The successful transplantation of stem cells has the potential to transform regenerative medicine approaches and open promising avenues to repair, replace, and regenerate diseased, damaged, or aged ...tissues. However, pre-/post-transplantation issues of poor cell survival, retention, cell fate regulation, and insufficient integration with host tissues constitute significant challenges. The success of stem cell transplantation depends upon the coordinated sequence of stem cell renewal, specific lineage differentiation, assembly, and maintenance of long-term function. Advances in biomaterials can improve pre-/post-transplantation outcomes by integrating biophysiochemical cues and emulating tissue microenvironments. This review highlights leading biomaterials-based approaches for enhancing stem cell transplantation.
The success of stem cell transplantation depends upon the coordinated sequence of stem cell renewal, differentiation, assembly, and maintenance of long-term function. Advances in biomaterials can improve pre-/post-transplantation outcomes by integrating biophysiochemical cues and emulating tissue microenvironments. This review highlights promising biomaterials-based approaches for enhancing stem cell transplantation.
After cardiovascular injury, numerous pathological processes adversely impact the homeostatic function of cardiomyocyte, macrophage, fibroblast, endothelial cell, and vascular smooth muscle cell ...populations. Subsequent malfunctioning of these cells may further contribute to cardiovascular disease onset and progression. By modulating cellular responses after injury, it is possible to create local environments that promote wound healing and tissue repair mechanisms. The extracellular matrix continuously provides these mechanosensitive cell types with physical cues spanning the micro- and nanoscale to influence behaviors such as adhesion, morphology, and phenotype. It is therefore becoming increasingly compelling to harness these cell–substrate interactions to elicit more native cell behaviors that impede cardiovascular disease progression and enhance regenerative potential. This review discusses recent in vitro and preclinical work that have demonstrated the therapeutic implications of micro- and nanoscale biophysical cues on cell types adversely affected in cardiovascular diseases — cardiomyocytes, macrophages, fibroblasts, endothelial cells, and vascular smooth muscle cells.
Micro- and nanoscale topographies that mimic biophysical cues observed in native tissue architectures can be used to modulate pathological behaviors of adversely impacted cell types involved in cardiovascular diseases – cardiomyocytes, macrophages, fibroblasts, endothelial cells, and vascular smooth muscle cells – to promote wound healing and tissue repair mechanisms. Display omitted
Micro and nanoscale drug carriers must navigate through a plethora of dynamic biological systems prior to reaching their tissue or disease targets. The biological obstacles to drug delivery come in ...many forms and include tissue barriers, mucus and bacterial biofilm hydrogels, the immune system, and cellular uptake and intracellular trafficking. The biointerface of drug carriers influences how these carriers navigate and overcome biological barriers for successful drug delivery. In this review, we examine how key material design parameters lead to dynamic biointerfaces and improved drug delivery across biological barriers. We provide a brief overview of approaches used to engineer key physicochemical properties of drug carriers, such as morphology, surface chemistry, and topography, as well as the development of dynamic responsive materials for barrier navigation. We then discuss essential biological barriers and how biointerface engineering can enable drug carriers to better navigate and overcome these barriers to drug delivery.
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Nanoparticulate composites of hydroxyapatite (HAp) and chitosan were synthesized by ultrasound-assisted sequential precipitation and characterized for their microstructure at the atomic scale, ...surface charge, drug release properties, and combined antibacterial and osteogenic response. Crystallinity of HAp nanoparticles was reduced because of the interference of the surface layers of chitosan with the dissolution/reprecipitation-mediated recrystallization mechanism that conditions the transition from the as-precipitated amorphous calcium phosphate phase to the most thermodynamically stable one—HAp. Embedment of 5–10 nm sized, narrowly dispersed HAp nanoparticles within the polymeric matrix mitigated the burst release of the small molecule model drug, fluorescein, bound to HAp by physisorption, and promoted sustained-release kinetics throughout the 3 weeks of release time. The addition of chitosan to the particulate drug carrier formulation, however, reduced the antibacterial efficacy against Saureus. Excellent cell spreading and proliferation of osteoblastic MC3T3-E1 cells evidenced on microscopic conglomerates of HAp nanoparticles in vitro also markedly diminished on HAp/chitosan composites. Mitochondrial dehydrogenase activity exhibited normal values only for HAp/chitosan particle concentrations of up to 2 mg/cm2 and significantly dropped, by about 50%, at higher particle concentrations (4 and 8 mg/cm2). The gene expression of osteocalcin, a mineralization inductor, and the transcription factor Runx2 was downregulated in cells incubated in the presence of 3 mg/cm2 HAp/chitosan composite particles, whereas the expression of osteopontin, a potent mineralization inhibitor, was upregulated, further demonstrating the partially unfavorable osteoblastic cell response to the given particles. The peak in the expression of osteogenic markers paralleling the osteoblastic differentiation was also delayed most for the cell population incubated with HAp/chitosan particles. Overall, the positive effect of chitosan coating on the drug elution profile of HAp nanoparticles as carriers for the controlled delivery of antibiotics in the treatment of osteomyelitis was compensated for by the lower bacteriostatic efficiency and the comparatively unviable cell response to the composite material, especially at higher dosages.
Diabetes Mellitus is a group of diseases characterized by high blood glucose levels due to patients' inability to produce sufficient insulin. Current interventions often require implants that can ...detect and correct high blood glucose levels with minimal patient intervention. However, these implantable technologies have not reached their full potential in vivo due to the foreign body response and subsequent development of fibrosis. Therefore, for long-term function of implants, modulating the initial immune response is crucial in preventing the activation and progression of the immune cascade. This review discusses the different molecular mechanisms and cellular interactions involved in the activation and progression of foreign body response (FBR) and fibrosis, specifically for implants used in diabetes. We also highlight the various strategies and techniques that have been used for immunomodulation and prevention of fibrosis. We investigate how these general strategies have been applied to implants used for the treatment of diabetes, offering insights on how these devices can be further modified to circumvent FBR and fibrosis.
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•We highlight polymeric materials used for long-acting intraocular drug delivery.•We discuss design considerations for delivering small molecules and biologics.•We describe devices currently in the ...market and the commercialization pipeline.•We highlight the need for the intraocular sustained delivery of biologics.
Topical eye-drop administration and intravitreal injections are the current standard for ocular drug delivery. However, patient adherence to the drug regimen and insufficient administration frequency are well-documented challenges to this field. In this review, we describe recent advances in intraocular implants designed to deliver therapeutics for months to years, to obviate the issues of patient adherence. We highlight recent advances in monolithic ocular implants in the literature, the commercialization pipeline, and approved for the market. We also describe design considerations based on material selection, active pharmaceutical ingredient, and implantation site.
Nanotubes for drug release: Titania nanotubes (see image) fabricated by an easy anodization process can be used as drug‐eluting coatings for implantable devices. The release rate of the drugs is ...controlled by varying the amount of proteins loaded into the nanotubes. Moreover, by changing the nanotube diameter, wall thickness, and length, the release kinetics can be altered for each specific drug to achieve a sustained release.
Unresolved inflammation is central to the pathophysiology of commonly occurring vascular diseases such as atherosclerosis, aneurysm, and deep vein thrombosis - conditions that are responsible for ...considerable morbidity and mortality. Surgical or catheter-based procedures performed on affected blood vessels induce acute-on-chronic inflammatory responses. The resolution of vascular inflammation is an important driver of vessel wall remodeling and functional recovery in these clinical settings. Specialized pro-resolving lipid mediators (SPMs) derived from omega-3 polyunsaturated fatty acids orchestrate key cellular processes driving resolution and a return to homeostasis. The identification of their potent effects in classic animal models of sterile inflammation triggered interest in their vascular properties. Recent studies have demonstrated that SPMs are locally synthesized in vascular tissues, have direct effects on vascular cells and their interactions with leukocytes, and play a protective role in the injury response. Early translational work has established the potential for SPMs as vascular therapeutics, and as candidate biomarkers in vascular disease. Further investigations are needed to understand the molecular and cellular mechanisms of resolution in the vasculature, to improve tools for clinical measurement, and to better define the potential for "resolution therapeutics" in vascular patients.
The ability to precisely treat human disease is facilitated by the sophisticated design of pharmacologic agents. Nanotechnology has emerged as a valuable approach to creating vehicles that can ...specifically target organ systems, effectively traverse epithelial barriers, and protect agents from premature degradation. In this review, we discuss the molecular basis for epithelial barrier function, focusing on tight junctions, and describe different pathways that drugs can use to cross barrier-forming tissue, including the paracellular route and transcytosis. Unique features of drug delivery applied to different organ systems are addressed: transdermal, ocular, pulmonary, and oral delivery. We also discuss how design elements of different nanoscale systems, such as composition and nanostructured architecture, can be used to specifically enhance transepithelial delivery. The ability to tailor nanoscale drug delivery vehicles to leverage epithelial barrier biology is an emerging theme in the pursuit of facilitating the efficacious delivery of pharmacologic agents.
Transplantation of islet or beta cells is seen as the cure for type 1 diabetes since it allows physiological regulation of blood glucose levels without requiring any compliance from the patients. In ...order to circumvent the use of immunosuppressive drugs (and their side effects), semipermeable membranes have been developed to encapsulate and immunoprotect transplanted cells. This review presents the historical developments of immunoisolation and provides an update on the current research in this field. A particular emphasis is laid on the fabrication, characterization and performance of membranes developed for immunoisolation applications.
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