Advances in Stimuli-responsive Hydrogels for Tissue Engineering and Regenerative Medicine Applications: A Review Towards Improving Structural Design for 3D Printing.

The physicochemical properties of polymeric hydrogels render them attractive for the development of 3D printed prototypes for tissue engineering in regenerative medicine. Significant effort has been made to design hydrogels with desirable attributes that facilitate 3D printability. In addition, there is significant interest in exploring stimuli-responsive hydrogels to support automated 3D printing into more structurally organised prototypes such as customizable bio-scaffolds for regenerative medicine applications. Synthesizing stimuli-responsive hydrogels is dependent on the type of design and modulation of various polymeric materials to open novel opportunities for applications in biomedicine and bio-engineering. In this review, the salient advances made in the design of stimuli-responsive polymeric hydrogels for 3D printing in tissue engineering are discussed with a specific focus on the different methods of manipulation to develop 3D printed stimuli-responsive polymeric hydrogels. Polymeric functionalisation, nano-enabling and crosslinking are amongst the most common manipulative attributes that affect the assembly and structure of 3D printed bio-scaffolds and their stimuli- responsiveness. The review also provides a concise incursion into the various applications of stimuli to enhance the automated production of structurally organized 3D printed medical prototypes.

A 3D-Printed Biomaterial Scaffold Reinforced with Inorganic Fillers for Bone Tissue Engineering: In Vitro Assessment and In Vivo Animal Studies.

This research aimed to substantiate the potential practicality of utilizing a matrix-like platform, a novel 3D-printed biomaterial scaffold, to enhance and guide host cells' growth for bone tissue regeneration. The 3D biomaterial scaffold was successfully printed using a 3D Bioplotter® (EnvisionTEC, GmBH) and characterized. Osteoblast-like MG63 cells were utilized to culture the novel printed scaffold over a period of 1, 3, and 7 days. Cell adhesion and surface morphology were examined using scanning electron microscopy (SEM) and optical microscopy, while cell viability was determined using MTS assay and cell proliferation was evaluated using a Leica microsystem (Leica MZ10 F). The 3D-printed biomaterial scaffold exhibited essential biomineral trace elements that are significant for biological bone (e.g., Ca-P) and were confirmed through energy-dispersive X-ray (EDX) analysis. The microscopy analyses revealed that the osteoblast-like MG63 cells were attached to the printed scaffold surface. The viability of cultured cells on the control and printed scaffold increased over time (p < 0.05); however, on respective days (1, 3, and 7 days), the viability of cultured cells between the two groups was not significantly different (p > 0.05). The protein (human BMP-7, also known as growth factor) was successfully attached to the surface of the 3D-printed biomaterial scaffold as an initiator of osteogenesis in the site of the induced bone defect. An in vivo study was conducted to substantiate if the novel printed scaffold properties were engineered adequately to mimic the bone regeneration cascade using an induced rabbit critical-sized nasal bone defect. The novel printed scaffold provided a potential pro-regenerative platform, rich in mechanical, topographical, and biological cues to guide and activate host cells toward functional regeneration. The histological studies revealed that there was progress in new bone formation, especially at week 8 of the study, in all induced bone defects. In conclusion, the protein (human BMP-7)-embedded scaffolds showed higher regenerative bone formation potential (week 8 complete) compared to the scaffolds without protein (e.g., growth factor; BMP-7) and the control (empty defect). At 8 weeks postimplantation, protein (BMP-7) significantly promoted osteogenesis as compared to other groups. The scaffold underwent gradual degradation and replacement by new bones at 8 weeks in most defects.

Tannic acid-loaded chitosan-RGD-alginate scaffolds for wound healing and skin regeneration.

Hydrogels have drawn much attention in the field of tissue regeneration and wound healing owing to the application of biocompatible peptides to tailor structural features necessitating optimal tissue remodeling performance. In the current study, polymers and peptide were explored to develop scaffolds for wound healing and skin tissue regeneration. Alginate (Alg), chitosan (CS), and arginine-glycine-aspartate (RGD) were used to fabricate composite scaffolds crosslinked with tannic acid (TA), which also served as a bioactive. The use of RGD transformed the physicochemical and morphological features of the 3D scaffolds and TA crosslinking of the scaffolds improved their mechanical properties, specifically tensile strength, compressive Young's modulus, yield strength, and ultimate compressive strength. The incorporation of TA as both a crosslinker and a bioactive allowed for 86% encapsulation efficiency and burst release of 57% of TA in 24 h, accompanied by an 8.5% steady release per day of up to 90% over 5 d. The scaffolds increased mouse embryonic fibroblast cell viability over 3 d, progressing from slightly cytotoxic to non-cytotoxic (cell viability >90%). Wound closure and tissue regeneration evaluations in a SpragueDawley rat wound model at predetermined wound healing time points highlighted the superiority of the Alg-RGD-CS and Alg-RGD-CS-TA scaffolds over the commercial comparator product and control. The scaffolds' superior performance included accelerated tissue remodeling performance from the early to the late stages of wound healing, indicated by the lack of defects and scarring in scaffold-treated tissues. This promising performance supports the design of wound dressings that can act as delivery systems for the treatment of acute and chronic wounds.

Advances in Polysaccharide- and Synthetic Polymer-Based Vitreous Substitutes.

The vitreous humour is a gel-like structure that composes the majority of each eye. It functions to provide passage of light, be a viscoelastic dampener, and hold the retina in place. Vitreous liquefaction causes retinal detachment and retinal tears requiring pars plana vitrectomy for vitreous substitution. An ideal vitreous substitute should display similar mechanical, chemical, and rheological properties to the natural vitreous. Currently used vitreous substitutes such as silicone oil, perfluorocarbon liquids, and gases cannot be used long-term due to adverse effects such as poor retention time, cytotoxicity, and cataract formation. Long-term, experimental vitreous substitutes composed of natural, modified and synthetic polymers are currently being studied. This review discusses current long- and short-term vitreous substitutes and the disadvantages of these that have highlighted the need for an ideal vitreous substitute. The review subsequently focuses specifically on currently used polysaccharide- and synthetic polymer-based vitreous substitutes, which may be modified or functionalised, or employed as the derivative, and discusses experimental vitreous substitutes in these classes. The advantages and challenges associated with the use of polymeric substitutes are discussed. Innovative approaches to vitreous substitution, namely a novel foldable capsular vitreous body, are presented, as well as future perspectives related to the advancement of this field.

In Situ Forming Chitosan-Alginate Interpolymer Complex Bioplatform for Wound Healing and Regeneration.

Cytocompatibility, biocompatibility, and biodegradability are amongst the most desirable qualities of wound dressings and can be tuned during the bioplatform fabrication steps to enhance wound healing capabilities. A three-stepped approach (partial-crosslinking, freeze-drying, and pulverisation) was employed in fabricating a particulate, partially crosslinked (PC), and transferulic acid (TFA)-loaded chitosan-alginate (CS-Alg) interpolymer complex (IPC) with enhanced wound healing capabilities. The PC TFA-CS-Alg IPC bioplatform displayed fluid uptake of 3102% in 24 h and a stepwise degradation up to 53.5% in 14 days. The PC TFA-CS-Alg bioplatform was used as a bioactive delivery system with an encapsulation efficiency of 65.6%, bioactive loading of 9.4%, burst release of 58.27%, and a steady release of 1.91% per day. PC TFA-CS-Alg displayed a shift in cytocompatibility from slightly cytotoxic (60-90% cell viability) to nontoxic (> 90% cell viability) over a 72-h period in NIH-3T3 cells. The wound closure and histological evaluations of the lesions indicated better wound healing performance in lesions treated with PC TFA-CS-Alg and PC CS-Alg compared to those treated with the commercial product and the control. Application of the particulate bioplatform on the wound via sprinkles, the in situ hydrogel formation under fluid exposure, and the accelerated wound healing performances of the bioplatforms make it a good candidate for bioactive delivery system and skin tissue regeneration.

Linoleic Acid-Based Transferosomes for Topical Ocular Delivery of Cyclosporine A.

Delivering high-molecular-weight hydrophobic peptides, such as cyclosporine A, across the corneal epithelium remains a challenge that is complicated by other physio-anatomical ocular structures that limit the ocular bioavailability of such peptides. Transferosomes have previously been used to improve transdermal permeability, and have the potential for improving the ocular corneal permeability of applicable drugs. In this study, transferosomes for the potential ocular delivery of cyclosporine A were investigated. Linoleic acid was evaluated for its effect on the stability of the transferosomes and was substituted for a portion of the cholesterol in the vesicles. Additionally, Span® 80 and Tween® 80 were evaluated for their effect on transferosome flexibility and toxicity to ocular cells as edge activators. Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy (ATF-FTIR), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) were used to evaluate the physicochemical parameters of the blank and the cyclosporine A-loaded transferosomes. Cyclosporine A release and corneal permeability were studied in vitro and in a New Zealand albino rabbit corneal model, respectively. The linoleic acid contributed to improved stability and the nano-size of the transferosomes. The Tween®-based formulation was preferred on the basis of a more favorable toxicity profile, as the difference in their corneal permeability was not significant. There was an initial burst release of cyclosporine A in the first 24 h that plateaued over one week. The Tween®-based formulation had a flux of 0.78 µg/cm2/h. The prepared transferosomes demonstrated biocompatibility in the ocular cell line, adequately encapsulated cyclosporine A, ensured the corneal permeability of the enclosed drug, and were stable over the period of investigation of 4 months at -20 °C.

Investigation of the 3D Printability of Covalently Cross-Linked Polypeptide-Based Hydrogels.

The 3D printability of poly(l-lysine-ran-l-alanine) and four-arm poly(ethylene glycol) (P(KA)/4-PEG) hydrogels as 3D biomaterial inks was investigated using two approaches to develop P(KA)/4-PEG into 3D biomaterial inks. Only the "composite microgel" inks were 3D printable. In this approach, P(KA)/4-PEG hydrogels were processed into microparticles and incorporated into a polymer solution to produce a composite microgel paste. Polymer solutions composed of either 4-arm PEG-acrylate (4-PEG-Ac), chitosan (CS), or poly(vinyl alcohol) (PVA) were used as the matrix material for the composite paste. The three respective composite microgel inks displayed good 3D printability in terms of extrudability, layer-stacking ability, solidification mechanism, and 3D print fidelity. The biocompatibility of P(KA)/4-PEG hydrogels was retained in the 3D printed scaffolds, and the biofunctionality of bioinert 4-PEG and PVA hydrogels was enhanced. CS-P(KA)/4-PEG inks demonstrated excellent 3D printability and proved highly successful in printing scaffolds with a narrow strand diameter (∼200 µm) and narrow strand spacing (∼500 µm) while the integrity of the vertical and horizontal pores was maintained. Using different needle IDs and strand spacing, certain physical properties of the hydrogels could be tuned, while the 3D printed porosity was kept constant. This included the surface area to volume ratio, the macropore sizes, and the mechanical properties. The scaffolds demonstrated adequate adhesion and spreading of NIH 3T3 fibroblasts seeded on the scaffold surfaces for 4 days. Consequently, the scaffolds were considered suitable for potential applications in wound healing, as well as other soft tissue engineering applications. Apart from the contribution to new 3D biomaterial inks, this work also presented a new and facile method of processing covalently cross-linked hydrogels into 3D printed scaffolds. This could potentially "unlock" the 3D printability of biofunctional hydrogels, which are generally excluded from 3D printing applications.

Evaluation of Composition Effects on the Physicochemical and Biological Properties of Polypeptide-Based Hydrogels for Potential Application in Wound Healing.

In this study, the effect of crosslinking and concentration on the properties of a new library of low-concentration poly(Lys60-ran-Ala40)-based hydrogels for potential application in wound healing was investigated in order to correlate the hydrogel composition with the desired physicochemical and biofunctional properties to expand the assortment of poly-l-lysine (PLL)-based hydrogels suitable for wound healing. Controlled ring-opening polymerization (ROP) and precise hydrogel compositions were used to customize the physicochemical and biofunctional properties of a library of new hydrogels comprising poly(l-lysine-ran-l-alanine) and four-arm poly(ethylene glycol) (P(KA)/4-PEG). The chemical composition and degree of crosslinking via free amine quantification were analyzed for the P(KA)/4-PEG hydrogels. In addition, the rheological properties, pore morphology, swelling behavior and degradation time were characterized. Subsequently, in vitro cell studies for evaluation of the cytotoxicity and cell adhesion were performed. The 4 wt% 1:1 functional molar ratio hydrogel with P(KA) concentrations as low as 0.65 wt% demonstrated low cytotoxicity and desirable cell adhesion towards fibroblasts and thus displayed a desirable combination of properties for wound healing application.

Fabrication and Characterisation of a Photo-Responsive, Injectable Nanosystem for Sustained Delivery of Macromolecules.

The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of ≥80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.

Three-dimensional printing of extracellular matrix (ECM)-mimicking scaffolds: A critical review of the current ECM materials.

The loss of tissues and organs through injury and disease has stimulated the development of therapeutics that have the potential to regenerate and replace the affected tissue. Such therapeutics have the benefit of reducing the reliance and demand for life-saving organ transplants. Of the several regenerative strategies, 3D printing has emerged as the forerunner in regenerative attempts due to the fact that biologically and anatomically correct 3D structures can be fabricated according to the specified need. Despite the progress in this field, improvement is still limited by the difficulty in fabricating scaffolds that adequately mimic the native cellular microenvironment. In response, despite the complexities of the native extracellular matrix (ECM), the inclusion of ECM components into bioinks has emerged as a cutting-edge research area in terms of providing possible ECM-mimicking abilities of the 3D printed constructs. Furthermore, the development of ECM-mimicking scaffolds can potentially assist in improving personalized patient treatments. This review provides a critical analysis of selected naturally occurring ECM components as well as synthetic self-assembling peptides in their ability to provide the required ECM microenvironment for tissue regeneration. The success and possible short comings of each material, as well as the specific characteristics of each bioink, are evaluated.

Carbon Dots as Nanotherapeutics for Biomedical Application.

Carbon nanodots are zero-dimensional spherical allotropes of carbon and are less than 10nm in size (ranging from 2-8nm). Based on their biocompatibility, remarkable water solubility, eco- friendliness, conductivity, desirable optical properties and low toxicity, carbon dots have revolutionized the biomedical field. In addition, they have intrinsic photo-luminesce to facilitate bio-imaging, bio-sensing and theranostics. Carbon dots are also ideal for targeted drug delivery. Through functionalization of their surfaces for attachment of receptor-specific ligands, they ultimately result in improved drug efficacy and a decrease in side-effects. This feature may be ideal for effective chemo-, gene- and antibiotic-therapy. Carbon dots also comply with green chemistry principles with regard to their safe, rapid and eco-friendly synthesis. Carbon dots thus, have significantly enhanced drug delivery and exhibit much promise for future biomedical applications. The purpose of this review is to elucidate the various applications of carbon dots in biomedical fields. In doing so, this review highlights the synthesis, surface functionalization and applicability of biodegradable polymers for the synthesis of carbon dots. It further highlights a myriad of biodegradable, biocompatible and cost-effective polymers that can be utilized for the fabrication of carbon dots. The limitations of these polymers are illustrated as well. Additionally, this review discusses the application of carbon dots in theranostics, chemo-sensing and targeted drug delivery systems. This review also serves to discuss the various properties of carbon dots which allow chemotherapy and gene therapy to be safer and more target-specific, resulting in the reduction of side effects experienced by patients and also the overall increase in patient compliance and quality of life.

Hydrogel Biomaterials for Application in Ocular Drug Delivery.

There are many challenges involved in ocular drug delivery. These are a result of the many tissue barriers and defense mechanisms that are present with the eye; such as the cornea, conjunctiva, the blinking reflex, and nasolacrimal drainage system. This leads to many of the conventional ophthalmic preparations, such as eye drops, having low bioavailability profiles, rapid removal from the administration site, and thus ineffective delivery of drugs. Hydrogels have been investigated as a delivery system which is able to overcome some of these challenges. These have been formulated as standalone systems or with the incorporation of other technologies such as nanoparticles. Hydrogels are able to be formulated in such a way that they are able to change from a liquid to gel as a response to a stimulus; known as "smart" or stimuli-responsive biotechnology platforms. Various different stimuli-responsive hydrogel systems are discussed in this article. Hydrogel drug delivery systems are able to be formulated from both synthetic and natural polymers, known as biopolymers. This review focuses on the formulations which incorporate biopolymers. These polymers have a number of benefits such as the fact that they are biodegradable, biocompatible, and non-cytotoxic. The biocompatibility of the polymers is essential for ocular drug delivery systems because the eye is an extremely sensitive organ which is known as an immune privileged site.

Bioplatform Fabrication Approaches Affecting Chitosan-Based Interpolymer Complex Properties and Performance as Wound Dressings.

Chitosan can form interpolymer complexes (IPCs) with anionic polymers to form biomedical platforms (BMPs) for wound dressing/healing applications. This has resulted in its application in various BMPs such as gauze, nano/microparticles, hydrogels, scaffolds, and films. Notably, wound healing has been highlighted as a noteworthy application due to the remarkable physical, chemical, and mechanical properties enabled though the interaction of these polyelectrolytes. The interaction of chitosan and anionic polymers can improve the properties and performance of BMPs. To this end, the approaches employed in fabricating wound dressings was evaluated for their effect on the property-performance factors contributing to BMP suitability in wound dressing. The use of chitosan in wound dressing applications has had much attention due to its compatible biological properties. Recent advancement includes the control of the degree of crosslinking and incorporation of bioactives in an attempt to enhance the physicochemical and physicomechanical properties of wound dressing BMPs. A critical issue with polyelectrolyte-based BMPs is that their effective translation to wound dressing platforms has yet to be realised due to the unmet challenges faced when mimicking the complex and dynamic wound environment. Novel BMPs stemming from the IPCs of chitosan are discussed in this review to offer new insight into the tailoring of physical, chemical, and mechanical properties via fabrication approaches to develop effective wound dressing candidates. These BMPs may pave the way to new therapeutic developments for improved patient outcomes.

Multifunctional Magnetic Nanowires: Design, Fabrication, and Future Prospects as Cancer Therapeutics.

Traditional cancer therapeutics are limited by factors such as multi-drug resistance and a plethora of adverse effect. These limitations need to be overcome for the progression of cancer treatment. In order to overcome these limitations, multifunctional nanosystems have recently been introduced into the market. The employment of multifunctional nanosystems provide for the enhancement of treatment efficacy and therapeutic effect as well as a decrease in drug toxicity. However, in addition to these effects, magnetic nanowires bring specific advantages over traditional nanoparticles in multifunctional systems in terms of the formulation and application into a therapeutic system. The most significant of which is its larger surface area, larger net magnetic moment compared to nanoparticles, and interaction under a magnetic field. This results in magnetic nanowires producing a greater drug delivery and therapeutic platform with specific regard to magnetic drug targeting, magnetic hyperthermia, and magnetic actuation. This, in turn, increases the potential of magnetic nanowires for decreasing adverse effects and improving patient therapeutic outcomes. This review focuses on the design, fabrication, and future potential of multifunctional magnetic nanowire systems with the emphasis on improving patient chemotherapeutic outcomes.

The Hemocompatibility of Nanoparticles: A Review of Cell-Nanoparticle Interactions and Hemostasis.

Understanding cell-nanoparticle interactions is critical to developing effective nanosized drug delivery systems. Nanoparticles have already advanced the treatment of several challenging conditions including cancer and human immunodeficiency virus (HIV), yet still hold the potential to improve drug delivery to elusive target sites. Even though most nanoparticles will encounter blood at a certain stage of their transport through the body, the interactions between nanoparticles and blood cells is still poorly understood and the importance of evaluating nanoparticle hemocompatibility is vastly understated. In contrast to most review articles that look at the interference of nanoparticles with the intricate coagulation cascade, this review will explore nanoparticle hemocompatibility from a cellular angle. The most important functions of the three cellular components of blood, namely erythrocytes, platelets and leukocytes, in hemostasis are highlighted. The potential deleterious effects that nanoparticles can have on these cells are discussed and insight is provided into some of the complex mechanisms involved in nanoparticle-blood cell interactions. Throughout the review, emphasis is placed on the importance of undertaking thorough, all-inclusive hemocompatibility studies on newly engineered nanoparticles to facilitate their translation into clinical application.

Design and characterisation of PHBV-magnesium oleate directional nanofibers for neurosupport.

The focus of significance in neuronal repair strategies is the design of scaffold systems capable of promoting neuronal regeneration and directional guidance via provision of a biomimetic environment resemblance of native neural tissue. The purpose of this study was to synthesize triple-cue electrospun aligned nanofibrous films (physical cue) of poly(3-hyroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) blended with magnesium-oleate (MgOl) (chemical cue) and N-acetyl-L-cysteine (NAC) (therapeutic cue) with potential incorporation into hollow nerve guidance conduits for an enhanced regenerative strategy. A Box-Behnken experimental design of 15 formulations, were analysed for crystallinity, textural properties and in vitro water-uptake, erosion, NAC-release and PC12 cell viability. Nucleating effects of MgOl provided tuning of PHBV electrospinning-induced crystallinity and mechanical properties. Tensile strengths and deformation moduli of ±12 MPa and ±7 MP, respectively, were attainable, thereby matching native nerve mechanics. Crystallinity changes ascribed differing release kinetics to NAC over 30 d: diffusion-based (42%-58% crystallinity with 33%-47% fractional release) and polymer-relaxational (59%-65% crystallinity with 60%-82% fractional release). The synergistic activity of MgOl and NAC increased PC12 proliferation by 32.6% compared to the control. MgOl produced dual actions as non-toxic plasticiser and PC12 cell proliferation-promoter via nucleation and neurotrophic-like effects, respectively. Controlled release of NAC imparted neuro-protectant effects on PC12 cells and promoted neurite extension, thus, making electrospun PHBV-MgOl nanofibrous films a versatile and promising approach for axonal guidance in peripheral nerve repair strategies.

Folate-decorated, endostatin-loaded, nanoparticles for anti-proliferative chemotherapy in esophaegeal squamous cell carcinoma.

This study aims to design and synthesize Endostatin (ENT)-loaded nanoparticles using Folic acid (FA) as a driver for targeted anti-proliferative chemotherapy in Esophageal Squamous Cell Carcinoma (ESCC). An ionic gelation method was employed to formulate FA-decorated, ENT-loaded nanoparticles, which were tested in vitro on KYSE-30 cells using unbiased stereological approaches. FA-ENT nanoparticles were internalized into ESCC cells with preferential binging to the nucleus and mitochondria for necrotic and apoptotic effects. Nanoparticles showed increased proliferation inhibition of 64.71% and reduced KYSE-30 cell migration of up to 74.12% when compared to the control. Positively charged spherical nanoparticles, with selective pH responsive ENT release, were further tested in vivo employing a tumor xenograft model. Tumor mass increased up to 5505.54 mm3 in the control group while a substantial reduction occurred in the treatment group (native ENT, ENT-nano and FA-ENT-nano) down to 128.23 mm3 (97.67%). Tumor volume was reduced from 1000.2 mm3 to 567.64 mm3 (43.25%) in the native ENT group, from 324.43 mm3 to 190.25 mm3 (41.36%) in ENT-nano group (non-targeted system), and from 1374.21 mm3 to 998.67 mm3 (27.33%) in FA-ENT-nano group (targeted system) following treatment. There were no significant differences in the body weight of mice treated with the nano-formulations as opposed to the control mice. FA-decorated nanoparticles for active transport of ENT into tumor cells with an enhanced in vitro and in vivo anti-proliferative efficacy in ESCC therapy were synthesized.

Advances in Biodegradable Nano-Sized Polymer-Based Ocular Drug Delivery.

The effective delivery of drugs to the eye remains a challenge. The eye has a myriad of defense systems and physiological barriers that leaves ocular drug delivery systems with low bioavailability profiles. This is mainly due to poor permeability through the epithelia and rapid clearance from the eye following administration. However, recent advances in both polymeric drug delivery and biomedical nanotechnology have allowed for improvements to be made in the treatment of ocular conditions. The employment of biodegradable polymers in ocular formulations has led to improved retention time, greater bioavailability and controlled release through mucoadhesion to the epithelia in the eye, amongst other beneficial properties. Nanotechnology has been largely investigated for uses in the medical field, ranging from diagnosis of disease to treatment. The nanoscale of these developing drug delivery systems has helped to improve the penetration of drugs through the various ocular barriers, thus improving bioavailability. This review will highlight the physiological barriers encountered in the eye, current conventional treatment methods as well as how polymeric drug delivery and nanotechnology can be employed to optimize drug penetration to both the anterior and posterior segment of the eye.

Development of a fluid-absorptive alginate-chitosan bioplatform for potential application as a wound dressing.

This study introduces a novel approach in fabricating bioplatforms with favourable physical, chemical, and mechanical properties for wound dressing applications. The approach employs a three-step method; partial-crosslinking of polymers into soft macromatrices, lyophilization, and pulverization of those macromatrices to obtain polymer particles with improved properties. For investigation of this approach, the ionic polysaccharides, sodium alginate and chitosan were partially crosslinked with calcium chloride and sodium tripolyphosphate, respectively, followed by interpolymer complexation (IPC) for formation of the bioplatform. The formulations displayed good thermal stability with enhanced water uptake. The IPC exhibited water uptake of 4343.4% over 24 h and displayed 78% biodegradation over 14 days, which was superior to that of a commercial alginate-based wound dressing (1612.56% swelling and 16.26% biodegradation). The bioplatform thus possessed promising fluid-absorptivity and biodegradability, for potential application as a wound therapeutic system.

Preprocessing of Medical Image Data for Three-Dimensional Bioprinted Customized-Neural-Scaffolds.

IMPACT STATEMENT: Nerve damage, which can be devastating, triggers several biological cascades, which result in the insufficiencies of the human nervous system to provide complete nerve repair and regain of function. Since no therapeutic strategy exists to provide immediate attention and intervention to patients with newly acquired nerve damage, we propose a strategy in which accelerated medical image processing through graphical processing unit implementation and three-dimensional printing are combined to produce a time-efficient, patient-specific (custom-neural-scaffold) solution to nerve damage. This work aims to beneficially shorten the time required for medical decision-making so that improved patient outcomes are achieved.