Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in ...cell‐based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio‐blood‐vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular‐tissue‐derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin‐loaded poly(lactic‐co‐glycolic) acid microspheres. The therapeutic efficacy of cell/drug‐laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D‐printed ECM‐mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.
The extracellular matrix of vascular tissue is formulated as a bioink to engineer a bioinspired blood vessel using the 3D coaxial cell printing technique. Carrying progenitor cells and proangiogenic drugs, the transplanted construct exhibits remarkable therapeutic efficacy for ischemic diseases.
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.
Tissue engineering requires not only tissue‐specific functionality but also a realistic scale. Decellularized extracellular matrix (dECM) is presently applied to the extrusion‐based 3D printing ...technology. It has demonstrated excellent efficiency as bioscaffolds that allow engineering of living constructs with elaborate microarchitectures as well as the tissue‐specific biochemical milieu of target tissues and organs. However, dECM bioinks have poor printability and physical properties, resulting in limited shape fidelity and scalability. In this study, new light‐activated dECM bioinks with ruthenium/sodium persulfate (dERS) are introduced. The materials can be polymerized via a dityrosine‐based cross‐linking system with rapid reaction kinetics and improved mechanical properties. Complicated constructs with high aspect ratios can be fabricated similar to the geometry of the desired constructs with increased shape fidelity and excellent printing versatility using dERS. Furthermore, living tissue constructs can be safely fabricated with excellent tissue regenerative capacity identical to that of pure dECM. dERS may serve as a platform for a wider biofabrication window through building complex and centimeter‐scale living constructs as well as supporting tissue‐specific performances to encapsulated cells. This capability of dERS opens new avenues for upscaling the production of hydrogel‐based constructs without additional materials and processes, applicable in tissue engineering and regenerative medicine.
New light‐activated decellularized extracellular bioinks with ruthenium/sodium persulfate (dERS) are cured through a rapid dityrosine‐based cross‐linking reaction. dERS enables the bioprinting of complex structures with increased shape fidelity and highly improved printing versatility. The cell‐laden constructs also exhibit excellent tissue regenerative capacity. These capabilities of dERS open new avenues for the production of clinically relevant soft tissues applicable in tissue engineering field.
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.
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.
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.
The liver is an important organ and plays major roles in the human body. Because of the lack of liver donors after liver failure and drug-induced liver injury, much research has focused on developing ...liver alternatives and liver in vitro models for transplantation and drug screening. Although numerous studies have been conducted, these systems cannot faithfully mimic the complexity of the liver. Recently, three-dimensional (3D) cell printing technology has emerged as one of a number of innovative technologies that may help to overcome this limitation. However, a great deal of work in developing biomaterials optimized for 3D cell printing-based liver tissue engineering remains. Therefore, in this work, we developed a liver decellularized extracellular matrix (dECM) bioink for 3D cell printing applications and evaluated its characteristics. The liver dECM bioink retained the major ECM components of the liver while cellular components were effectively removed and further exhibited suitable and adjustable properties for 3D cell printing. We further studied printing parameters with the liver dECM bioink to verify the versatility and fidelity of the printing process. Stem cell differentiation and HepG2 cell functions in the liver dECM bioink in comparison to those of commercial collagen bioink were also evaluated, and the liver dECM bioink was found to induce stem cell differentiation and enhance HepG2 cell function. Consequently, the results demonstrate that the proposed liver dECM bioink is a promising bioink candidate for 3D cell printing-based liver tissue engineering.
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.
Display omitted
•Porphyrin derivatives serve as fluorescent chromophores to detect chemicals.•The coordination of metal ions to the porphyrin center provides Lewis acid sites.•Porphyrin derivatives ...act as signaling units for emission or absorption changes.
Porphyrins are heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges. Because of their unique properties, synthetic porphyrin derivatives are powerful tools for molecular recognition. The optical or electronic monitoring of porphyrin derivatives permits the detection of the binding of transition metals. The binding of the metal ion to the porphyrin center provides additional axial ligand binding sites, which can be utilized for molecular recognition and sensing. Because of the large extinction coefficient and emission property, porphyrin derivatives can be utilized as fluorescent chromophores for the detection of various chemicals. In this paper, important development in terms of porphyrin-based chemical probes will be reviewed. This review is divided into nine sections focusing on porphyrin-based probes for (i) cations, (ii) anions, (iii) ion pairs, (iv) volatile organic chemicals, (v) nitroaromatic compounds, (vi) gases, (vii), reactive oxygen species, (viii) chiral discrimination, and (ix) environmental change detection, respectively.
PDF
