Nanofiber composites in biomolecular delivery
01 Jan 2017-pp 225-252
TL;DR: In this article, the authors describe the various ways of forming biomolecule composite nanofibers, associated characterization techniques, and different release mechanisms with the focus on composite and nanoparticles in biomolecular delivery.
Abstract: The advantage of nanomaterials in the biomedical field can be explored through the use of nanofibers designed using biocompatible and biodegradable polymers. Owing to their versatility and unique properties, nanofibers have attracted the biomedical community for their applications in tissue engineering, drug delivery, gene therapy, and cell therapy. For tissue engineering applications, nanofibers can be explored as scaffolds due to their potential to mimic the native extracellular matrix (ECM) collagen structure of the cell niche/microenvironment. In natural systems, the ECM not only provides the topographical cues but also offers various biochemical signals to regulate the cell’s fate and functions. Therefore, to completely mimic the natural microenvironment, these nanofibrous scaffolds needs to provide a critical signaling environment that can regulate the resident cell behavior and destiny. Composite nanofibers reinforced with various biomolecules like growth factors, cytokines, small molecules, etc. have recently emerged as a solution for completely mimicking the natural microenvironment. The unique advantages of nanofibers such as high surface area, interconnected pores, porosity, etc. have been explored for its use in the delivery of drug molecules, genes (RNA, DNA), and living cells, for various biomedical applications. This chapter essentially describes the various ways of forming biomolecule composite nanofibers, associated characterization techniques, and different release mechanisms with the focus on composite nanofibers and nanoparticles in biomolecular delivery. For the benefit of readers, authors have briefly explained the applications of composite nanofibers as well as nanoparticles for the biomolecule delivery in different biomedical fields along with their clinical status and their future perspectives.
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TL;DR: In this article , the pH-sensitive anthocyanin compound was extracted from red cabbage and encapsulated with gelatin as the wall material at the nanoscale (350 nm) through electrospraying.
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TL;DR: Scientific evidence provided in this review verifies that the nanofiber niche provides an ideal mimic of the physical microenvironment of HSCs thereby offering great potential for clinical applications.
Abstract: This review summarizes current strategies in the development of advanced nanofibrous polymer-based scaffolds via electrospinning, their applications in mimicking the extracellular matrix, and the use of polymer nanofibers to deliver growth factors or small molecules for ex vivo expansion of HSCs. Hematopoietic stem cell (HSC) transplantation has become the standard of care for patients with hematologic cancers, anemia, and a variety of other malignant and non-malignant disorders. Although mobilized peripheral blood (MPB) has become a preferred source of HSCs for transplants, bone marrow (BM) and umbilical cord blood (UCB) are also frequently utilized. Regardless of source, Regardless of source, HSC transplantation suffers from low cell doses. Therefore, methods to increase the cell dose while maintaining the progenitor phenotype, especially the CD34+ progenitor cells, would have a significant clinical impact. Ex vivo expansion of HSCs prior to transplantation is one approach that offers tremendous promise for increasing cell doses and improving clinical outcomes. Many ex vivo strategies have been developed within the last decade in order to address the issue of low cell dose, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Here, we report the current progress of nanofibrous scaffolds for the ex vivo expansion of hematopoietic stem cells (HSCs). In this review, we present the technique of electrospinning for nanofibrous scaffolds, focusing mainly on preparation methods, materials (synthetic, natural, and hybrid polymers), and surface-structural modifications. The variables of nanofiber processing parameters and its impact on the nanofiber assembly is reported as well as the effect of the solution parameters on the structural morphology of the fabricated nanofibers. Critical features of fabricated nanofibers such as porous structure and high specific surface area are addressed, but more importantly the necessity of mimicking the intrinsic properties of the native in vivo microenvironment of the extracellular matrix (ECM). Researchers have been largely successful in replicating the diverse nature of the ECM through the incorporation of small molecules, growth factors, and signaling molecules into 3D scaffolds to generate biomimetic hierarchical structures. Harnessing the potential of the stem cell niche forms the basis of clinical therapy in the ex vivo expansion of cord blood-derived hematopoietic stem cells. As reviewed in this article, advances in nanofiber ex vivo approaches based upon emerging biomaterials opens new doors for artificial niches. Scientific evidence provided in this review verifies that the nanofiber niche provides an ideal mimic of the physical microenvironment of HSCs thereby offering great potential for clinical applications.
01 Apr 2022
TL;DR: Commonly available treatments for scar prevention or reduction, such as stem cell therapy or surgical approaches, are limited in reaching a satisfying result and drive the need for advanced progress in the field of drug delivery.
Abstract: The importance of developing anti-scar wound dressing comes from the fact that scar as an abnormal tissue affects aesthetics and changes the functionality of tissue strength and pliability[1]. The main group of patients who are at risk of scar formation is burn survivors. The World Health Organization (WHO) reports that annually 11 million people suffer from severe burn wounds that need medical care [2]–[6]. Burn scar has devastating effects, including pain, intolerance of heat, severe itching, limitations in movement, and dyspigmentation; these factors lead to problems with social integration [7] and discrimination in the community [8] which can reduce the burn survivors' quality of life. Commonly available treatments for scar prevention or reduction, such as stem cell therapy or surgical approaches, are limited in reaching a satisfying result. These limits drive the need for advanced progress in the field of drug delivery. Numerous studies have been published on developing anti-scar wound dressings; nevertheless, a clinical product has not been produced yet.
References
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TL;DR: The extracellular matrix is the non-cellular component present within all tissues and organs, and provides not only essential physical scaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue development.
Abstract: ![Figure][1]
The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, and provides not only essential physical scaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue
3,190 citations
TL;DR: Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.
Abstract: New blood vessel formation (angiogenesis) is a fundamental event in the process of tumor growth and metastatic dissemination. Hence, the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research. The vascular endothelial growth factor (VEGF) pathway is well established as one of the key regulators of this process. The VEGF/ VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities, cell-type expression, and function. Activation of the VEGF-receptor pathway triggers a network of signaling processes that promote endothelial cell growth, migration, and survival from pre-existing vasculature. In addition, VEGF mediates vessel permeability, and has been associated with malignant effusions. More recently, an important role for VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant sites of neovascularization. The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational design and development of agents that selectively target this pathway. Studies with various anti-VEGF/VEGF-receptor therapies have shown that these agents can potently inhibit angiogenesis and tumor growth in preclinical models. Recently, an anti-VEGF antibody (bevacizumab), when used in combination with chemotherapy, was shown to significantly improve survival and response rates in patients with metastatic colorectal cancer and thus, validate VEGF pathway inhibitors as an important new treatment modality in cancer therapy.
2,699 citations
TL;DR: It is concluded that differential VEGF-A isoform localization in the extracellular space provides a control point for regulating vascular branching pattern.
Abstract: Branching morphogenesis in the mammalian lung and Drosophila trachea relies on the precise localization of secreted modulators of epithelial growth to select branch sites and direct branch elongation, but the intercellular signals that control blood vessel branching have not been previously identified. We found that VEGF(120/120) mouse embryos, engineered to express solely an isoform of VEGF-A that lacks heparin-binding, and therefore extracellular matrix interaction domains, exhibited a specific decrease in capillary branch formation. This defect was not caused by isoform-specific differences in stimulating endothelial cell proliferation or by impaired isoform-specific signaling through the Nrp1 receptor. Rather, changes in the extracellular localization of VEGF-A in heparin-binding mutant embryos resulted in an altered distribution of endothelial cells within the growing vasculature. Instead of being recruited into additional branches, nascent endothelial cells were preferentially integrated within existing vessels to increase lumen caliber. The disruption of the normal VEGF-A concentration gradient also impaired the directed extension of endothelial cell filopodia, suggesting that heparin-binding VEGF-A isoforms normally provide spatially restricted stimulatory cues that polarize and thereby guide sprouting endothelial cells to initiate vascular branch formation. Consistent with this idea, we found opposing defects in embryos harboring only a heparin-binding isoform of VEGF-A, including excess endothelial filopodia and abnormally thin vessel branches in ectopic sites. We conclude that differential VEGF-A isoform localization in the extracellular space provides a control point for regulating vascular branching pattern.
922 citations
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Abstract: Inflammation is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines. Inflammatory cytokines can be divided into two groups: those involved in acute inflammation and those responsible for chronic inflammation. This review describes the role played in acute inflammation by IL-1, TNF-alpha, IL-6, IL-11, IL-8 and other chemokines, G-CSF, and GM-CSF. It also describes the involvement of cytokines in chronic inflammation. This latter group can be subdivided into cytokines mediating humoral responses such as IL-4, IL-5, IL-6, IL-7, and IL-13, and those mediating cellular responses such as IL-1, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, interferons, transforming growth factor-beta, and tumor necrosis factor alpha and beta. Some cytokines, such as IL-1, significantly contribute to both acute and chronic inflammation. This review also summarizes features of the cell-surface receptors that mediate the inflammatory effects of the described cytokines.
899 citations
TL;DR: This work represents the first successful demonstration of plasmid DNA incorporation into a polymer scaffold using electrospinning, and when tested under tensile loads, the electrospun polymer/DNA composite scaffolds exhibited tensile moduli values that approximate those of skin and cartilage.
793 citations