Natalia Carballo-Pedrares

Bio: Natalia Carballo-Pedrares is an academic researcher. The author has contributed to research in topics: Gene delivery & Niosome. The author has an hindex of 3, co-authored 4 publications receiving 19 citations.

Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules.

Abstract: A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields.

Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches—An Overview

Abstract: Hydrogel-based nonviral gene delivery constitutes a powerful strategy in various regenerative medicine scenarios, as those concerning the treatment of musculoskeletal, cardiovascular, or neural tissues disorders as well as wound healing. By a minimally invasive administration, these systems can provide a spatially and temporarily defined supply of specific gene sequences into the target tissue cells that are overexpressing or silencing the original gene, which can promote natural repairing mechanisms to achieve the desired effect. In the present work, we provide an overview of the most avant-garde approaches using various hydrogels systems for controlled delivery of therapeutic nucleic acid molecules in different regenerative medicine approaches.

Scaffold-Mediated Gene Delivery for Osteochondral Repair.

Abstract: Osteochondral defects involve both the articular cartilage and the underlying subchondral bone. If left untreated, they may lead to osteoarthritis. Advanced biomaterial-guided delivery of gene vectors has recently emerged as an attractive therapeutic concept for osteochondral repair. The goal of this review is to provide an overview of the variety of biomaterials employed as nonviral or viral gene carriers for osteochondral repair approaches both in vitro and in vivo, including hydrogels, solid scaffolds, and hybrid materials. The data show that a site-specific delivery of therapeutic gene vectors in the context of acellular or cellular strategies allows for a spatial and temporal control of osteochondral neotissue composition in vitro. In vivo, implantation of acellular hydrogels loaded with nonviral or viral vectors has been reported to significantly improve osteochondral repair in translational defect models. These advances support the concept of scaffold-mediated gene delivery for osteochondral repair.

Chondrogenic Differentiation of Human Mesenchymal Stem Cells via SOX9 Delivery in Cationic Niosomes

Abstract: Gene transfer to mesenchymal stem cells constitutes a powerful approach to promote their differentiation into the appropriate cartilage phenotype. Although viral vectors represent gold standard vehicles, because of their high efficiency, their use is precluded by important concerns including an elevated immunogenicity and the possibility of insertional mutagenesis. Therefore, the development of new and efficient non-viral vectors is under active investigation. In the present study, we developed new non-viral carriers based on niosomes to promote the effective chondrogenesis of human MSCs. Two different niosome formulations were prepared by varying their composition on non-ionic surfactant, polysorbate 80 solely (P80), or combined with poloxamer 407 (P80PX). The best niosome formulation was proven to transfer a plasmid, encoding for the potent chondrogenic transcription factor SOX9 in hMSC aggregate cultures. Transfection of hMSC aggregates via nioplexes resulted in an increased chondrogenic differentiation with reduced hypertrophy. These results highlight the potential of niosome formulations for gene therapy approaches focused on cartilage repair.

Gene therapy approaches to regenerating the musculoskeletal system

Abstract: Injuries to the musculoskeletal system are common, debilitating and expensive. In many cases, healing is imperfect, which leads to chronic impairment. Gene transfer might improve repair and regeneration at sites of injury by enabling the local, sustained and potentially regulated expression of therapeutic gene products; such products include morphogens, growth factors and anti-inflammatory agents. Proteins produced endogenously as a result of gene transfer are nascent molecules that have undergone post-translational modification. In addition, gene transfer offers particular advantages for the delivery of products with an intracellular site of action, such as transcription factors and noncoding RNAs, and proteins that need to be inserted into a cell compartment, such as a membrane. Transgenes can be delivered by viral or nonviral vectors via in vivo or ex vivo protocols using progenitor or differentiated cells. The first gene transfer clinical trials for osteoarthritis and cartilage repair have already been completed. Various bone-healing protocols are at an advanced stage of development, including studies with large animals that could lead to human trials. Other applications in the repair and regeneration of skeletal muscle, intervertebral disc, meniscus, ligament and tendon are in preclinical development. In addition to scientific, medical and safety considerations, clinical translation is constrained by social, financial and logistical issues.

The biological applications of DNA nanomaterials: current challenges and future directions

Abstract: DNA, a genetic material, has been employed in different scientific directions for various biological applications as driven by DNA nanotechnology in the past decades, including tissue regeneration, disease prevention, inflammation inhibition, bioimaging, biosensing, diagnosis, antitumor drug delivery, and therapeutics. With the rapid progress in DNA nanotechnology, multitudinous DNA nanomaterials have been designed with different shape and size based on the classic Watson-Crick base-pairing for molecular self-assembly. Some DNA materials could functionally change cell biological behaviors, such as cell migration, cell proliferation, cell differentiation, autophagy, and anti-inflammatory effects. Some single-stranded DNAs (ssDNAs) or RNAs with secondary structures via self-pairing, named aptamer, possess the ability of targeting, which are selected by systematic evolution of ligands by exponential enrichment (SELEX) and applied for tumor targeted diagnosis and treatment. Some DNA nanomaterials with three-dimensional (3D) nanostructures and stable structures are investigated as drug carrier systems to delivery multiple antitumor medicine or gene therapeutic agents. While the functional DNA nanostructures have promoted the development of the DNA nanotechnology with innovative designs and preparation strategies, and also proved with great potential in the biological and medical use, there is still a long way to go for the eventual application of DNA materials in real life. Here in this review, we conducted a comprehensive survey of the structural development history of various DNA nanomaterials, introduced the principles of different DNA nanomaterials, summarized their biological applications in different fields, and discussed the current challenges and further directions that could help to achieve their applications in the future.

Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules.

Abstract: A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields.

Recent Advances of Stimuli-Responsive Polysaccharide Hydrogels in Delivery Systems: A Review.

Abstract: Hydrogels obtained from natural polymers have received widespread attention for their excellent biocompatible property, nontoxicity, easy gelation, and functionalization. Polysaccharides can regulate the gut microbiota and improve the intestinal microenvironment, thus exerting the healthy effect of intestinal immunity. In an active substance delivery system, the extent and speed of the substance reaching its target are highly dependent on the carrier. Thus, the smart active substance delivery systems are gradually increasing. The smart polysaccharide-hydrogels possess the ability in response to external stimuli through changing their volume phase and structure, which are applied in various fields. Natural polysaccharide-based hydrogels possess excellent characteristics of environmental friendliness, good biocompatibility, and abundant sources. According to the response type, natural polysaccharide-based hydrogels are usually divided into stimulus-responsive hydrogels, including internal response (pH, temperature, enzyme, redox) and external response (light, electricity, magnetism) hydrogels. The delivery system based on polysaccharides can exert their effects in the gastrointestinal tract. At the same time, polysaccharides may also take part in regulating the brain signals through the microbiota-gut-brain axis. Therefore, natural polysaccharide-hydrogels are considered as promising biomaterials, which can be designed as delivery systems for regulating the gut-brain axis. This article reviews the research advance of stimulus-responsive hydrogels, which focus on the types, response characteristics, and applications for polysaccharide-based smart hydrogels as delivery systems.