Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to ...achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.
Display omitted
•Porphyrins are emerging as key materials in the several energy conversion systems.•Porphyrins in photovoltaic convert light to electrical energy.•Porphyrins in photocatalyst convert ...light to chemical energy.•Porphyrins in energy storage system reversible convert chemical to electrical energy.
Porphyrins are composed of four pyrrolic subunits interconnected via methine bridges to form fully conjugated 18 π electron-containing aromatic macrocycles. This macrocyclic aromatic compound has various interesting optical, electrical and physicochemical properties. Because of their unique features, it is possible for the porphyrin derivatives to reversibly convert photo, electrical and chemical energy, which lead them to be the key materials in energy conversion systems. In photovoltaics, the porphyrin derivatives generate electrical energy via absorbing light energy. They also serve as photocatalyst to convert light to chemical energy. Moreover, they play a role in electrode of the energy storage systems due to their unique electrochemical redox properties. In this paper, emerging development in terms of porphyrin-based energy conversion systems will be review. This review is divided into three sections focusing on porphyrin-based energy conversion technologies for (i) photovoltaics, (ii) photocatalysts and (iii) energy storage systems, respectively.
Conspectus Porphyrin derivatives are ubiquitous in nature and have important biological roles, such as in light harvesting, oxygen transport, and catalysis. Owing to their intrinsic π-conjugated ...structure, porphyrin derivatives exhibit characteristic photophysical and electrochemical properties. In biological systems, porphyrin derivatives are associated with various protein molecules through noncovalent interactions. For example, hemoglobin, which is responsible for oxygen transport in most vertebrates, consists of four subunits of a globular protein with an iron porphyrin derivative prosthetic group. Furthermore, noncovalently arranged porphyrin derivatives are the fundamental chromophores in light-harvesting systems for photosynthesis in plants and algae. These biologically important roles originate from the functional versatility of porphyrin derivatives. Specifically, porphyrins are excellent host compounds, forming coordination complexes with various metal ions that adds functionality to the porphyrin unit, such as redox activity and additional ligand binding at the central metal ion. In addition, porphyrins are useful building blocks for functional supramolecular assemblies because of their flat and symmetrical molecular architectures, and their excellent photophysical properties are typically utilized for the fabrication of bioactive functional materials. In this Account, we summarize our endeavors over the past decade to develop functional materials based on porphyrin derivatives using bioinspired approaches. In the first section, we discuss several synthetic receptors that act as artificial allosteric host systems and can be used for the selective detection of various chemicals, such as cyanide, chloride, and amino acids. In the second section, we introduce multiporphyrin arrays as mimics of natural light-harvesting complexes. The active control of energy transfer processes by additional guest binding and the fabrication of organic photovoltaic devices using porphyrin derivatives are also introduced. In the third section, we introduce several types of porphyrin-based supramolecular assemblies. Through noncovalent interactions such as metal–ligand interaction, hydrogen bonding, and π–π interaction, porphyrin derivatives were constructed as supramolecular polymers with formation of fiber or toroidal assembly. In the last section, the application of porphyrin derivatives for biomedical nanodevice fabrication is introduced. Even though porphyrins were good candidates as photosensitizers for photodynamic therapy, they have limitations for biomedical application owing to aggregation in aqueous media. We suggested ionic dendrimer porphyrins and they showed excellent photodynamic therapy (PDT) efficacy.
As the main precursor of cardiovascular diseases, atherosclerosis is a complex inflammatory disorder that preferentially occurs in stenotic, curved, and branched arterial regions. Although various in ...vitro models are established to understand its pathology, reconstructing the native atherosclerotic environment that involves both co‐cultured cells and local turbulent flow singling remains challenging. This study develops an arterial construct via in‐bath coaxial cell printing that not only facilitates the direct fabrication of three‐layered conduits with tunable geometry and dimensions but also maintains structural stability. Functional vascular tissues, which respond to various stimulations that induce endothelial dysfunction, are rapidly generated in the constructed models. The presence of multiple vascular tissues under stenotic and tortuous turbulent flows allows the recapitulation of hallmark events in early atherosclerosis under physiological conditions. Furthermore, the fabricated models are utilized to investigate the individual and synergistic functions of cell co‐culture and local turbulent flows in regulating atherosclerotic initiation, as well as the dose‐dependent therapeutic effect of atorvastatin. These outcomes suggest that the constructed atherosclerotic model via a novel fabrication strategy is a promising platform to elucidate the pathophysiology of atherosclerosis and seek effective drugs and therapies.
An advanced in vitro atherosclerosis model that enables the co‐culture of multiple vascular cells under local turbulent flows is developed from geometry‐tunable arterial constructs engineered by a novel in‐bath coaxial cell printing strategy. This platform recapitulates the hallmark events in early atherosclerosis and shows great potential for understanding the atherosclerotic pathophysiology and evaluating drug efficacy.
Abstract
5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective ...clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes
WNT3
transcription, leading to activation of the WNT/β-catenin pathway in
Apc
Min/+
/Lgr5
EGFP
mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.
Building human tissues via 3D cell printing technology has received particular attention due to its process flexibility and versatility. This technology enables the recapitulation of unique features ...of human tissues and the all-in-one manufacturing process through the design of smart and advanced biomaterials and proper polymerization techniques. For the optimal engineering of tissues, a higher-order assembly of physiological components, including cells, biomaterials, and biomolecules, should meet the critical requirements for tissue morphogenesis and vascularization. The convergence of 3D cell printing with a microfluidic approach has led to a significant leap in the vascularization of engineering tissues. In addition, recent cutting-edge technology in stem cells and genetic engineering can potentially be adapted to the 3D tissue fabrication technique, and it has great potential to shift the paradigm of disease modeling and the study of unknown disease mechanisms required for precision medicine. This review gives an overview of recent developments in 3D cell printing and bioinks and provides technical requirements for engineering human tissues. Finally, we propose suggestions on the development of next-generation therapeutics and diagnostics.
The musculoskeletal system is a vital body system that protects internal organs, supports locomotion, and maintains homeostatic function. Unfortunately, musculoskeletal disorders are the leading ...cause of disability worldwide. Although implant surgeries using autografts, allografts, and xenografts have been conducted, several adverse effects, including donor site morbidity and immunoreaction, exist. To overcome these limitations, various biomedical engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissue. In this review, the leading edge of musculoskeletal tissue engineering using 3D bioprinting technology and musculoskeletal tissue-derived decellularized extracellular matrix bioink is described. In particular, studies on in vivo regeneration and in vitro modeling of musculoskeletal tissue have been focused on. Lastly, the current breakthroughs, limitations, and future perspectives are described.
3D cell-printing technique has been under spotlight as an appealing biofabrication platform due to its ability to precisely pattern living cells in pre-defined spatial locations. In skin tissue ...engineering, a major remaining challenge is to seek for a suitable source of bioink capable of supporting and stimulating printed cells for tissue development. However, current bioinks for skin printing rely on homogeneous biomaterials, which has several shortcomings such as insufficient mechanical properties and recapitulation of microenvironment. In this study, we investigated the capability of skin-derived extracellular matrix (S-dECM) bioink for 3D cell printing-based skin tissue engineering. S-dECM was for the first time formulated as a printable material and retained the major ECM compositions of skin as well as favorable growth factors and cytokines. This bioink was used to print a full thickness 3D human skin model. The matured 3D cell-printed skin tissue using S-dECM bioink was stabilized with minimal shrinkage, whereas the collagen-based skin tissue was significantly contracted during in vitro tissue culture. This physical stabilization and the tissue-specific microenvironment from our bioink improved epidermal organization, dermal ECM secretion, and barrier function. We further used this bioink to print 3D pre-vascularized skin patch able to promote in vivo wound healing. In vivo results revealed that endothelial progenitor cells (EPCs)-laden 3D-printed skin patch together with adipose-derived stem cells (ASCs) accelerates wound closure, re-epithelization, and neovascularization as well as blood flow. We envision that the results of this paper can provide an insightful step towards the next generation source for bioink manufacturing.
Engineered skeletal muscle tissues that mimic the structure and function of native muscle have been considered as an alternative strategy for the treatment of various muscular diseases and injuries. ...Here, it is demonstrated that 3D cell‐printing of decellularized skeletal muscle extracellular matrix (mdECM)‐based bioink facilitates the fabrication of functional skeletal muscle constructs. The cellular alignment and the shape of the tissue constructs are controlled by 3D cell‐printing technology. mdECM bioink provides the 3D cell‐printed muscle constructs with a myogenic environment that supports high viability and contractility as well as myotube formation, differentiation, and maturation. More interestingly, the preservation of agrin is confirmed in the mdECM, and significant increases in the formation of acetylcholine receptor clusters are exhibited in the 3D cell‐printed muscle constructs. In conclusion, mdECM bioink and 3D cell‐printing technology facilitate the mimicking of both the structural and functional properties of native muscle and hold great promise for producing clinically relevant engineered muscle for the treatment of muscular injuries.
Skeletal muscle‐derived bioink with 3D cell‐printing technology facilitates the fabrication of 3D functional muscle constructs. 3D cell‐printing technology can generate various types of constructs and cellular alignments in a controlled manner. The bioink retains the major extracellular matrix molecules that provide a microenvironment similar to that of native muscle and induce myogenesis in 3D cell‐printed muscle constructs.
Advanced maternal age (AMA) is a growing trend world-wide and is traditionally defined as childbearing in women over 35 years of age. The purpose of our study was to determine the maternal age group ...within the Korean population, in which the risk of early neonatal mortality is increased. Korean birth and mortality data from 2011 to 2015 were used to estimate the influence of maternal age on the risk of early neonatal mortality. A Poisson regression was used for the analysis of multiple clinical variables such as year of delivery, maternal age, gestational age, infant gender, birth weight, multiple birth, parity, and socioeconomic variables. Furthermore, a generalized additive model was used to determine the maternal age at which the risk for neonatal mortality increases. We included 2,161,908 participants and found that 49.4% of mothers were 30-34 years of age at delivery. The proportion of mothers aged 35 and above increased over the 5-year analysis period. A maternal age lower than 29 years or higher than 40 years was associated with a relatively higher risk of early neonatal mortality. The trend and magnitude of the age-related risk on early neonatal mortality were independent of maternal socioeconomic factors such as living in an obstetrically underserved area, education level, and employment status. Furthermore, we showed that the risk for early neonatal mortality was higher until the maternal age of 28. However, there were no significant changes in the risk between the age of 35 and 40 years. According to recent national-wide data, age-related risk for early neonatal mortality is only apparent for mothers ≥ 40 years old whereas, age between 35 and 39 are not at increased risk for early neonatal mortality, despite being classified as AMA.
PDF
