Bioinspired Oligo-Urethane Nanoparticles for Delivering Exogenous C-Type Natriuretic Peptide: Synthetic Biomaterial Nanocarrier Complexes and Their Interactions with Cardiac Myofibroblasts.

In a healthy heart, cells naturally secrete C-type natriuretic peptide (CNP), a cytokine that protects against myofibroblast differentiation of cardiac fibroblasts and extracellular matrix deposition leading to fibrosis. CNP availability during myocardial remodeling is important to prevent cardiac fibrosis, but CNP is limited after an injury because of the loss of cardiomyocytes and the activation of cardiac fibroblasts to myofibroblasts. We hypothesized that the sustained release of exogenous CNP from oligo-urethane nanoparticles (NPs) would reduce differentiation of human cardiac fibroblasts toward a myofibrogenic phenotype. Our work used a modified form of a degradable polar hydrophobic ionic (D-PHI) oligo-urethane, which has shown the ability to self-assemble into NPs for the delivery of peptide and oligonucleotide biomolecules. The CNP-loaded NPs (NPCNP) were characterized for a diameter of 129 ± 1.4 nm and a ζ potential of -46 ± 7.8 mV. Treatment of cardiac fibroblasts with NPCNP increased cyclic guanosine-monophosphate (cGMP) synthesis, confirming that exogenous CNP delivered via oligo-urethane NPs is bioactive and can induce downstream signaling that has been implicated in antagonizing transforming growth factor-ß1 (TGF-ß1)-induced myofibrogenic differentiation. It is also shown that treatment with NPCNP attenuated contraction of collagen gels by cardiac myofibroblasts stimulated with TGF-ß1. Coating with heparin on the NPCNP (HEP-NPCNP) exemplified an approach to extend the release of CNP from the NPs. Both HEP-NPCNP and NPCNP show minimal cell toxicity, studied up to 0.25 × 1010 NPs/mL in culture media. These findings support further investigation of CNP delivery via NPs as a future therapy for suppressing cardiac fibrosis.

Interaction of fibroblasts and induced pluripotent stem cells with poly(vinyl alcohol)-based hydrogel substrates.

Induced pluripotent stem cells (iPSCs) provide a promising means of creating custom-tailored cell lines for cellular therapies. Their application in regenerative medicine, however, depends on the possibility that the maintenance and differentiation of cells and organs occur under defined conditions. One major component of stem cell culture systems is the substrate, where the cells must attach and proliferate. The present study aimed to investigate the putative cytotoxic effects of poly(vinyl alcohol) (PVA)-based matrices on the in vitro culture of mouse fetal fibroblasts. In addition, the PVA-based hydrogels were used to determine the capacity of bovine induced pluripotent stem cells (biPSCs) to adhere and proliferate on synthetic substrates. Our results show that both cell types interacted with the substrate and presented proliferation during culture. The biPSCs formed new colonies when cell suspensions were placed onto the hydrogel surface for culture. These results may represent a new characterized xeno-free clinical grade culture system to be widely applied in cell-based therapies.

Electrospinning and electrospray of bio-based and natural polymers for biomaterials development.

Over nearly 70 years, polymers have revolutionized the global economy, manufacturing and, mainly, the fields which require biocompatible materials, as food technology and packaging, controlled drug delivery, tissue engineering, regenerative medicine, wound dressing, anti-allergy textiles, and personal care. While new high-performance polymers were produced from fossil-based sources to meet the functional performance demands of new applications, Earth has been polluted by the operation of factories that released CO2 to the atmosphere during the production of synthetic polymers. At the same time, biocompatible and biodegradable alternatives were being required to meet specific needs of a range of applications. In this paper, we reviewed the use of electrospun/electrospray bio-based and natural polymers in the last ten years in food technology and smart packaging, food additives, antimicrobial packaging, enzyme immobilization, tissue engineering, drug delivery, wound dressing, anti-allergy fibers from milk, and faux meat. Also, we reviewed the use of ionic liquids and click chemistry techniques as alternatives for modification and functionalization of electrospun/electrospray bio-based and natural polymers.

Poly (lactic acid)/chitosan fiber mats: investigation of effects of the support on lipase immobilization.

The greatest challenge for biotechnological processes is to have immobilized enzymes acting as good green catalysts with high reusability rates. In this work, we have produced electrospun fibers from poly (lactic acid)/chitosan blends. Further, we evaluated the influence of these materials as support for lipase immobilization. The PLA/chitosan fiber mats were composed by non-woven nanofibers, with diameters ranging from 200 nm to 1.3 µm. The solvent (TFA) as well as the chitosan addition influenced morphology, hydrophobicity and mechanical properties of PLA nanofibers. It was observed that even for lower concentration of lipase (5 U) higher enzyme activity retention was detected in the PLA/chitosan blends. In addition, a remarkable improvement of lipase activity on pure PLA fiber mat was verified, indicating that most of the enzymes were probably in their active form.

Gelatin and galactomannan-based scaffolds: Characterization and potential for tissue engineering applications.

In this work, we produced gelatin films containing different concentrations of galactomannan by casting solutions. The films were crosslinked by immersion in 30mM solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC). The crosslinking of gelatin-containing films was confirmed by the reduction of free amine band intensity (3400-3200cm(-1)) in the GEL IR, as well as by the evaluation of its behavior when immersed in phosphate-buffer solution. The crosslinking of galactomannan film was confirmed by the formation of new ether bonds, as observed by increasing intensity of the band at 1148cm(-1), and the reduction of OH band intensity (3600-3200cm(-1)). The presence of galactomannan and the crosslinking mediated by EDC were responsible to improve elasticity in the gelatin-based films. The samples did not show cytotoxicity during 24h or 48h. In addition, rat mesenchymal stem cells adhered to the films regardless of galactomannan concentration. The results indicated that the gelatin/galactomannan films are potential biomaterials for use as scaffolds for tissue engineering.