Radhakrishnan Sridhar

Electrospun composite nanofibers and their multifaceted applications

The re-exploration of the nanostructure production technique known as electrospinning was carried out in the past decade due to its simplicity and uniqueness of producing nanostructures. As nanotechnology is one of the most promising and growing technologies today, a large amount of work is being carried out in an extensive area and shows an extremely huge potential for miraculous works in the fields of medicine and biotechnology. These nanostructures were found to be of great significance because of their inherent properties such as large surface area to volume ratio and the engineered properties such as porosity, stability and permeability. The functionality and applicability of these nanostructures were further improved by incorporating secondary phases either during electrospinning or in the post-processing resulting in the composite nanostructures. These secondary phases may include metal oxides, carbon nanotubes, precious metals, gold nanoparticles and hydroxyapatite. Nanofibrous materials that mimic the native extracellular matrix (ECM) and promote the adhesion of various cells are being developed as tissue-engineered scaffolds for the skin, bone, vasculature, heart, cornea, nervous system and other tissues. The article discusses in detail the applicability of these composite fibers in energy, sensors, filters, biotechnology and details the technological issues, research challenges and future trends.

Minimally invasive injectable short nanofibers of poly(glycerol sebacate) for cardiac tissue engineering

Myocardial tissue lacks the ability to appreciably regenerate itself following myocardial infarction (MI) which ultimately results in heart failure. Current therapies can only retard the progression of disease and hence tissue engineering strategies are required to facilitate the engineering of a suitable biomaterial to repair MI. The aim of this study was to investigate the in vitro properties of an injectable biomaterial for the regeneration of infarcted myocardium. Fabrication of core/shell fibers was by co-axial electrospinning, with poly(glycerol sebacate) (PGS) as core material and poly-L-lactic acid (PLLA) as shell material. The PLLA was removed by treatment of the PGS/PLLA core/shell fibers with DCM:hexane (2:1) to obtain PGS short fibers. These PGS short fibers offer the advantage of providing a minimally invasive injectable technique for the regeneration of infarcted myocardium. The scaffolds were characterized by SEM, FTIR and contact angle and cell-scaffold interactions using cardiomyocytes. The results showed that the cardiac marker proteins actinin, troponin, myosin heavy chain and connexin 43 were expressed more on short PGS fibers compared to PLLA nanofibers. We hypothesized that the injection of cells along with short PGS fibers would increase cell transplant retention and survival within the infarct, compared to the standard cell injection system.

Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole) electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical conformation of gelatin and the presence of gelatin decreased the hemolytic activity of polyenes. The polyene-loaded fiber mats were noncytotoxic to primary human corneal and sclera fibroblasts. The reduction of toxicity with complete retention of activity of the polyene antifungal-loaded gelatin fiber mats can provide new opportunities in the management of superficial skin infections.

Expression of cardiac proteins in neonatal cardiomyocytes on PGS/fibrinogen core/shell substrate for Cardiac tissue engineering

BACKGROUND Heart failure due to myocardial infarction remains the leading cause of death worldwide owing to the inability of myocardial tissue regeneration. The aim of this study is to develop a core/shell fibrous cardiac patch having desirable mechanical properties and biocompatibility to engineer the infarcted myocardium. METHOD We fabricated poly(glycerol sebacate)/fibrinogen (PGS/fibrinogen) core/shell fibers with core as elastomeric PGS provides suitable mechanical properties comparable to that of native tissue and shell as fibrinogen to promote cell-biomaterial interactions. The PGS/fibrinogen core/shell fibers and fibrinogen nanofibers were characterized by SEM, contact angle and tensile testing to analyze the fiber morphology, wettability, and mechanical properties of the scaffold. The cell-scaffold interactions were analyzed using isolated neonatal cardiomyocytes for cell proliferation, confocal analysis for the expression of marker proteins α-actinin, Troponin-T, β-myosin heavy chain and connexin 43 and SEM analysis for cell morphology. RESULTS We observed PGS/fibrinogen core/shell fibers had a Youngs modulus of about 3.28 ± 1.7 MPa, which was comparable to that of native myocardium. Neonatal cardiomyocytes cultured on these scaffolds showed normal expression of cardiac specific marker proteins α-actinin, Troponin, β-myosin heavy chain and connexin 43 to prove PGS/fibrinogen core/shell fibers have potential for cardiac tissue engineering. CONCLUSION Results indicated that neonatal cardiomyocytes formed predominant gap junctions and expressed cardiac specific marker proteins on PGS/fibrinogen core/shell fibers compared to fibrinogen nanofibers, indicating PGS/fibrinogen core/shell fibers may serve as a suitable cardiac patch for the regeneration of infarcted myocardium.

Review: the characterization of electrospun nanofibrous liquid filtration membranes

Electrospun nanofibrous membranes (ENMs) are used in a variety of applications, including sensors, tissue engineering, air filtration, energy, and reinforcement in composite materials. Recently, they have gained an interest in the field of liquid filtration. The membranes, surface, bulk, and overall architecture play an important role in the filtration properties and hence the right characterization technique needs to be established, which will pave the way for future developments in the field of filtration. In this article, we have reviewed the recent advances in ENMs for liquid separation application.

Electrosprayed nanoparticles for drug delivery and pharmaceutical applications

Nanotechnology based Pharma has emerged significantly and has influenced the Pharma industry up to a considerable extent. Nanoparticles technology holds a good share of the nanotech Pharma and is significant in comparison with the other domains. Electrospraying technology answers the potential needs of nanoparticle production such as scalability, reproducibility, effective encapsulation etc. Many drugs have been electrosprayed with and without polymer carriers. Drug release characteristics are improved with the incorporation of biodegradable polymer carriers which sustain the release of encapsulated drug. Electrospraying is acknowledged as an important technique for the preparation of nanoparticles with respect to pharmaceutical applications. Herein we attempted to consolidate the reports pertaining to electrospraying and their corresponding therapeutic application area.

Vitamin B12 loaded polycaprolactone nanofibers: a novel transdermal route for the water soluble energy supplement delivery.

Biocompatible PCL polymer nanofiber mediated sustained release of hydrophilic drug and applicability as transdermal delivery system is attempted. This new attempt to investigate water soluble vitamin delivery with hydrophobic polymer nanofiber sustained the release of the vitamin and the method is suited for the transdermal patch applications. The drug loaded fibers were characterized with SEM for morphology, porometer for pore size measurements, mechanical strength calculation and FT-IR for drug load characterization. The contact angle measurement showed surface wettability and controlled release of drug was quantified with UV absorption measurements. To further enhance the release of vitamin, the polymer fiber was plasma treated at different time intervals and made hydrophilic gradually. Since the increased surface area and drug encapsulation in nano-reservoirs can able to release drug in small quantities and in a sustained manner we attempted the release of the energy supplement with nanofibrous delivery mode.

Mimicking Native Extracellular Matrix with Phytic Acid‐Crosslinked Protein Nanofibers for Cardiac Tissue Engineering

A functional scaffold fabricated is developed from natural polymers, favoring regeneration of the ischemic myocardium. Hemoglobin/gelatin/fibrinogen (Hb/gel/fib) nanofibers are fabricated by electrospinning and are characterized for morphology, scaffold composition, functional groups and hydrophilicity. It is hypothesized that ex vivo pretreatment of mesenchymal stem cells (MSCs) using 5-azacytidine and such a functional nanofibrous construct having a high oxygen-carrying potential could lead to enhanced cardiomyogenic differentiation of MSCs and result in superior biological and functional effects. The combination of a functional nanofibrous scaffold composed of natural polymers and crosslinked with a natural crosslinking agent, phytic acid, and stem cell biology may prove to be a novel therapeutic device for treatment of myocardial infarction.

Cardiogenic differentiation of mesenchymal stem cells with gold nanoparticle loaded functionalized nanofibers

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.

Electrospun inorganic and polymer composite nanofibers for biomedical applications.

Engineered nanofibers are generally focused on filtration, solar cells, sensors, smart textile fabrication, tissue engineering, etc. Electrospun nanofibers have potential advantages in tissue engineering and regenerative medicine, because of the ease in the incorporation of drugs, growth factors, natural materials, and inorganic nanoparticles in to these nanofiber scaffolds. Electrospun nanofiber scaffolds composed of synthetic and natural polymers are being explored as scaffolds similar to natural extracellular matrix for tissue engineering. The requirement of the inorganic composites in the nanofiber scaffolds for favouring hard and soft tissue engineering applications is dealt in detail in the present review. Regarding drug delivery applications of the composite nanofibers, the review emphasizes on wound healing with silver nanoparticles incorporated nanofibers, bone tissue engineering, and cancer chemotherapy with titanium and platinum complexes loaded nanofibers. The review also describes gold nanoparticle loaded nanofibers for cancer diagnosis and cosmetic applications.