Brisa Peña

Characterization of polysulfone and polysulfone/vanillin microcapsules by 1H NMR spectroscopy, solid-state 13C CP/MAS-NMR spectroscopy, and N2 adsorption-desorption analyses.

Textile detergent and softener industries have incorporated perfume microencapsulation technology to improve their products. Perfume encapsulation allows perfume protection until use and provides a long-lasting fragrance release. But, certain industrial microcapsules show low encapsulation capacity and low material stability. Polysulfone capsules have been already proposed to solve these drawbacks. Among them, PSf/Vanillin capsules were considered as a desirable system. They present both good material stability and high encapsulation capacity. However, several factors such as the final location of the perfume in the polymeric matrix, the aggregation state that it has in the capsule and its interaction with the capsule components have not been studied yet. These factors can provide vast information about the capsule performance and its improvement. With the aim to characterize these parameters, the physical and chemical properties of PSf/Vanillin capsules have been investigated by nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and N(2) adsorption-desorption measurements. AFM micrograph and N(2) isotherms confirm that the presence of vanillin modify the physical structure of PSf/Vanillin microcapsules as it is trapped in the capsule porosity. NMR results show that vanillin is present in solid state in PSf/Vanillin microcapsules.

Biomimetic Polymers for Cardiac Tissue Engineering.

Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.

A heparin-mimicking reverse thermal gel for controlled delivery of positively charged proteins

Positively charged therapeutic proteins have been used extensively for biomedical applications. However, the safety and efficacy of proteins are mostly limited by their physical and chemical instability and short half-lives in physiological conditions. To this end, we created a heparin-mimicking sulfonated reverse thermal gel as a novel protein delivery system by sulfonation of a graft copolymer, poly(serinol hexamethylene urea)-co-poly(N-isopropylacylamide), or PSHU-NIPAAm. The net charge of the sulfonated PSHU-NIPAAm was negative due to the presence of sulfonate groups. The sulfonated PSHU-NIPAAm showed a typical temperature-dependent sol-gel phase transition, where polymer solutions turned to a physical gel at around 32°C and maintained gel status at body temperature. Both in vitro cytotoxicity tests using C2C12 myoblast cells and in vivo cytotoxicity tests by subcutaneous injections demonstrated excellent biocompatibility. In vitro release tests using bovine serum albumin revealed that the release from the sulfonated PSHU-NIPAAm was more sustained than that from the plain PSHU-NIPAAm. Furthermore, this sulfonated PSHU-NIPAAm system did not affect protein structure after 70-day observation periods.

A Self-Assembling Injectable Biomimetic Microenvironment Encourages Retinal Ganglion Cell Axon Extension in Vitro

Sensory-somatic nervous system neurons, such as retinal ganglion cells (RGCs), are typically thought to be incapable of regenerating. However, it is now known that these cells may be stimulated to regenerate by providing them with a growth permissive environment. We have engineered an injectable microenvironment designed to provide growth-stimulating cues for RGC culture. Upon gelation, this injectable material not only self-assembles into laminar sheets, similar to retinal organization, but also possesses a storage modulus comparable to that of retinal tissue. Primary rat RGCs were grown, stained, and imaged in this three-dimensional scaffold. We were able to show that RGCs grown in this retina-like structure exhibited characteristic long, prominent axons. In addition, RGCs showed a consistent increase in average axon length and neurite-bearing ratio over the 7 day culture period, indicating this scaffold is capable of supporting substantial RGC axon extension.

Injectable Carbon Nanotube-Functionalized Reverse Thermal Gel Promotes Cardiomyocytes Survival and Maturation

The ability of the adult heart to regenerate cardiomyocytes (CMs) lost after injury is limited, generating interest in developing efficient cell-based transplantation therapies. Rigid carbon nanotubes (CNTs) scaffolds have been used to improve CMs viability, proliferation, and maturation, but they require undesirable invasive surgeries for implantation. To overcome this limitation, we developed an injectable reverse thermal gel (RTG) functionalized with CNTs (RTG-CNT) that transitions from a solution at room temperature to a three-dimensional (3D) gel-based matrix shortly after reaching body temperature. Here we show experimental evidence that this 3D RTG-CNT system supports long-term CMs survival, promotes CMs alignment and proliferation, and improves CMs function when compared with traditional two-dimensional gelatin controls and 3D plain RTG system without CNTs. Therefore, our injectable RTG-CNT system could potentially be used as a minimally invasive tool for cardiac tissue engineering efforts.

Novel insights into cardiomyocytes provided by atomic force microscopy

Cardiovascular diseases (CVDs) are the number one cause of death globally, therefore interest in studying aetiology, hallmarks, progress and therapies for these disorders is constantly growing. Over the last decades, the introduction and development of atomic force microscopy (AFM) technique allowed the study of biological samples at the micro- and nanoscopic level, hence revealing noteworthy details and paving the way for investigations on physiological and pathological conditions at cellular scale. The present work is aimed to collect and review the literature on cardiomyocytes (CMs) studied by AFM, in order to emphasise the numerous potentialities of this approach and provide a platform for researchers in the field of cardiovascular diseases. Original data are also presented to highlight the application of AFM to characterise the viscoelastic properties of CMs.

Injectable Hydrogels for Cardiac Tissue Engineering

In light of the limited efficacy of current treatments for cardiac regeneration, tissue engineering approaches have been explored for their potential to provide mechanical support to injured cardiac tissues, deliver cardio-protective molecules, and improve cell-based therapeutic techniques. Injectable hydrogels are a particularly appealing system as they hold promise as a minimally invasive therapeutic approach. Moreover, injectable acellular alginate-based hydrogels have been tested clinically in patients with myocardial infarction (MI) and show preservation of the left ventricular (LV) indices and left ventricular ejection fraction (LVEF). This review provides an overview of recent developments that have occurred in the design and engineering of various injectable hydrogel systems for cardiac tissue engineering efforts, including a comparison of natural versus synthetic systems with emphasis on the ideal characteristics for biomimetic cardiac materials.