Damia Mawad

Photochemical tissue bonding with chitosan adhesive films

BackgroundPhotochemical tissue bonding (PTB) is a promising sutureless technique for tissue repair. PTB is often achieved by applying a solution of rose bengal (RB) between two tissue edges, which are irradiated by a green laser to crosslink collagen fibers with minimal heat production. In this study, RB has been incorporated in chitosan films to create a novel tissue adhesive that is laser-activated.MethodsAdhesive films, based on chitosan and containing ~0.1 wt% RB were manufactured and bonded to calf intestine by a solid state laser (λ = 532 nm, Fluence~110 J/cm2, spot size~0.5 cm). A single-column tensiometer, interfaced with a personal computer, tested the bonding strength. K-type thermocouples recorded the temperature (T) at the adhesive-tissue interface during laser irradiation. Human fibroblasts were also seeded on the adhesive and cultured for 48 hours to assess cell growth.ResultsThe RB-chitosan adhesive bonded firmly to the intestine with adhesion strength of 15 ± 2 kPa, (n = 31). The adhesion strength dropped to 0.5 ± 0.1 (n = 8) kPa when the laser was not applied to the adhesive. The average temperature of the adhesive increased from 26°C to 32°C during laser exposure. Fibroblasts grew confluent on the adhesive without morphological changes.ConclusionA new biocompatible chitosan adhesive has been developed that bonds photochemically to tissue with minimal temperature increase.

Emulsion-coaxial electrospinning: designing novel architectures for sustained release of highly soluble low molecular weight drugs

In drug therapy, most therapeutic drugs are of low molecular weight and could freely diffuse in the biological milieu depending on the administration route applied. The main reason for the development of polymeric drug carriers is to obtain desired effects such as sustained therapy, local and controlled release, prolonged activity and reduction of side effects. Alternatively, polymeric carriers can be made bioerodible in order to be eliminated by natural ways after a certain time of therapy. Core–shell fibres from coaxial spinneret or emulsion electrospinning are good candidates for the development of such devices; however difficulties remain especially in controlling the release over a sustained period. Here, we present a novel technique combining coaxial and emulsion electrospinning to produce micro-structured core–shell fibres. The design of drug microreservoirs of variable size within the bulk of the fibre combined with a tailored diffusive barrier allows modulating the release kinetics of these novel carriers. A nearly constant and linear release of the model drug Levetiracetam (Mw ≈ 170 g mol−1) from PLGA emulsion-coaxial electrospun fibres is observed over 20 days. This device is aimed to be implanted into the brain for the treatment of epilepsy and is an example of the new capabilities and the promising potential that emulsion-coaxial electrospinning can provide towards the development of future drug carriers.

Network structure and macromolecular drug release from poly(vinyl alcohol) hydrogels fabricated via two crosslinking strategies

Injectable hydrogels have potential biomedical applications ranging from tissue fillers to drug delivery vehicles. This study focussed on evaluating the structure of poly(vinyl alcohol) (PVA) hydrogels of variable solid content and high molecular weight model drug release from the networks formed via either conventional photo-polymerization compared with chemical initiation of polymerization using an oxidation-reduction (redox) reaction. Swelling behaviour was characterised in water to assess the structural properties. Model drugs, FITC-Dextran, 20 kDa (FD20) and 4 kDa (FD4) were loaded in the hydrogels prior to curing and drug release studies conducted. Redox-cured hydrogels were more swollen than UV-cured systems, lost approximately 20% of their polymer mass compared to only 5% from UV-cured hydrogels and subsequently exhibited networks of larger mesh sizes. Also, networks of variable solid contents showed different structural properties with systems of higher polymer concentration exhibiting a smaller mesh size. The difference in structural properties of the networks affected release of FD20, being faster in redox-cured than UV-cured hydrogels, and slower from systems of higher solid content. Release of FD4 was faster than FD20 from networks of same solid content. This study suggested that PVA hydrogels can be cured by redox-initiation to function as a controlled delivery system for macromolecular drugs.

Elaboration of radiopaque iodinated nanoparticles for in situ control of local drug delivery

Drug delivery systems can benefit from intrinsic radiopacity as this property will allow following up the diffusion path of the nanoparticles containing the therapeutic drug after their local administration. Herein, we report the synthesis of iodinated derivatives of cellulose acetate (CA) and their formulation into aqueous radiopaque nanoparticle suspensions. Modification and purification of CA with mono- or tri-iodobenzoyl chloride were characterized by NMR spectroscopy and elemental analysis of iodine. In particular, measurements of diffusion coefficients by the DOSY 2D NMR method allowed controlling the complete elimination of non-grafted iodinated materials. Pure radiopaque CA was successfully achieved with an iodine content varying between 14 and 32%. Aqueous suspensions of nanoparticles were successfully formed, characterized by being spherical, <100 nm in size and stable as a suspension over 3 months. The degree of substitution, in particular the triiodo moieties, imparted a good level of radiopacity whether in dry powder form (2627 HU) or as a nanoparticle suspension (298 HU). These values are comparable to radiopacity of systems reported in literature to be in vivo visible. Loading of paclitaxel was successfully attempted, suggesting that the developed radiopaque nanoparticles can ultimately function as a drug delivery system.

Elucidating the deprotonation of polyaniline films by X-ray photoelectron spectroscopy

Spin-coated polyaniline (PANI) thin films can be made conductive following treatment with a dopant (reducing or oxidising agent). However, de-doping results in loss of electrical properties. We chemically doped PANI films using p-toluene sulfonic acid (pTSA) and camphor sulfonic acid (CSA) and examined their ability to retain these dopants and their conductive properties in physiological media. Changes in the protonation level of these films were assessed by N 1s core line spectra in X-ray photoelectron spectroscopy (XPS). PANI films were found to de-dope with a decrease in the ratio of N 1s photoelectron signal corresponding to positively charged nitrogen (i.e. –NH2+, NH+) to the total N 1s signal. De-doping of PANI films was confirmed by depletion of the dopant fragment (–SO3−) as determined from both XPS and atomic distribution in Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) images. XPS has been successfully used as a tool to elucidate the deprotonation of PANI films and the loss of the dopant from the bulk.

Advances in hydrogels applied to degenerative diseases.

Hydrogels are currently applied in the treatment of numerous degenerative diseases because of their three dimensional (3D) nature, high water content and wide range of polymers that can be used for their fabrication. Hydrogels have been investigated and commercialized, for example, as soft contact lens-based ophthalmic drug delivery systems. These novel devices improved the bioavailability of ophthalmic drugs and their residence time. Hydrogels are also being investigated to facilitate and augment targeted delivery of chemotherapeutic agents. This approach minimizes significantly the side effects associated with conventional administration of anti-cancer therapeutics. The application of hydrogels as 3D scaffold has recently gained momentum because they can mimic key features of the extracellular matrix. For this reason, hydrogels are representing a viable alternative to traditional tumor xenograft in cancer biology studies. This review highlights recent advances in the development of hydrogels that are applied in degenerative diseases such as ocular, cancer, spine and cartilage degenerative pathologies.

An in vitro study of the photodynamic effect of rose bengal on Trichophyton rubrum.

Onychomycosis, a fungal infection of the finger or toenails, is predominantly caused by Trichophyton rubrum. Treatment is difficult due to high recurrence rates and problems with treatment compliance. For these reasons, alternative therapies are needed. Here we describe the photoactivation of Rose Bengal (RB) using a green laser (λ = 532 nm) at fluences of 68, 133 and 228 J/cm(2) , and assess its fungicidal activity on T. rubrum spore suspensions. A 140 µM RB solution was able to induce a fungicidal effect on T. rubrum when photosensitized with the fluence of 228 J/cm(2) . RB photosensitization using a green laser provides a potential novel treatment for T. rubrum infections.

A conducting polymer with enhanced electronic stability applied in cardiac models

Researchers develop sutureless conductive patch with enhanced biostability and effect on heart conduction velocity. Electrically active constructs can have a beneficial effect on electroresponsive tissues, such as the brain, heart, and nervous system. Conducting polymers (CPs) are being considered as components of these constructs because of their intrinsic electroactive and flexible nature. However, their clinical application has been largely hampered by their short operational time due to a decrease in their electronic properties. We show that, by immobilizing the dopant in the conductive scaffold, we can prevent its electric deterioration. We grew polyaniline (PANI) doped with phytic acid on the surface of a chitosan film. The strong chelation between phytic acid and chitosan led to a conductive patch with retained electroactivity, low surface resistivity (35.85 ± 9.40 kilohms per square), and oxidized form after 2 weeks of incubation in physiological medium. Ex vivo experiments revealed that the conductive nature of the patch has an immediate effect on the electrophysiology of the heart. Preliminary in vivo experiments showed that the conductive patch does not induce proarrhythmogenic activities in the heart. Our findings set the foundation for the design of electronically stable CP-based scaffolds. This provides a robust conductive system that could be used at the interface with electroresponsive tissue to better understand the interaction and effect of these materials on the electrophysiology of these tissues.

Conductive Polymer Hydrogels

Combining electrical properties with synthetic scaffolds such as hydrogels is an attractive approach for the design of the ideal synthetic soft tissue, one that mimics the architecture of the native extracellular matrix and provides the electronic functionality needed for cell–cell communication. Conducting polymers (CPs) are carbon-based polymers that are electronically active and consequently are being investigated as the structural material for fabrication of electroactive hydrogels. CPs are attractive in that they could be processed in various forms, their chemistry could be modified to introduce different functionalities and most important is their capability to conduct electrons. In this chapter, electroconductive hydrogels (ECHs) fabricated from CP either as a single component or as an additive to conventional hydrogel networks are reviewed.

Electroconductive Hydrogel Based on Functional Poly(Ethylenedioxy Thiophene)

Poly(ethylene dioxythiophene) with functional pendant groups bearing double bonds is synthesized and employed for the fabrication of electroactive hydrogels with advantageous characteristics: covalently cross-linked porous 3D scaffolds with notable swelling ratio, appropriate mechanical properties, electroactivity in physiological conditions, and suitability for proliferation and differentiation of C2C12 cells. This is a new approach for the fabrication of conductive engineered constructs.