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The chemical constituents of Psidium guajava essential oil was analyzed by using Gas Chromatography-Mass Spectrometry. The essential oil was obtained from dried leaves by hydrodistillation method using a Clevenger apparatus. From the initial screening, 20 components were detected with different amounts traced. The most abundant constituents observed in the oil were Limonene (23.39%), Caryophyllene (18.19%), Cyclooctasiloxane (14.46%), and Pinene (13.50%). The essential oil showed significant antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis and Bacillus cereus with inhibition range of 6-25 mm. The profile of chemical constituents present in the oil able to serve as preliminary screening of the bioactive components posses in a natural plants for investigating antibacterial properties in regenerative medicine.

Cellulose as a renewable material has received enormous interest in recent time with an effort to minimize the environmental load from mining earthborn functional materials as well as reducing carbon footprint. This work demonstrates that high quality cellulose could be produced from empty fruit bunch of oil palm plantation and could be developed into nanofibers. A small amount of poly (ε-caprolactone) (PCL) was added to the EFB driven cellulose acetate (CA) to develop them as nanofibers by electrospinning technique; this composition was further enhanced by adding curcumin, which is a natural anti-inflammatory, and compared their morphology, structure, mechanical and surface properties.

Liver/hepatocyte regeneration effectively occurs after an in vivo physiological insult and is guided by stimuli from the extracellular matrix (ECM) and signals from neighbouring cells. However, in spite of its ability to regenerate in vivo, long-term propagation of liver cells in culture has been a formidable task. This is largely because we still do not have ideal biomaterials that can recapitulate all the essential properties of a native liver ECM ex vivo. Nonetheless, many biomaterials based on natural and synthetic polymers and their blends have been developed in recent years for supporting hepatocyte cultures. Use of decellularized native liver ECM represents one vital step towards liver tissue engineering; however, native ECM has to be appropriately amended with other biomaterials. This critical review presents succinct details about the multitude of biomaterials that have been investigated over the past few years and also propose advanced options for future endeavours in hepatic tissue engineering.

Far-flung evolution in tissue engineering enabled the development of bioactive and biodegradable materials to generate biocomposite nanofibrous scaffolds for bone repair and replacement therapies. Polymeric bioactive nanofibers are to biomimic the native extracellular matrix (ECM), delivering tremendous regenerative potentials for drug delivery and tissue engineering applications. It's been known from few decades that Zinc oxide (ZnO) nanoparticles are enhancing bone growth and providing proliferation of osteoblasts when incorporated with hydroxyapatite (HAp). We attempted to investigate the interaction between the human foetal osteoblasts (hFOB) with ZnO doped HAp incorporated biocomposite poly(L-lactic acid)-co-poly(ε-caprolactone) and silk fibroin (PLACL/SF) nanofibrous scaffolds for osteoblasts mineralization in bone tissue regeneration. The present study, we doped ZnO with HAp (ZnO(HAp) using the sol-gel ethanol condensation technique. The properties of PLACL/SF/ZnO(HAp) biocomposite nanofibrous scaffolds enhanced with doped and blended ZnO/HAp were characterized using Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Contact angle and Tensile studies to determine the morphology, functionality, wettability and stability. The in vitro study results showed that the addition of ZnO and HAp enhances the secretion of bone mineral matrix (98%) with smaller fiber diameter (139.4 ± 27 nm) due to the presence of silk fibroin showing potential tensile properties (322.4%), and increased the proliferation of osteoblasts for bone tissue regeneration.

This article demonstrates the development of nanofibrous cloths by electrospinning of renewable materials, i.e., curcumin-loaded 90% cellulose acetate (CA)/10% poly(ε-caprolactone) (PCL), for applications in regenerative medicine. The CA is derived from the biomass waste of the oil palm plantation (empty fruit bunch). The nanofiber scaffolds are characterized for the fiber morphology, microstructure, thermal properties, and wettability. The optimized smooth and bead-free electrospun fiber cloth contains 90% CA and 10% PCL in two curcumin compositions (0.5 and 1 wt%). The role of curcumin is shown to be two-fold: the first is its function as a drug and the second is its role in lowering the water contact angle and increasing the hydrophilicity. The hydrophilicity enhancements are related to the hydrogen bonding between the components. The enhanced hydrophilicity contributed to improve the swelling behavior of the scaffolds; the CA/PCL/Cur (0.5%) and the CA/PCL/Cur (1.0%) showed swelling of ~700 and 950%, respectively, in phosphate-buffered saline (PBS). The drug-release studies revealed the highest cumulative drug release of 60% and 78% for CA/PCL/Cur (0.5%) and CA/PCL/Cur (1.0%) nanofibers, respectively. The in-vitro studies showed that CA/PCL/Cur (0.5 wt%) and CA/PCL/Cur (1.0 wt%) nanofiber scaffolds facilitate a higher proliferation and expression of actin in fibroblasts than those scaffolds without curcumin for wound healing applications.

Tissue engineering makes use of the principles of medicine, biology and engineering and integrates them into the design of biological substitutes to restore, maintain and improve the functions of tissue. To fabricate a functional tissue, the engineered structures have to be able to mimic the extracellular matrix (ECM), provide the tissue with oxygen and nutrient circulation as well as remove metabolic wastes in the period of tissue regeneration. Continued efforts have been made in order to fabricate advanced functional three-dimensional scaffolds for tissue engineering. Electrospinning has been recognized and served as one of the most useful techniques based on the resemblance between electrospun fibers and the native tissues. Over the past few decades, a bewildering variety of nanofibrous scaffolds have been developed for various biomedical applications, such as tissue regeneration and therapeutic agent delivery. The present review aims to provide with researchers an in-depth understanding of the promising role and the practical region of applicability of electrospinning in tissue engineering and regenerative medicine by highlighting the outcomes of the most recent studies performed in this field. We address the current strategies used for improving the physicochemical interactions between the cells and the nanofibrous surface. We also discuss the progress and challenges associated with the use of electrospinning for tissue engineering and regenerative medicine applications.

Currently, pharmaceutical research is directed wide range for developing new drugs for oral administration to target disease. Acyclovir formulation is having common issues of short half-life and poor permeability, causing messy treatment which results in patient incompliance. The present study formulates a lipid polymeric hybrid nanoparticles for antiviral acyclovir (ACV) agent with Phospholipon® 90G (lecithin), chitosan, and polyethylene glycol (PEG) to improve controlled release of the drugs. The study focused on the encapsulation of the ACV in lipid polymeric particle and their sustained delivery. The formulation developed for the self-assembly of chitosan and lecithin to form a shell encapsulating acyclovir, followed by PEGylation. Optimisation was performed via Box-Behnken Design (BBD), forming nanoparticles with size of 187.7 ± 3.75 nm, 83.81 ± 1.93% drug-entrapped efficiency (EE), and + 37.7 ± 1.16 mV zeta potential. Scanning electron microscopy and transmission electron microscopy images displayed spherical nanoparticles formation. Encapsulation of ACV and complexity with other physical parameters are confirmed through analysis using Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. Nanoparticle produced was capable of achieving 24-h sustained release in vitro on gastric and intestinal environments. Ex vivo study proved the improvement of acyclovir’s apparent permeability from 2 × 10−6 to 6.46 × 10−6 cm s−1. Acyclovir new formulation was achieved to be stable up to 60 days for controlled release of the drugs. Graphical abstract

Mesenchymal stem cell (MSC)-based liver tissue engineering on nanofibrous scaffold holds great promise for cell-based therapy in liver injuries and end-stage liver failure treatments. We investigated the hepatic trans-differentiation potential of human MSCs on a biocomposite poly(l-lactic acid)-co-poly (?-caprolactone)/collagen (PLACL/collagen) nanofibrous scaffold. The nanofibrous scaffolds comprised of PLACL, collagen and a PLACL/collagen blend (2:1) were fabricated by electrospinning and also evaluated for fiber morphology, surface wettability, functional groups, porosity and tensile properties. Hepatic trans-differentiation of human bone marrow-derived MSCs (hMSCs) was carried out on these scaffolds over a period of 28 days using sequential induction with hepatogenic growth factors. Hepatogenesis was confirmed by scanning electron microscopy (SEM), cell phenotype tracking dye expression, quantitative expression of hepatic genes, immunofluorescence staining of hepatocyte-specific markers and albumin release. The results proved that the porous PLACL/collagen nanofibrous scaffold supported enhanced hMSC proliferation and hepatic trans-differentiation compared to individual PLACL and collagen scaffolds as well as a monolayer culture on tissue culture plate (TCP). Interestingly, hMSC-derived hepatocyte-like cells on PLACL/collagen nanofibrous scaffolds could aggregate to form functional 'hepatospheres' similar to normal hepatic spheroids. The present study concludes that PLACL/collagen nanofibrous scaffolds are potentially biomimetic and upon sequential induction with hepatogenic growth factors/cytokines, it augments trans-differentiation of hMSCs towards functional hepatosphere formation. Such bioengineered nanofibrous scaffold hepatic construct provides a promising approach for cellular therapy of damaged livers in end-stage liver failure treatments. � The Royal Society of Chemistry.

Nanofibers play a significant role in tissue engineering and drug delivery because of the ease with which drugs or pharmaceuticals may be incorporated into the nano-formulation. Natural protein nanofibers are cross-linked (CXLed) employing a new protocol to improve their stability for perspective usage as tissue engineering or drug delivery scaffolds. The protocol utilizes a non-toxic, natural material vitamin based CXL protocol that works well for stabilizing protein nanofibers. We have tested the generation of reactive oxygen species (ROS) from UV treated riboflavin-gelatin microfibers, film or solution that helps in gelatin (Gel) CXLing and results in improved mechanical properties. Further natural proteins Gel and fibrinogen (Fib) solutions were also CXLed using vitamin B2 (riboflavin (Rib)) released from Rib-loaded polycaprolactone (PCL) nanofibers followed by UV treatment. The sustained release of Rib from PCL nanofibers is studied with in vitro drug release experiments and in vitro hydrogel formation upon treatment with the natural protein solutions. Rib-loaded nanofibers were characterized with SEM and AFM for morphology, mechanical strength calculation and FT-IR for ensuring drug incorporation. The Rib encapsulation in the nanofiber reservoirs enables the sustained release, and the ROS generating nanofibers could find application as a patch for CXLing any protein fiber or fibrous tissue, such as ocular, skin or cardiac tissue engineering.

A biomimetic Zein polydopamine based nanofiber scaffold was fabricated to deliver bone morphogenic protein-2 (BMP-2) peptide conjugated titanium dioxide nanoparticles in a sustained manner for investigating its osteogenic differentiation potential. To prolong its retention time at the target site, BMP-2 peptide has been conjugated to titanium dioxide nanoparticles owing to its high surface to volume ratio. The effect of biochemical cues from BMP-2 peptide and nanotopographical stimulation of electrospun Zein polydopamine nanofiber were examined for its enhanced osteogenic expression of human fetal osteoblast cells. The sustained delivery of bioactive signals, improved cell adhesion, mineralization, and differentiation could be attributed to its highly interconnected nanofibrous matrix with unique material composition. Further, the expression of osteogenic markers revealed that the fabricated nanofibrous scaffold possess better cell-biomaterial interactions. These promising results demonstrate the potential of the composite nanofibrous scaffold as an effective biomaterial substrate for bone regeneration.

Skin is a very complex organ and hence designing a bioengineered skin model replicating the essential physiological characteristics for replacing the diseased or damaged parts has been a challenging goal for many. Newer technologies for satisfying most of the criteria are being attempted with the copious efforts of biologists, engineers, physiologists, using multitude of features in combination. Amongst them nanotechnology based biomaterials have gained prominence owing to the enhanced pharmacokinetics, bio-distribution profile, extended half-life and reduced side effects. Designing a matrix that can be assimilated into the body during the regeneration and delivering the essential pharmacological agents in a temporal and spatially specific manner is a tremendous goal. This review essentially deals with the various approaches for designing a multidisciplinary translational smart matrix for addressing the various skin related ailments.

Bone disorders are the most common cause of severe long term pain and physical disability, and affect millions of people around the world. In the present study, we report bio-inspired preparation of bone-like composite structures by electrospinning of collagen containing catecholamines and Ca(2+). The presence of divalent cation induces simultaneous partial oxidative polymerization of catecholamines and crosslinking of collagen nanofibers, thus producing mats that are mechanically robust and confer photoluminescence properties. Subsequent mineralization of the mats by ammonium carbonate leads to complete oxidative polymerization of catecholamines and precipitation of amorphous CaCO3. The collagen composite scaffolds display outstanding mechanical properties with Young's modulus approaching the limits of cancellous bone. Biological studies demonstrate that human fetal osteoblasts seeded on to the composite scaffolds display enhanced cell adhesion, penetration, proliferation, differentiation and osteogenic expression of osteocalcin, osteopontin and bone matrix protein when compared to pristine collagen or tissue culture plates. Among the two catecholamines, mats containing norepinephrine displayed superior mechanical, photoluminescence and biological properties than mats loaded with dopamine. These smart multifunctional scaffolds could potentially be utilized to repair and regenerate bone defects and injuries.

Transdermal drug delivery using microneedles is increasingly gaining interest due to the issues associated with oral drug delivery routes. Gastrointestinal route exposes the drug to acid and enzymes present in the stomach, leading to denaturation of the compound and resulting in poor bioavailability. Microneedle transdermal drug delivery addresses the problems linked to oral delivery and to relieves the discomfort of patients associated with injections to increase patient compliance. Microneedles can be broadly classified into five types: solid microneedles, coated microneedles, dissolving microneedles, hollow microneedles, and hydrogel-forming microneedles. The materials used for the preparation of microneedles dictate the different applications and features present in the microneedle. Polymeric microneedle arrays present an improved method for transdermal administration of drugs as they penetrate the skin stratum corneum barrier with minimal invasiveness. The review summarizes the importance of polymeric microneedle and discussed some of the most important therapeutic drugs in research, mainly protein drugs, vaccines and small molecule drugs in regenerative medicine.

Chetna Dhand,1,2,* Yamini Balakrishnan,3,* Seow Theng Ong,4,* Neeraj Dwivedi,5 Jayarama R Venugopal,6 Sriram Harini,1 Chak Ming Leung,3 Kenny Zhi Wei Low,7 Xian Jun Loh,7 Roger W Beuerman,1,2 Seeram Ramakrishna,8 Navin Kumar Verma,1,4 Rajamani Lakshminarayanan1,2 1Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Discovery Tower, Singapore; 2Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore; 3Department of Bioengineering, National University of Singapore, Singapore; 4Dermatology and Skin Biology, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 5Department of Electrical and Computer Engineering, National University of Singapore, Singapore; 6Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Gambang, Malaysia; 7Department of Mechanical Engineering, Faculty of Engineering, Center for Nanofibers and Nanotechnology, National University of Singapore, Singapore; 8Soft Materials Department, Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research, Singapore *These authors contributed equally tothiswork Introduction: In search for cross-linkers with multifunctional characteristics, the present work investigated the utility of quaternaryammonium organosilane (QOS) as a potential cross-linker for electrospun collagen nanofibers. We hypothesized that the quaternary ammonium ions improve the electrospinnability by reducing the surface tension and confer antimicrobial properties, while the formation of siloxane after alkaline hydrolysis could cross-link collagen and stimulate cell proliferation. Materials and methods: QOScollagen nanofibers were electrospun by incorporating various concentrations of QOS (0.1%–10% w/w) and were cross-linked in situ after exposure to ammonium carbonate. The QOS cross-linked scaffolds were characterized and their biological properties were evaluated in terms of their biocompatibility, cellular adhesion and metabolic activity for primary human dermal fibroblasts and human fetal osteoblasts. Results and discussion: The study revealed that 1) QOS cross-linking increased the flexibility of otherwise rigid collagen nanofibers and improved the thermal stability; 2) QOS cross-linked mats displayed potent antibacterial activity and 3) the biocompatibility of the composite mats depended on the amount of QOS present in dope solution – at low QOS concentrations (0.1% w/w), the mats promoted mammalian cell proliferation and growth, whereas at higher QOS concentrations, cytotoxic effect was observed. Conclusion: This study demonstrates that QOS cross-linked mats possess anti-infective properties and confer niches for cellular growth and proliferation, thus offering a useful approach, which is important for hard and soft tissue engineering and regenerative medicine. Keywords: anti-infective wound dressing, cyto-compatible nanofibre, electrospinning, cost-effective cross-linker, tissue regeneration, antimicrobial

The use of herbal medicines is a common practice around the world since ancient times. The recent advancement in the field of phytochemical and phytopharmacological sciences has helped to elucidate the composition and biological activities of several medicinal plant products. The active component of most of the medicinal plants is water soluble but has a low absorption, because they are unable to cross the lipid membranes of the cells, have an excessively high molecular size, or are poorly absorbed, resulting in loss of bioavailability and efficacy. One of the novel approaches to overcome these disadvantages is the use of nanotechnology. The process helps to increase the bioavailability and also to cross various biological barriers because of the size range. The nanosystems can deliver the active constituent at any particular concentration during the entire treatment period and also helps in directing it to the desired site of action. Conventional treatments do not meet these requirements. This review gives overall information about the commonly used natural medicine and the nanotechnology-based drug delivery systems.

Development of bioengineered scaffolds for bone tissue regeneration is a growing area of research, especially those involving biodegradable electrospun nanofibers incorporated with ceramic nanoparticles, since they can mimic the extracellular matrix (ECM) of the native bone. In the current study, a biocomposite nanofibrous scaffolds consisting of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), fibrinogen (FIB) and bredigite (BR) nanoparticles was fabricated through electrospinning. The morphological, chemical and mechanical characteristics of the resultant scaffolds were studied by using field emission-scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR) and tensile tester, respectively. It was found that PHBV-FIB-BR scaffolds exhibited enhanced tensile strength and young modulus compared to PHBV and PHBV-FIB scaffolds. In addition, the measurements of the water contact angle suggested that incorporation of bredigite and fibrinogen into PHBV could improve the hydrophilicity of the composites. The results of bioactivity assessment performed in the simulated body fluid (SBF) demonstrated that the presence of the bredigite nanoparticles induced the nucleation and growth of apatite layer on the surface of PHBV-FIB-BR scaffold in SBF. Furthermore, the ion concentration changes of SBF solutions with composite scaffolds showed that PHBV-FIB-BR scaffolds released Ca and Si ions, which can stimulate osteoblast proliferation. The results of cell culture studies revealed the higher osteoblast proliferation, mineralization and differentiation on PHBV-FIB-BR and PHBV-FIB scaffolds than on PHBV. Our results suggest that PHBV-FIB-BR nanofibrous scaffold would be a promising candidate as a biocomposite nanofibrous scaffold material for tissue engineering applications.Development of bioengineered scaffolds for bone tissue regeneration is a growing area of research, especially those involving biodegradable electrospun nanofibers incorporated with ceramic nanoparticles, since they can mimic the extracellular matrix (ECM) of the native bone. In the current study, a biocomposite nanofibrous scaffolds consisting of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), fibrinogen (FIB) and bredigite (BR) nanoparticles was fabricated through electrospinning. The morphological, chemical and mechanical characteristics of the resultant scaffolds were studied by using field emission-scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR) and tensile tester, respectively. It was found that PHBV-FIB-BR scaffolds exhibited enhanced tensile strength and young modulus compared to PHBV and PHBV-FIB scaffolds. In addition, the measurements of the water contact angle suggested that incorporation of bredigite and fibrinogen into PHBV could improve the hydrophi...

Generating porous topographic substrates, by mimicking the native extracellular matrix (ECM) to promote the regeneration of damaged bone tissues, is a challenging process. Generally, scaffolds developed for bone tissue regeneration support bone cell growth and induce bone-forming cells by natural proteins and growth factors. Limitations are often associated with these approaches such as improper scaffold stability, and insufficient cell adhesion, proliferation, differentiation, and mineralization with less growth factor expression. Therefore, the use of engineered nanoparticles has been rapidly increasing in bone tissue engineering (BTE) applications. The electrospray technique is advantageous over other conventional methods as it generates nanomaterials of particle sizes in the micro/nanoscale range. The size and charge of the particles are controlled by regulating the polymer solution flow rate and electric voltage. The unique properties of nanoparticles such as large surface area-to-volume ratio, small size, and higher reactivity make them promising candidates in the field of biomedical engineering. These nanomaterials are extensively used as therapeutic agents and for drug delivery, mimicking ECM, and restoring and improving the functions of damaged organs. The controlled and sustained release of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides from nanoparticles has been well developed in nanomedicine. This review provides an insight into the preparation of nanoparticles by electrospraying technique and illustrates the use of nanoparticles in drug delivery for promoting bone tissue regeneration. MOE (Min. of Education, S’pore) Accepted version

Cardiac tissue engineering promises to revolutionize the treatment of patients with end-stage heart failure and provide new solutions to the serious problems of shortage of heart donors. The influence of extracellular matrix (ECM) plays an influential role along with nanostructured components for guided stem cell differentiation. Hence, nanoparticle embedded Nanofibrous scaffolds of FDA approved polycaprolactone (PCL), Vitamin B12 (Vit B12), Aloe Vera(AV) and Silk fibroin(SF) was constructed to differentiate mesenchymal stem cells into cardiac lineage. Cardiomyocytes (CM) and Mesenchymal stem cells (MSC) were co-cultured on these fabricated nanofibrous scaffolds for the regeneration of infarcted myocardium. Results demonstrated that synthesized gold nanoparticles were of the size 16 nm and the nanoparticle loaded nanofibrous scaffold has a mechanical strength of 2.56 MPa matching that of the native myocardium. The gold nanoparticle blended PCL scaffolds were found to be enhancing the MSCs proliferation and differentiation into cardiogenesis. Most importantly the phenotype and cardiac marker expression in differentiated MSCs were highly resonated in gold nanoparticle loaded nanofibrous scaffolds. The appropriate mechanical strength provided by the functionalized nanofibrous scaffolds profoundly supported MSCs to produce contractile proteins and achieve typical cardiac phenotype.

Advances in tissue engineering have enabled the development of bioactive composite materials to generate biomimetic nanofibrous scaffolds for bone replacement therapies. Polymeric biocomposite nanofibrous scaffolds architecturally mimic the native extracellular matrix (ECM), delivering tremendous regenerative potential for bone tissue engineering. In the present study, biocompatible poly(l-lactic acid)-co-poly(e-caprolactone)-silk fibroin-hydroxyapatite-hyaluronic acid (PLACL-SF-HaP-HA) nanofibrous scaffolds were fabricated by electrospinning to mimic the native ECM. The developed nanofibrous scaffolds were characterized in terms of fibre morphology, functional group, hydrophilicity and mechanical strength, using SEM, FTIR, contact angle and tabletop tensile-tester, respectively. The nanofibrous scaffolds showed a higher level of pore size and increased porosity of up to 95% for the exchange of nutrients and metabolic wastes. The fibre diameters obtained were in the range of around 255 ± 13.4-789 ± 22.41 nm. Osteoblasts cultured on PLACL-SF-HaP-HA showed a significantly (p < 0.001) higher level of proliferation (53%) and increased osteogenic differentiation and mineralization (63%) for the inclusion of bioactive molecules SF-HA. Energy-dispersive X-ray analysis (EDX) data proved that the presence of calcium and phosphorous in PLACL-SF-HaP-HA nanofibrous scaffolds was greater than in the other nanofibrous scaffolds with cultured osteoblasts. The obtained results for functionalized PLACL-SF-HaP-HA nanofibrous scaffolds proved them to be a potential biocomposite for bone tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.

Two-dimensional scaffolds, three-dimensional scaffolds, and dermal substitutes are extensively used for biomedical applications in skin tissue regeneration. Not much explored synthetic polymers, like poly(l-lactic acid)-co-poly-(e-caprolactone) (PLACL), natural polymers, like silk fibroin (SF), and active inducing agents, such as ascorbic acid (AA) and tetracycline hydrochloride (TCH), represent a favorable matrix for fabricating dermal substitutes to engineer artificial skin for wound repair. The profligate nature of residing skin cells near the wound site is a paramount to survival and also regulating stem cells and other cellular networks and mechanical forces. PLACL/SF/TCH/AA nanofibrous scaffolds were fabricated by electrospinning and characterized for fiber morphology, membrane porosity, wettability, and significant subchains using Fourier transform infrared spectroscopy for culturing human-derived dermal fibroblasts. The PLACL, PLACL/SF, PLACL/SF/TCH, and PLACL/SF/TCH/AA scaffolds obtained diameters between 250 and 340 nm. The secretion of collagen by the laboratory-grown fibroblasts over the AA-blended scaffolds was found to be significantly higher compared with that of other scaffolds. The obtained results positively prove that introduction of naturally secreting compounds (AA) by the cells into the nanofibrous scaffolds will favor cell's microenvironment and eventually leads to complete tissue regeneration.

Mimicking native extracellular matrix with electrospun porous bio-composite nanofibrous scaffolds has huge potential in bone tissue regeneration. The aim of this study is to fabricate porous poly(l-lactic acid)-co-poly-(ε-caprolactone)/silk fibroin/ascorbic acid/tetracycline hydrochloride (PLACL/SF/AA/TC) and nanohydroxyapatite (n-HA) was deposited by calcium-phosphate dipping method for bone tissue engineering (BTE). Fabricated nanofibrous scaffolds were characterized for fiber morphology, hydrophilicity, porosity, mechanical test and chemical properties by FT-IR and EDX analysis. The results showed that the fiber diameter and pore size of scaffolds observed around 228±62-320±22nm and 1.5-6.9μm respectively. Resulting nanofibrous scaffolds are highly porous (87-94%) with ultimate tensile strength observed in the range of 1.51-4.86MPa and also showed better hydrophilic properties after addition of AA, TC and n-HA. Human mesenchymal stem cells (MSCs) cultured on these bio-composite nanofibrous scaffolds and stimulated to osteogenic differentiation in the presence of AA/TC/n-HA for BTE. The cell proliferation and biomaterial interactions were studied using MTS assay, SEM and CMFDA dye exclusion methods. Osteogenic differentiation of MSCs was proven by using alkaline phosphatase activity, mineralization and double immunofluorescence staining of both CD90 and osteocalcin. The observed results suggested that the fabricated PLACL/SF/AA/TC/n-HA biocomposite hybrid nanofibrous scaffolds have good potential for the differentiation of MSCs into osteogenesis for bone tissue engineering.

Heart failure due to Myocardial Infarction (MI) remains the leading cause of death worldwide due to the inability of myocardial tissue to regenerate following infarction. Current therapies could only retard the progression of disease, but fails to bring functional improvement and cardiac regeneration. The present study analyzes the potentials of Poly(glycerol sebacate)/Fibrinogen (PGS/Fib) core/shell fibers as a structural support and initial entrapment of cells in an in vivo porcine model using echocardiography, histology, and immunohistochemistry. The echocardiography results showed the increased ejection fraction (EF) in PGS/Fib/VEGF/Cells compared with MI controls. The percentage increase in the End Diastolic Volume (EDV) dimension from post MI period to 4 weeks follow-up was the least in PGS/Fib/VEGF/Cells groups compared with MI and cell control group proving that the PGS/Fib/VEGF/Cells group restored the left ventricle (LV) function after MI, evident from the improvement in EF and prevention of LV enlargement. Further, immunohistochemistry results demonstrated that most of the transplanted mesenchymal stem cells (MSCs) within the PGS/Fib/VEGF scaffolds expressed cardiac marker proteins troponin and actinin and endothelial cell marker protein CD31 indicating differentiation of human bone marrow MSCs into cardiac cells and endothelial cells. The developed nanofibrous cardiac patch PGS/Fib/VEGF/Cells provides both functional and structural integrity to the infarcted myocardium and also serves as a suitable matrix for the entrapment of MSCs in clinical applications for cardiac tissue engineering.

Controlled delivery of drugs is one of the widely explored areas in biomedicine and healthcare. Biocompatible nanofibers are explored as potential drug delivery vehicles in recent years in the field of tissue engineering. The present study fabricated polycaprolactone (PCL) nanofibers with different concentrations of antibiotic drug tetracycline hydrochloride (TC) for the controlled drug delivery. Chloroform and methanol (3:1) used as the solvent system for the fabrication of PCL/TC nanofibers. The observed results showed that the PCL exhibited a transition from hydrophobic to hydrophilic state with time due to TC loading for the controlled release. Tetracycline hydrochloride (5%) drug loaded membranes showed the highest resistance to deformation, while 2% drug membrane had the highest tensile strength at 3.9 MPa. Porosity of the fibrous scaffolds increased with increase in concentration of the drugs. In vitro release studies of the drug analyzed by UV-Visible Spectrometry indicated the burst release of drug within the first hour observed minimum and was followed by sustained control release for a period of eight days. PCL loaded with TC shows the potential as promising substrate for drug delivery applications in biomedicine and healthcare.

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), are characterized by progressive loss (and even death) of structure and function of neurons, and have created great burden to the individual and the society. The actual cause of various neurodegenerative diseases still remains a mystery in healthcare. Some of the commonly studied environmental factors causes for neurodegenerative diseases are protein degradation, oxidative stress, inflammation, environmental factor, mitochondrial defects, familial history, and abnormal protein accumulation in neuron. However ageing plays a very important role in neurodegenerative diseases. Medicinal plants and natural compounds, such as Withania somnifera (ashwagandha), Ginseng, curcumin, resveratrol, Baccopa monnieri, Ginkgo biloba, and Wolfberry have been applied to prevent or alleviate neurological diseases and relief of neurological symptoms reported in in vivo or in clinical trails. Natural compounds in nanosize range as a therapeutic agent possess the same activity as in native state. Nanodrug delivery helps to increase the bioavailability of the drug and thereby specifically target cells and tissues. Nanoparticles, polymeric nanomicelles, complex polymers nanocrystal, and nanofibers are used to carry the medicinal plants for drug delivery system in the treatment of neurodegenerative diseases. Especially, electrospinning and electrospraying as straightforward yet versatile techniques for the production of nanosized fibers and particles possess huge potential in encapsulation of natural compounds for the neurodegenerative diseases. This review is a study to understand the role of nanotechnology and natural compounds in neurodegenerative diseases associated with ageing.

Glass-ionomer cements (GICs) have been widely used for over forty years, because of their desirable properties in dentistry. The most important advantages of the GICs are associated with their ability to release long-term antimicrobial agents. However, GICs used as restorative materials have still lots of challenges due to their secondary caries and low mechanical properties. Recent studies showed that the fluoride-releasing activity of conventional GICs is inadequate for effectual antibacterial conservation in many cases. Therefore, many efforts have been proposed to modify the antibacterial features of GICs in order to prevent the secondary caries. Particularly, for achieving this goal GICs were incorporated into various biomaterials possessing antibacterial activities. The scope of this review is to assess systematically the extant researches addressing the antibacterial modifications in GICs in order to provide with an authoritative, at the same time in-depth understanding of controlled antibacterial release in this class of biomaterials. It also gives a whole perspective on the future developments of GICs and challenges related to antibacterial GICs.

A biomimetic Zein polydopamine based nanofiber scaffold was fabricated to deliver bone morphogenic protein-2 (BMP-2) peptide conjugated titanium dioxide nanoparticles in a sustained manner for investigating its osteogenic differentiation potential. To prolong its retention time at the target site, BMP-2 peptide has been conjugated to titanium dioxide nanoparticles owing to its high surface to volume ratio. The effect of biochemical cues from BMP-2 peptide and nanotopographical stimulation of electrospun Zein polydopamine nanofiber were examined for its enhanced osteogenic expression of human fetal osteoblast cells. The sustained delivery of bioactive signals, improved cell adhesion, mineralization, and differentiation could be attributed to its highly interconnected nanofibrous matrix with unique material composition. Further, the expression of osteogenic markers revealed that the fabricated nanofibrous scaffold possess better cell-biomaterial interactions. These promising results demonstrate the potential of the composite nanofibrous scaffold as an effective biomaterial substrate for bone regeneration.

Recent advances in bioprinting technology have been used to precisely dispense cell-laden biomaterials for the construction of complex 3D functional living tissues or artificial organs. Organ printing and biofabrication provides great potential for the freeform fabrication of 3D living organs using cellular spheroids, biocomposite nanofibers, or bioinks as building blocks for regenerative therapy. Vascularization is often identified as a main technological barrier for building 3D organs in tissue engineering. 3D printing of living tissues starts with potential support of biomaterials to maintain structural integrity and degradation of certain time periods after printing of the scaffolds. Biofabrication is the production of complex living and nonliving biological products from raw materials such as cells, molecules, ECM, and biomaterials. Generally, two basic methods are used for the fabrication of scaffolds such as conventional/traditional fabrication processes and advance fabrication processes for engineering organs. A wide range of polymers and biomaterials are used for the fabrication of scaffolds in tissue engineering applications. 3D additive manufacturing is advancing day-by-day; however, there are various critical challenging factors used for fabricating 3D scaffolds. This review is aimed at understanding the various scaffold fabrication techniques, types of polymers and biomaterials used for the fabrication processes, various fields of applications, and different challenges faced in their fabrication of scaffolds in regenerative therapy.

Nanotechnology being one of the most promising technologies today shows an extremely huge potential in the field of tissue engineering to mimic the porous topography of natural extracellular matrix (ECM). Natural polymers are incorporated into the synthetic polymers to fabricate functionalized hybrid nanofibrous scaffolds, which improve cell and tissue compatibility. The present study identified the biopolymers – aloe vera, silk fibroin and curcumin incorporated into polycaprolactone (PCL) as suitable substrates for tissue engineering. Different combinations of PCL with natural polymers – PCL/aloe vera, PCL/silk fibroin, PCL/aloe vera/silk fibroin, PCL/aloe vera/silk fibroin/curcumin were electrospun into nanofibrous scaffolds. The fabricated two dimensional nanofibrous scaffolds showed high surface area, appropriate mechanical properties, hydrophilicity and porosity, required for the regeneration of diseased tissues. The nanofibrous scaffolds were characterized by Scanning electron microscope (SEM), porometry, Instron tensile tester, VCA optima contact angle measurement and FTIR to analyze the fiber diameter and morphology, porosity and pore size distribution, mechanical strength, wettability, chemical bonds and functional groups, respectively. The average fiber diameter of obtained fibers ranged from 250 nm to 350 nm and the tensile strength of PCL scaffolds at 4.49 MPa increased upto 8.3 MPa for PCL/silk fibroin scaffolds. Hydrophobicity of PCL decreased with the incorporation of natural polymers, especially for PCL/aloe vera scaffolds. The properties of as-spun nanofiber scaffolds showed their potential as promising scaffold materials in tissue engineering applications.

Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(l-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering.

Reproducible buckled and porous sub-micron diameter polycaprolactone (PCL) fibers were produced by simple electrospinning process for biomedical applications. In this study, six types of solvent combinations with different vapor pressures were used to study the effect of phase separation on the morphology of electrospun fibers. The fiber morphology, Infrared spectroscopy, water contact angle and tensile test were performed to study the material properties. It is evident that the fiber morphology was affected by solvent combinations used for the fabrication of sub-micron fibers. The solution viscosity, the collecting distance and the type of solvent combination used could be an optimum parameter for the generation of porous-buckled fibers with narrow pore size distribution. The simplicity of the set-up is the immense advantage for producing buckled and porous elastomeric fibers for tissue engineering applications. All the fibers were spun on a motionless collector plate to study the properties of fibers. The combination of surface pores with the buckled pattern could be of great importance in the field of biomedical engineering.

Liver tissue engineering using polymeric nanofibrous scaffold and stem cells holds great promises for treating end-stage liver failures. The aim of this study was to evaluate hepatic trans-differentiation potential of human mesenchymal stem cells (hMSCs) on a biomagnetic electrospun nanofibrous scaffold fabricated from a blend of poly-l-lactide (PLLA), collagen and fibrin-rich blood clot, under the influence of a low frequency magnetic field. The scaffold was characterized for surface properties, biochemical and biomechanical parameters and bio-magnetic behaviour. Cell proliferation assay revealed that the scaffold was suitable for hMSCs adhesion and proliferation. Hepatic trans-differentiation potential of hMSCs was augmented on nanofibrous scaffold in magnetic field exposure group compared to control groups, as evident by strong expression of hepatocyte specific markers, albumin release, urea synthesis and presence of an inducible cytochrome P450 system. Our results conclude that biomagnetic scaffold of PLLA/collagen/blood clot augments hepatic trans-differentiation of hMSCs under magnetic field influence. � 2014, Springer Science+Business Media New York.

Plant-derived natural products are being used in medicine, and they are easily available for the production and use in tissue engineering based biological applications. Utilization of plant materials to treat human diseases is a common practice followed over many decades. In fact plant and its derivatives have been actively included in health management over thousands of years. The advent of phytochemical and phytopharmacological sciences has opened an arena to elucidate the structural and biological composition of several medicinal plant products. Their pharmacological effects depend on the supply of highly active water soluble compounds; however, due to their large molecular size most compounds are unable to cross the lipid membranes of the cells and therefore result in poor absorption resulting in loss of bioavailability and efficacy. Electrospinning makes it possible to combine the advantages of utilizing these plant materials in the form of nanofibrous scaffolds for delivering the active constituent at a sufficient concentration during the entire treatment period to the host site. The aim of this review is to highlight the potential applications of electrospun nanofibrous scaffolds based systems and herbal medicines in tissue engineering.

Wound healing is a major problem in diabetic patients and current methods of treatment have met with limited success. Since skin cell renewal is under the control of mesenchymal stem cells (MSCs) treatment of wounds has been attempted with the application of exogenous bone marrow MSCs (hBMMSCs). However, hBMMSCs have the limitations of painful harvest, low cell numbers and short-lived stemness properties unlike MSCs from the Wharton's jelly of human umbilical cords (hWJSCs). Since nanoscaffolds provide three dimensional architectural patterns that mimic in vivo stem cell niches and aloe vera has antibacterial properties we evaluated the use of an aloe vera-polycaprolactone (AV/PCL) nanoscaffold impregnated with green fluorescent protein (GFP)-labeled hWJSCs (GFP-hWJSCs + AV/PCL) or its conditioned medium (hWJSC-CM + AV/PCL) for healing of excisional and diabetic wounds. In skin fibroblast scratch-wound assays exposed to GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL, fibroblasts migrated significantly faster from edges of scratches into vacant areas together with increased secretion of collagen I and III, elastin, fibronectin, superoxide dismutase, and metalloproteinase-1 (MMP-1) compared to controls. After one application of GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL excisional and diabetic wounds in mice showed rapid wound closure, reepithelialization, and increased numbers of sebaceous glands and hair follicles compared to controls. The same wounds exposed to GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL also showed positive keratinocyte markers (cytokeratin, involucrin, filaggrin) and increased expression of ICAM-1, TIMP-1, and VEGF-A compared to controls. AV/PCL nanoscaffolds in combination with hWJSCs appear to have synergistic benefits for wound healing.

Aloe vera (AV) is one of the medicinal herbs with a well-established spectrum of wound healing, antimicrobial and anti-inflammatory property. AV-mediated therapeutics present significant tissue regenerative activity by modulating the inflammatory and proliferative phases of wound healing. The purpose of the present work was to combine the biological properties of AV and the advantages of electrospun meshes to prepare a potent transdermal biomaterial. The polycaprolactone (PCL) containing 5 and 10 wt % of lyophilized powder of AV was studied for electrospinning into nanoscale fiber mats and compared with PCL/Collagen blend for dermal substitutes. SEM revealed the average diameters of PCL, PCL-AV 5 %, PCL-AV 10 % and PCL/Collagen nanofiber scaffolds in the range of 519 ± 28, 264 ± 46, 215 ± 63 and 249 ± 52 nm, respectively. PCL-AV 10 % nanofiber scaffolds showed finer fiber morphology with improved hydrophilic properties and higher tensile strength of 6.28 MPa with a Young’s modulus of 16.11 MPa desirable for skin tissue engineering. The nanofibers were then used to investigate differences in biological responses in terms of proliferation and cell morphology of mice dermal fibroblasts. It was found that PCL-AV 10 % nanofibrous matrix favored cell proliferation compared to other scaffolds which almost increased linearly by (p ≤ 0.01) 17.79 % and (p ≤ 0.01) 21.28 % compared to PCL on sixth and ninth day. CMFDA dye expression, secretion of collagen and F-actin expression were significantly increased in PCL-AV 10 % scaffolds compared to other nanofibrous scaffolds. The obtained results proved that the PCL-AV 10 % nanofibrous scaffold is a potential biomaterial for skin tissue regeneration.

Aloe vera (AV) and tetracycline hydrochloride (TCH) exhibit significant properties such as anti-inflammatory, antioxidant and anti-bacterial activities to facilitate skin tissue engineering. The present study aims to develop poly-&epsilon, caprolactone (PCL)/ AV containing curcumin (CUR), and TCH loaded hybrid nanofibrous scaffolds to validate the synergistic effect on the fibroblast proliferation and antimicrobial activity against Gram-positive and Gram-negative bacteria for wound healing. PCL/AV, PCL/CUR, PCL/AV/CUR and PCL/AV/TCH hybrid nanofibrous mats were fabricated using an electrospinning technique and were characterized for surface morphology, the successful incorporation of active compounds, hydrophilicity and the mechanical property of nanofibers. SEM revealed that there was a decrease in the fiber diameter (ranging from 360 to 770 nm) upon the addition of AV, CUR and TCH in PCL nanofibers, which were randomly oriented with bead free morphology. FTIR spectra of various electrospun samples confirmed the successful incorporation of AV, CUR and TCH into the PCL nanofibers. The fabricated nanofibrous scaffolds possessed mechanical properties within the range of human skin. The biocompatibility of electrospun nanofibrous scaffolds were evaluated on primary human dermal fibroblasts (hDF) by MTS assay, CMFDA, Sirius red and F-actin stainings. The results showed that the fabricated PCL/AV/CUR and PCL/AV/TCH nanofibrous scaffolds were non-toxic and had the potential for wound healing applications. The disc diffusion assay confirmed that the electrospun nanofibrous scaffolds possessed antibacterial activity and provided an effective wound dressing for skin tissue engineering.

Polycaprolactone (PCL), a synthetic biocompatible and biodegradable polymer generally used as a scaffold material for tissue engineering applications. The high stiffness and hydrophobicity of the PCL fiber mesh does not provide significant cell attachment and proliferation in cardiac tissue engineering. Towards this goal, the study focused on a compound of PCL and oligomer hydrogel [Bisphenol A ethoxylated dimethacrylate (BPAEDMA)] processed into electrospun nanofibrous scaffolds. The composition, morphology and mechanical properties of the compound scaffolds, composed of varying ratios of PCL and hydrogel were characterized by scanning electron microscopy, infrared spectroscopy and dynamic mechanical analyzer. The elastic modulus of PCL/BPAEDMA nanofibrous scaffolds was shown to be varying the BPAEDMA weight fraction and was decreased by increasing the BPAEDMA weight fraction. Compound fiber meshes containing 75 wt % BPAEDMA oligomer hydrogel exhibited lower modulus (3.55 MPa) and contact angle of 25(o) . Rabbit cardiac cells cultured for 10 days on these PCL/BPAEDMA compound nanofibrous scaffolds remained viable and expressed cardiac troponin and alpha-actinin proteins for the normal functioning of myocardium. Cell adhesion and proliferations were significantly increased on compound fiber meshes containing 75 wt % BPAEDMA, when compared with other nanofibrous scaffolds. The results observed that the produced PCL/BPAEDMA compound nanofibrous scaffolds promote cell adhesion, proliferation and normal functioning of cardiac cells to clinically beneficial levels, relevant for cardiac tissue engineering.