconstruction through a supply of bone cells via differentiation, compensating mesenchymal stem cells age-related deficiencies in osteodegenerative diseases, and enhancing angiogenesis.

Bagasse is a waste product of sugar extraction from sugar-cane with approximately 30% cellulose content. Cellulose was successfully extracted from sugar-cane bagasse using a modified mercerization-bleaching approach with a 40% yield. Extracted cellulose was converted to cellulose acetate for enhanced electrospinnability and blended with poly-l-Lactide or polydioxanone before solution electrospinning. Physico-chemical evaluation of the electrospun mats showed variable miscibility of blends. In vitro cell studies with L929 mouse fibroblast cells was quite conclusive as regards the biocompatibility of the blended mats with proliferative behavior of cells, extracellular matrix deposition and characteristic features of healthy cellular response. MTT assay indicated that the cellulose blended mats induced higher cell densities than the controls. Cellulose content influenced parameters such as fiber diameter, porosity and cell-matrix interaction of mats impacting on cell growth and behavior. Preliminary assessment of biomineralization potential of the mats by SEM showed nano-hydroxyapatite deposits on the electrospun fibers.

Skin tissue engineering for wound healing requires a biomimetic scaffold that provides a physical, chemical, and biological environment to guide cells toward regeneration. The nanofibrous architecture provided by electrospun scaffolds, as well as the ability to tailor their surface chemistry and offer controlled delivery of bioactive agents, makes them a promising candidate for skin replacements. In this mini-review, we describe the wound healing process and the currently available engineered skin substitutes, motivating the need for a next generation of engineered skin scaffolds. We analyze how the polymeric constituents, microstructure, and biological milieu work together in electrospun scaffolds to promote a favorable behavior of skin cells. We provide a critical analysis of the optimization of physicochemical-structural properties of scaffolds and their in vivo biological performance in animal models, considering how the scaffolds perform on both a structural and biochemical level. Finally, we consider new perspectives and technological advances toward clinical implementation of electrospun scaffolds for wound healing. Wound healing especially in diabetic patients is problematic, and currently available treatment such as dermal substitutes present various limitations. To improve upon the currently available products, the development of polymeric nanoscaffolds on which dermal cells have been seeded proves to be more effective to regenerate and remodel tissue. This review discusses the choice of the polymers, the fabrication of mats at the nanoscale, the type of biological agents required to guide healing, and the results of in vitro and in vivo studies and how they may be further improved and scaled up toward clinical implementation.

Cross-linked polysucrose hydrogels were synthesized for the first time from polysucrose grafted with methacrylic anhydride (MA) and crosslinked with ethylene glycol dimethacrylate (EGDMA). The addition of sucrose and polyethylene glycol monomethyl ether (mPEG5000) as porogens to the cross-linking reaction led to the formation of interconnected pores as well as a shift from a homogeneous non-porous to a heterogeneous porous surface. The potential of this family of hydrogels as biomaterial was assessed through the determination of the loading/release capacity of cationic and anionic dyes as model molecules and biocompatibility test with fibroblast cells. Cationic dyes showed high loading and sustained release over time attributed to the ionic interactions of the dyes with the hydrogels carrying a net negative charge. Anionic dyes on the other hand showed a rapid sinusoidal loading/release pattern. The release of the dyes was found to increase with increasing swelling capacity. NIH 3T3 fibroblast cells proliferated on hydrogels containing a porous structure and avoided the non-porous areas of the hydrogel surface.

We report in this paper on the enhanced efficacy of a physical mixture of two single anti-cancer loaded nanomicelles against PANC-1 and BxPC-3. Poly(vinyl pyrrolidone-b-polycaprolactone) (PVP-b-PCL) and poly(vinyl pyrrolidone-b-poly(dioxanone-co-methyl dioxanone)) (PVP-b-P(DX-co-MeDX)) were synthesized and successfully loaded with various anti-cancer drugs - gemcitabine (GEM), doxorubicin.HCl (DOX.HCl), doxorubicin.NH2 (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX). Spherical micelles of size 160-477 nm were obtained as characterized by DLS while sizes determined by TEM were in the range 140-250 nm. The hydrophobic drugs had a higher loading percentage efficiency compared to hydrophilic drugs in the trend PTX>DOX>5-FU>GEM>DOX.HCl whereas the drug release pattern followed the reverse trend in accordance with decreased polymer-drug interaction as quantified by the binding constant and micellar drug location. Cellular uptake studies showed that nanomicelles are taken up by pancreatic cancer cells into the cytoplasm and nucleus. The free nanomicelles were confirmed to be non-cytotoxic. A physical mixture of GEM loaded micelles and DOX.HCl loaded micelles of comparable size showed significantly higher cytotoxicity than either the free drug mixture or the individual single drug loaded micelles as confirmed by their IC50 values.

Novel electrospun materials for bone tissue engineering were obtained by blending biodegradable polyhydroxybutyrate (PHB) or polyhydroxybutyrate valerate (PHBV) with the anionic sulfated polysaccharide κ-carrageenan (κ-CG) in varying ratios. In both systems, the two components phase separated as shown by FTIR, DSC and TGA. According to the contact angle data, κ-CG was localized preferentially at the fiber surface in PHBV/κ-CG blends in contrast to PHB/κ-CG, where the biopolymer was mostly found within the fiber. In contrast to the neat polyester fibers, the blends led to the formation of much smaller apatite crystals (800 nm vs 7 μm). According to the MTT assay, NIH3T3 cells grew in higher density on the blend mats in comparison to neat polyester mats. The osteogenic differentiation potential of the fibers was determined by SaOS-2 cell culture for 2 weeks. Alizarin red-S staining suggested an improved mineralization on the blend fibers. Thus, PHBV/κ-CG fibers resulted in more pronounced bioactive and osteogenic properties, including fast apatite-forming ability and deposition of nanosized apatite crystals.

Since the late 1990s, there has been rapid multiplication of data on the anti-cancer properties of artemisinins. This article reviews the status of progress of artemisinin and its derivatives as anti-cancer agents in clinical trials, case reports, and in vitro/in vivo studies. Particular attention is laid on the combinations of artemisinins and synthetic chemodrugs to enhance the latter's efficacy. An attempt is here made to rationalize the synergistic effects of a few common anti-cancer drugs of the anthracycline, taxane, anti-metabolite, and platinum-based drug families. The various pathways that mediate the action of artemisinins as reported over the past decade are here summarized highlighting also the biomarkers that could be used to better predict the efficacy of the sesquiterpenoids. Their main action seems to be directed toward stalling tumor cell proliferation through cell cycle arrest mediated by reactive oxygen species (ROS). The emergence of artemisinins' nano-based formulations in combination with chemodrugs to enhance drug bioavailability and targeting as well as immunotherapy is also reviewed. The enhanced efficacy of artemisinin dimers compared to the parent molecules and standard chemotherapy is analyzed. While these therapies hold promises, it may be premature to conclude on their efficacy in the absence of clinical studies.

Cellulose has been extracted from a wide range of land resources, whereas it has been scarcely exploited from marine resources. Cellulose from green seaweeds can be extracted together with smaller molecules called ulvans. We have successfully extracted and characterized cellulose from Ulva sp. Solid state 13C NMR indicated the presence of ulvans in the cellulose extracts. The extracted cellulose was blended with polylactide and polydioxanone and electrospun into nanofibrous mats with a range of physico-chemical properties. These cellulose-based scaffolds were assessed in vitro using fibroblast cells and showed accelerated cell growth. In vivo biocompatibility studies using a Wistar rat model indicated the absence of foreign body response and enhanced angiogenesis.

Disbalanced reactive oxygen species (ROS) and glutathione (GSH) are characteristic features of tumor cells. High intracellular GSH concentration in tumor cells is a well-documented fact that leads to a very high reducing intracellular bio-milieu. High accumulation of ROS is known to occur in almost all cancers and can act as a two-edged sword during tumor development, by either promoting or inhibiting growth. These two features present unique opportunities to design drug delivery systems that are responsive to reduction or/and oxidation stimuli and has attracted accrued interest from researchers. These nanocarriers change their structural integrity, either through disassembly or degradation, to deliver their payload in the presence of the trigger. The aim of this chapter is to summarize the key developments in the design of materials with redox-responsive behaviour and their subsequent application in the field of nanomedicine targeting cancer. Strategies into exploiting both stimuli in a single nano drug delivery system to enhance therapeutic efficacy are also addressed.

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.

The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction between stroma and cancer cell. The two opposing schools of thought - non-depletion of the stroma vs its depletion - to better drug efficacy are here discussed. Disrupting stroma-cancer cell interaction to reduce tumor progression and promote apoptosis is identified as the new direction of treatment for PDAC. Clinical data have shown that elimination of fibrosis and blockade of the Hedgehog pathway in stroma effectively promote drug delivery to tumor site and apoptosis. Reduced stiffness of ECM, lower fibrosis, higher permeability and higher blood flow after stroma depletion increase drug delivery. Combination strategies involving selective stroma depletion coupled with chemotherapy is currently proving to be the most efficient at clinical level. Striking the right balance between fibrosis depletion and angiogenesis promotion resulting in enhanced drug delivery and apoptosis is a major challenge. The use of nano drug delivery devices coupled with stroma depletion is emerging as the next phase treatment for PDAC. The breakthrough to combat PDAC will likely be a combination of early diagnosis and the emerging chemotherapy strategies.

This review provides an overview of synthetic biodegradable polymer blends prepared for tissue engineering applications and aims at establishing structure-physicochemical-biological properties relationships. The characteristics of blends consisting of semi-crystalline/semi-crystalline and semi-crystalline/amorphous polymers are presented. Their biological properties such as degradability and biocompatibility and their biological performance as scaffolds in relation to cell adhesion, proliferation, infiltration, morphology and type are discussed. From available data, it can be deduced that miscibility influences physicochemical properties of the corresponding biodegradable polymeric blend scaffold, which in turn impacts on biological response. Immiscibility in polymer blends generally translates into good cell adhesion and proliferation. However, better cellular infiltration has been noted in compatible blends compared to immiscible blends. Factors such as crystallinity versus amorphous character, chirality, surface properties, degradation rate/products, mechanical properties and scaffold fabrication techniques are shown to have a major bearing on cell growth. © 2015 Society of Chemical Industry

In the first section of this paper, the existing and emerging nanotechnology-based cancer therapies--nanoparticles, drug conjugates, nanomicelles--are reviewed. In a second part, we present our original and unpublished findings on the sustained release of anti-cancer drugs such as paclitaxel, doxorubicin and camptothecin using block copolymer micelles [PEG-b-poly(dioxanone-co-methyl dioxanone)]. Copolymers with variable lengths of hydrophobic and hydrophilic blocks have been synthesized and successfully loaded with paclitaxel, doxorubicin and camptothecin anti-cancer drugs, with micelles size in the range 130-300 nm. Drug encapsulation efficiencies varied between 15% and 70% depending on drug and copolymer composition. The drug binding constants, which give a good insight into drug encapsulation and release, were evaluated from UV spectroscopy as we reported previously for anti-TB drugs. Through variation of the methyl dioxanone content of the copolymer, our systems can be tailored for sustained release of the different drugs.

Narcotic antagonists such as naltrexone (NTX) have shown some efficiency in the treatment of both opiate addiction and alcohol dependence. A few review articles have focused on clinical findings and pharmacogenetics of NTX, advantages and limitations of sustained release systems as well as pharmacological studies of NTX depot formulations for the treatment of alcohol and opioid dependency. To date, three NTX implant systems have been developed and tested in humans. In this review, we summarize the latest clinical data on commercially available injectable and implantable NTX-sustained release systems and discuss their safety and tolerability aspects. Emphasis is also laid on recent developments in the area of nanodrug delivery such as NTX-loaded micelles and nanogels as well as related research avenues. Due to their ability to increase the therapeutic index and to improve the selectivity of drugs (targeted delivery), nanodrug delivery systems are considered as promising sustainable drug carriers for NTX in addressing opiate and alcohol dependence.

The purpose of this review article is to showcase research in the area of polymeric nanobiomaterials and nanocarriers for drug delivery, especially on the economically fast-growing African continent where research in the field of advanced polymers and nanomedicine can play an important role in addressing crucial health issues. In biomaterials research, we have developed a new family of poly(ester-ether)s and shown that poly(methyl dioxanone) (PMeDX) can efficiently assist in fine-tuning mechanical and biological properties of scaffolds for tissue engineering applications. Interestingly, degradation of scaffold films was proceeded by bulk erosion, whereas that of fibres took place by a surface erosion mechanism. In vitro cell culture studies conducted using human dermal fibroblasts showed that the electrospun polydioxanone/poly(methyl dioxanone) (PDX/PMeDX) nanofibrous scaffolds supported better cell attachment and proliferation compared to electrospun PDX. Our main focus has been on the engineering of var...

The use of polymeric-based nanofibers has gained more and more attention during the past decade in the biomedical and pharmaceutical fields and as a result, nanotoxicology research is inevitable to satisfy the requirements of regulating agencies such as FDA as well as biosafety needs. Recent advances have witnessed the emergence of an increasing number of nanosized materials. While the number of potential applications related to the use of electrospun nanofibers continues to increase, studies to characterize their effects after exposure and to address their potential cytocompatibility are few in comparison. A comprehensive understanding of nano-bio and physico-chemical interactions is necessary from the early stage of nanomaterial conception to prevent pitfalls of materials failure at preclinical and clinical stages. This review presents a summary of both in vitro and in vivo cytocompatibility data currently available on synthetic and natural polymer-based electrospun nanofibers under investigation for tissue engineering applications. Cellular response dependence on cell type and nature of scaffold is also addressed.

A range of polyvinylpyrrolidone–polycaprolactone diblock copolymers with varying chain lengths were synthesized by Atom Transfer Radical Polymerisation (ATRP) using bromo-polycaprolactone as macroinitiator and copper(I) bromide/bipyridine catalytic system. The copolymers self-assembled in solution into core–shell micelles with sizes varying from 150 to 205 nm and critical micelle concentration of the order of 10−5 to 10−6 M. Front line anti-Tuberculosis drugs Rifampicin (RIF), Pyrazinamide (PZA) and Isoniazid (INH) were successfully encapsulated within the micelle hydrophobic core singly or in dual combination. The effect of length of hydrophobic and hydrophilic segments on drug loading, micelle size and drug release was investigated. Determination of binding constants showed that RIF binds more strongly to the micelle core than PZA and INH, leading to highest drug loading content. All drugs were released in vitro (PBS solution at 37 °C) in a sustained manner with zero-order kinetics and followed the order INH > PZA > RIF.

The promise of tissue engineering is the combination of a scaffold with cells to initiate the regeneration of tissues or organs. Engineering of scaffolds is critical for success and tailoring of polymer properties is essential for their good performance. Many different materials of natural and synthetic origins have been investigated, but the challenge is to find those that have the right mix of mechanical performance, biodegradability and biocompatibility for biological applications. This article reviews key polymeric properties for bone and vascular scaffold eligibility with focus on biopolymers, synthetic polymers and their blends. The limitations of these polymeric systems and ways and means to improve scaffold performance specifically for bone and vascular tissue engineering are discussed. c � 2013 Society of Chemical Industry

International audience; Polysaccharides from seaweeds are interesting materials for food and pharmaceutical applications such as drug delivery due to their biocompatibility and biodegradability. Extraction of these biopolymers is usually performed during several hours to obtain a significant extraction yield. In this paper, we report on a new process to extract alginates from brown seaweeds (Sargassum binderi and Turbinaria ornata) and carrageenans from red seaweeds (Kappaphycus alvarezii and Euchema denticulatum) with the assistance of ultrasound. The effect of several parameters (pH, temperature, algae/water ratio, ultrasound power and duration) was investigated to determine optimal extraction conditions. The extracted polysaccharides represented up to 55% of the seaweeds dry weight and were obtained in a short time (15–30 min) as compared to 27% in 2 h for conventional extraction. NMR, FTIR and SEC analysis were used to characterise the extracted polymers. Ultrasound allowed the reduction of extraction time without affecting the chemical structure and molar mass distribution of alginates and carrageenans.

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Three major chemotherapy strategies have emerged in the treatment of PDAC in the recent past: multiple drug combination, stroma depletion, and use of nanodrug therapy. Anti-diabetic metformin was shown to improve the outcome of a number of cancer types the first seminal report on an observational study published in 2005 and the first hospital-based case–control study on pancreatic cancer in 2009. In this review paper, we confront the findings of a selected number of epidemiological studies and clinical trials on the use of metformin in pancreatic cancer treatment with basic knowledge and research. We particularly emphasize on the point that contradictory clinical results likely originate from heterogeneous study design due to a trial and error approach rather than an evidence-based and scientific approach. A non-rigorous selection of patients suffering from PDAC and often a poor understanding of the biological mechanism of metformin coupled with lack of scientific data has led to general statements on metformin positive or negative action, another aspect which we highlight in the review. We here present a few pathways which in our opinion are predominant for pancreatic cancer specifically: mitochondrial activity, AMPK activation, mTOR inhibition, and decreased IGF-1R and HIF-1α expression. We stress on the need for a better stratification of patients and a more rigorous planning of clinical trials not only focusing on classical parameters but also on potential predictive biomarkers (AMPK, mTOR, HIF-1α, IGF-1R) and metformin dosage for positive outcome.

Colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) are the two most deadly forms of cancer. The last century has witnessed the emergence of new drugs such as 5-fluorouracil and gemcitabine that have shown some efficacy. Monotherapy limitations such as chemoresistance and low median survival, have led to combination chemotherapy: (i) two drugs, (ii) one drug and an antiepidermal growth factor receptor (GFR) agent or an antibody to block angiogenesis, and (iii) multiple drugs. Failure to prolong survival rate, chemoresistance, and toxicity encouraged probing into cancer biologics and the role of the tumor microenvironment. Studies have since shown that stromal tissue acts as a biological barrier, limiting drug delivery to tumor cells, but its depletion may have adverse effects on the latter. Nanotechnology brings new promises to CRC and PDAC treatment. Nanoparticles allow biodistribution and bioavailability via passive targeting (enhanced permeability and retention effect) and active targeting. New approaches such as nanoparticle albumin bound (nab)–paclitaxel, dual drug combination into nanoparticles or selective depletion of the stroma followed by nanoparticle delivery have raised new hopes for cancer therapy. This chapter discusses the biologics of these tumors and the intricacies of CRC and PDAC chemotherapy, with a focus on emerging nanotherapeutics targeting not only researchers but also students.

The synthesis and characterization of polycaprolactone (PCL) and poly(dioxanone-methyl dioxanone) (P(DX-co-MeDX)) block copolymers in a range of compositions of the two segments and with varying methyl dioxanone units is herein reported. The thermal properties of the copolymers were studied by differential scanning calorimetry (DSC) which revealed that copolymers exhibited two melting transitions ranging between 48 and 53 °C for the PCL segment and 71–79 °C for the P(DX-co-MeDX) segment. Copolymers exhibited only one crystallization exotherm which decreased as the MeDX content of the copolymer increased, thereby increasing miscibility of PCL and P(DX-co-MeDX) segments, a result also confirmed by scanning electron micrographs (SEM). Lastly, the kinetics of thermal degradation of PCL-b-P(DX-co-MeDX) copolymers were investigated by thermogravimetric analysis (TGA). Thermal degradation was shown to proceed in three distinct steps with the P(DX-co-MeDX) segment degrading in the first stage followed by the PCL ...

Various novel di-or tri-block copolymers with hydrophilic PEG and/or polylysine in association with hydrophobic polycaprolactone segments namely PEG-b-PolyLys and PEG-b-PolyLys-b-PCL, have been synthesized and characterized. Poly(Lys-g-Glu)-b-PCL has been successfully synthesized where D-gluconolactone was grafted on the NH2 group of PolyLys. These copolymers self-assemble in water to form micelles in the size range 165 to 365 nm and CMC from 0.1 mg/ml to 2 mg/ml. Both micelle size and CMC showed a strong dependency on the hydrophobic chain length. The encapsulation of Ketoprofen and Rifampicin in the different copolymer families was assessed and encapsulation efficiency determined using UV Spectroscopy. The % drug loaded was found to depend on the interaction between drug and copolymer system. Both drugs showed chemical conjugation with PolyLys segment and physical entrapment in the PCL hydrophobic core. Higher encapsulation efficiency was obtained with Rifampicin (17–70%).

Lactic acid bacteria (LAB) were isolated from fresh sugar cane juice. It was found that several isolates exhibited a clear zone and growth on deMan, Rogosa, Sharpe (MRS) agar supplemented with sodium azide, bromocresol purple and sucrose. However, only 17 isolates which formed large yellow areas were selected for further investigations. These isolates were further identified according to their morphological and biochemical characteristics. It was found that 10 of these isolates were homofermenters. One of these 10 isolates was selected for mutagenesis using chemical (Ethidium bromide) and physical (UV-B) mutagens followed by biochemical characterisation. A total of 112 mutants were isolated and 9 homofermentative isolates were further investigated for their ability to produce lactic acid. 1H-NMR spectroscopy confirmed that all mutant isolates produced lactic acid as the sole fermentation product.