Wet 3D printing of biodegradable porous scaffolds to enable room-temperature deposition modeling of polymeric solutions for regeneration of articular cartilage.

Tissue engineering has emerged as an advanced strategy to regenerate various tissues using different raw materials, and thus it is desired to develop more approaches to fabricate tissue engineering scaffolds to fit specific yet very useful raw materials such as biodegradable aliphatic polyester like poly (lactide-co-glycolide) (PLGA). Herein, a technique of 'wet 3D printing' was developed based on a pneumatic extrusion three-dimensional (3D) printer after we introduced a solidification bath into a 3D printing system to fabricate porous scaffolds. The room-temperature deposition modeling of polymeric solutions enabled by our wet 3D printing method is particularly meaningful for aliphatic polyester, which otherwise degrades at high temperature in classic fuse deposition modeling. As demonstration, we fabricated a bilayered porous scaffold consisted of PLGA and its mixture with hydroxyapatite for regeneration of articular cartilage and subchondral bone. Long-termin vitroandin vivodegradation tests of the scaffolds were carried out up to 36 weeks, which support the three-stage degradation process of the polyester porous scaffold and suggest faster degradationin vivothanin vitro. Animal experiments in a rabbit model of articular cartilage injury were conducted. The efficacy of the scaffolds in cartilage regeneration was verified through histological analysis, micro-computed tomography (CT) and biomechanical tests, and the influence of scaffold structures (bilayerversussingle layer) onin vivotissue regeneration was examined. This study has illustrated that the wet 3D printing is an alternative approach to biofabricate tissue engineering porous scaffolds based on biodegradable polymers.

Electrospun Scaffolds are Not Necessarily Always Made of Nanofibers as Demonstrated by Polymeric Heart Valves for Tissue Engineering.

In the last 30 years, there are ≈60 000 publications about electrospun nanofibers, but it is still unclear whether nanoscale fibers are really necessary for electrospun tissue engineering scaffolds. The present report puts forward this argument and reveals that compared with electrospun nanofibers, microfibers with diameter of ≈3 µm (named as "oligo-micro fiber") are more appropriate for tissue engineering scaffolds owing to their better cell infiltration ability caused by larger pores with available nuclear deformation. To further increase pore sizes, electrospun poly(ε-caprolactone) (PCL) scaffolds are fabricated using latticed collectors with meshes. Fiber orientation leads to sufficient mechanical strength albeit increases porosity. The latticed scaffolds exhibit good biocompatibility and improve cell infiltration. Under aortic conditions in vitro, the performances of latticed scaffolds are satisfactory in terms of the acute systolic hemodynamic functionality, except for the higher regurgitation fraction caused by the enlarged pores. This hierarchical electrospun scaffold with sparse fibers in macropores and oligo-micro fibers in filaments provides new insights into the design of tissue engineering scaffolds, and tissue engineering may provide living heart valves with regenerative capabilities for patients with severe valve disease in the future.

Cooperative Photoredox and N-Heterocyclic Carbene Catalyzed Fluoroaroylation for the Synthesis of α-Trifluoromethyl-Substituted Ketones.

α-Trifluoromethylated ketones have attracted significant attention as valuable building blocks in organic synthesis. Such compounds are generally accessed through trifluoromethylation of ketones. Here we report an alternative disconnection approach for the construction of α-CF3 carbonyl compounds by using aroyl fluorides as bifunctional reagents for fluoroaroylation of gem-difluoroalkenes through cooperative photoredox and N-heterocyclic carbene (NHC) catalysis. This strategy bypasses the use of expensive or sensitive trifluoromethylation reagents and/or the requirement for ketone pre-functionalization, thus enabling an efficient and general synthetic method to access α-CF3 -substituted ketones. A wide variety of gem-difluoroalkenes and aroyl fluorides bearing a diverse set of functional groups are eligible substrates. Notably, the developed methodology also provides rapid access to mono- or difluoroalkyl ketones. Mechanistic studies reveal that merging photoredox catalysis with NHC catalysis is essential for the reaction.

Biaxial stretching of polytetrafluoroethylene in industrial scale to fabricate medical ePTFE membrane with node-fibril microstructure.

Expanded polytetrafluoroethylene (ePTFE) is promising in biomedical fields such as covered stents and plastic surgery owing to its excellent biocompatibility and mechanical properties. However, ePTFE material prepared by the traditional biaxial stretching process is with thicker middle and thinner sides due to the bowing effect, which poses a major problem in industrial-scale fabrication. To solve this problem, we design an olive-shaped winding roller to provide the middle part of the ePTFE tape with a greater longitudinal stretching amplitude than the two sides, so as to make up for the excessive longitudinal retraction tendency of the middle part when it is transversely stretched. The as-fabricated ePTFE membrane has, as designed, uniform thickness and node-fibril microstructure. In addition, we examine the effects of mass ratio of lubricant to PTFE powder, biaxial stretching ratio and sintering temperature on the performance of the resultant ePTFE membranes. Particularly, the relation between the internal microstructure of the ePTFE membrane and its mechanical properties is revealed. Besides stable mechanical properties, the sintered ePTFE membrane exhibits satisfactory biological properties. We make a series of biological assessments including in vitro hemolysis, coagulation, bacterial reverse mutation and in vivo thrombosis, intracutaneous reactivity test, pyrogen test and subchronic systemic toxicity test; all of the results meet the relevant international standards. The muscle implantation of the sintered ePTFE membrane into rabbits indicates acceptable inflammatory reactions of our sintered ePTFE membrane fabricated on industrial scale. Such a medical-grade raw material with the unique physical form and condensed-state microstructure is expected to afford an inert biomaterial potentially for stent-graft membrane.

Hierarchical helical carbon nanotube fibre as a bone-integrating anterior cruciate ligament replacement.

High rates of ligament damage require replacements; however, current synthetic materials have issues with bone integration leading to implant failure. Here we introduce an artificial ligament that has the required mechanical properties and can integrate with the host bone and restore movement in animals. The ligament is assembled from aligned carbon nanotubes formed into hierarchical helical fibres bearing nanometre and micrometre channels. Osseointegration of the artificial ligament is observed in an anterior cruciate ligament replacement model where clinical polymer controls showed bone resorption. A higher pull-out force is found after a 13-week implantation in rabbit and ovine models, and animals can run and jump normally. The long-term safety of the artificial ligament is demonstrated, and the pathways involved in integration are studied.

Quantitatively relating magnetic resonance T1 and T2 to glycosaminoglycan and collagen concentrations mediated by penetrated contrast agents and biomacromolecule-bound water.

Magnetic resonance imaging (MRI) is a promising non-invasive method to assess cartilage regeneration based on the quantitative relationship between MRI features and concentrations of the major components in the extracellular matrix (ECM). To this end, in vitro experiments are performed to investigate the relationship and reveal the underlying mechanism. A series of collagen (COL) and glycosaminoglycan (GAG) solutions at different concentrations are prepared, and T1 and T2 relaxation times are measured with or without a contrast agent (Gd-DTPA2-) by MRI. Fourier transform infrared spectrometry is also used to measure the contents of biomacromolecule-bound water and other water, allowing theoretical derivation of the relationship between biomacromolecules and the resulting T2 values. It has been revealed that the MRI signal in the biomacromolecule aqueous systems is mainly influenced by the protons in hydrogens of biomacromolecule-bound water, which we divide into inner-bound water and outer-bound water. We have also found that COL results in higher sensitivity of bound water than GAG in T2 mapping. Owing to the charge effect, GAG regulates the penetration of the contrast agent during dialysis and has a more significant effect on T1 values than COL. Considering that COL and GAG are the most abundant biomacromolecules in the cartilage, this study is particularly useful for the real-time MRI-guided assessment of cartilage regeneration. A clinical case is reported as an in vivo demonstration, which is consistent with our in vitro results. The established quantitative relation plays a critical academic role in establishing an international standard ISO/TS24560-1:2022 'Clinical evaluation of regenerative knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping' drafted by us and approved by International Standard Organization.

Regiodivergent C-H Acylation of Arenes by Switching from Ionic- to Radical-Type Chemistry Using NHC Catalysis.

The Friedel-Crafts acylation reaction, which belongs to the class of electrophilic aromatic substitutions is a highly valuable and versatile reaction in synthesis. Regioselectivity is predictable and determined by electronic as well as steric factors of the (hetero)arene substrate. Herein, a radical approach for the acylation of arenes and heteroarenes is presented. C-H acylation is achieved through mild cooperative photoredox/NHC radical catalysis with the cross-coupling of an arene radical cation with an NHC-bound ketyl radical as a key step. As compared to the classical Friedel-Crafts acylation, a regiodivergent outcome is observed upon switching from the ionic to the radical mode. In these divergent reactions, aroyl fluorides act as the acylation reagents in both the ionic as well as the radical process.

Genome-Wide Identification, Characterization, and Expression Analysis of SPIRAL1 Family Genes in Legume Species.

The SPIRAL1 (SPR1) gene family encodes microtubule-associated proteins that are essential for the anisotropic growth of plant cells and abiotic stress resistance. Currently, little is known about the characteristics and roles of the gene family outside of Arabidopsis thaliana. This study intended to investigate the SPR1 gene family in legumes. In contrast to that of A. thaliana, the gene family has undergone shrinking in the model legume species Medicago truncatula and Glycine max. While the orthologues of SPR1 were lost, very few SPR1-Like (SP1L) genes were identified given the genome size of the two species. Specifically, the M. truncatula and G. max genomes only harbor two MtSP1L and eight GmSP1L genes, respectively. Multiple sequence alignment showed that all these members contain conserved N- and C-terminal regions. Phylogenetic analysis clustered the legume SP1L proteins into three clades. The SP1L genes showed similar exon-intron organizations and similar architectures in their conserved motifs. Many essential cis-elements are present in the promoter regions of the MtSP1L and GmSP1L genes associated with growth and development, plant hormones, light, and stress. The expression analysis revealed that clade 1 and clade 2 SP1L genes have relatively high expression in all tested tissues in Medicago and soybean, suggesting their function in plant growth and development. MtSP1L-2, as well as clade 1 and clade 2 GmSP1L genes, display a light-dependent expression pattern. The SP1L genes in clade 2 (MtSP1L-2, GmSP1L-3, and GmSP1L-4) were significantly induced by sodium chloride treatment, suggesting a potential role in the salt-stress response. Our research provides essential information for the functional studies of SP1L genes in legume species in the future.

A Facile Composite Strategy to Prepare a Biodegradable Polymer Based Radiopaque Raw Material for "Visualizable" Biomedical Implants.

Enabling a biodegradable polymer radiopaque under X-ray is much desired for many medical devices. Physical blending of a present biodegradable polymer and a commercialized medical contrast agent is convenient yet lacks comprehensive fundamental research. Herein, we prepared a biodegradable polymer-based radiopaque raw material by blending poly(l-lactic acid) (PLLA or simply PLA) and iohexol (IHX), where PLA constituted the continuous phase and IHX particles served as the dispersed phase. The strong X-ray adsorption of IHX enabled the composite radiopaque; the hydrolysis of the polyester and the water solubility of the contrast agent enabled the composite biodegradable in an aqueous medium. The idea was confirmed by in vitro characterizations of the resultant composite, in vivo subcutaneous implantation in rats up to 6 months, and the clear visualization of a part of a biodegradable occluder in a Bama piglet under X-ray. We also found that the crystallization of PLA was significantly enhanced in the presence of the solid particles, which should be taken into consideration in the design of an appropriate biomaterial composite because crystallization degree influences the biodegradation rate and mechanical property of a material to a large extent. We further tried to introduce a small amount of poly(vinylpyrrolidone) into the blend of PLA and IHX. Compared to the bicomponent composite, the tricomponent one exhibited decreased modulus and increased elongation at break and tensile strength. This paves more ways for researchers to select appropriate raw materials according to the regenerated tissue and the application site.

3D-Printed Porous Scaffolds of Hydrogels Modified with TGF-ß1 Binding Peptides to Promote In Vivo Cartilage Regeneration and Animal Gait Restoration.

The treatment of cartilage injury and osteoarthritis has been a classic problem for many years. The idea of in situ tissue regeneration paves a way for osteochondral repair in vivo. Herein, a hydrogel scaffold linked with bioactive peptides that can selectively adsorb transforming growth factor ß1 (TGF-ß1) was hypothesized to not only afford cell ingrowth space but also induce the endogenous TGF-ß1 recruitment for chondrogenesis promotion. In this study, bilayered porous scaffolds with gelatin methacryloyl (GelMA) hydrogels as a matrix were constructed via three-dimensional (3D) printing, of which the upper layer was covalently bound with bioactive peptides that can adsorb TGF-ß1 for cartilage repair and the lower layer was blended with hydroxyapatite for subchondral regeneration. The scaffolds showed promising therapeutic efficacy proved by cartilage and osteogenic induction in vitro and osteochondral repair of rats in vivo. In particular, the animal gait behavior was recovered after the in situ tissue regeneration, and the corresponding gait analysis demonstrated the promotion of tissue regeneration induced by the porous hydrogels with the binding peptides.

'Invisible' orthodontics by polymeric 'clear' aligners molded on 3D-printed personalized dental models.

The malalignment of teeth is treated classically by metal braces with alloy wires, which has an unfavorable influence on the patients appearance during the treatment. With the development of digitization, computer simulation and three-dimensional (3D) printing technology, herein, a modern treatment was tried using clear polymeric aligners, which were fabricated by molding polyurethane films via thermoforming on the 3D-printed personalized dental models. The key parameters of photocurable 3D printing of dental models and the mechanical properties of the clear aligner film material were examined. The precision of a 3D-printed dental model mainly relied on characteristics of photocurable resin, the resolution of light source and the exposure condition, which determined the eventual shape of the molded clear aligner and thus the orthodontic treatment efficacy. The biocompatibility of the polyurethane film material was confirmed through cytotoxicity and hemolysis tests in vitro. Following a series of 3D-printed personalized dental models and finite element analysis to predict and plan the fabrication and orthodontic processes, corresponding clear aligners were fabricated and applied in animal experiments, which proved the efficacy and biocompatibility in vivo. Clinical treatments of 120 orthodontic cases were finally carried out with success, which highlights the advantage of the clear aligners as an esthetic, compatible and efficient appliance.

Borole/Borapyramidane Relationship.

Boroles and borapyramidanes are classical and nonclassical constitutional isomers, respectively. It is here shown that they can indeed be interconverted. Treatment of the bis(alkynyl)B(C6F5) SMe2 adduct 3·SMe2 with HB(C6F5)2 gave borole 1·SMe2, featuring trimethylsilyl substituents in both α positions to boron, by means of a 1,1-hydroboration/alkenylboration sequence. Photolysis of the classical borole adduct 1·SMe2 resulted in rearrangement to its nonclassical structural isomer, borapyramidane 2, in high yield, which exhibits a vicinal pair of trimethylsilyl substituents at the square pyramidane base. Neutral borapyramidane 2 is a rare example of an isoster of the (CH)5+ pyramidane cation. Thermolysis of borapyramidane 2 in the presence of SMe2 at 60 °C re-formed borole 1·SMe2, which converted at 100 °C to 2,3-bis-silyl-substituted borole isomer 8·SMe2. Its photolysis also gave borapyramidane 2. Prolonged photolysis of 2 at elevated temperatures converted this to borapyramidane isomer 10 containing a pair of trimethylsilyl groups in 1,3-position at its square C4-pyramidal base. The borole and borapyramidane isomers were characterized by X-ray diffraction, and the system was analyzed by density functional theory (DFT) calculations.

Aroyl Fluorides as Bifunctional Reagents for Dearomatizing Fluoroaroylation of Benzofurans.

The 2,3-dihydrobenzofuran scaffold is widely found in natural products and biologically active compounds. Herein, dearomatizing 2,3-fluoroaroylation of benzofurans with aroyl fluorides as bifunctional reagents to access 2,3-difunctionalized dihydrobenzofurans is reported. The reaction that occurs by cooperative NHC/photoredox catalysis provides 3-aroyl-2-fluoro-2,3-dihydrobenzofurans with moderate to good yield and high diastereoselectivity. Cascades proceed via radical/radical cross-coupling of a benzofuran radical cation generated in the photoredox catalysis cycle with a neutral ketyl radical formed through the NHC catalysis cycle. The redox-neutral transformation exhibits broad substrate scope and high functional group compatibility. With anhydrides as bifunctional reagents, dearomatizing aroyloxyacylation of benzofurans is achieved and the strategy can also be applied to N-acylated indoles to afford 3-aroyl-2-fluoro-dihydroindoles.

Magnetic resonance imaging for non-invasive clinical evaluation of normal and regenerated cartilage.

With the development of tissue engineering and regenerative medicine, it is much desired to establish bioimaging techniques to monitor the real-time regeneration efficacy in vivo in a non-invasive way. Herein, we tried magnetic resonance imaging (MRI) to evaluate knee cartilage regeneration after implanting a biomaterial scaffold seeded with chondrocytes, namely, matrix-induced autologous chondrocyte implantation (MACI). After summary of the T2 mapping and the T1-related delayed gadolinium-enhanced MRI imaging of cartilage (dGEMRIC) in vitro and in vivo in the literature, these two MRI techniques were tried clinically. In this study, 18 patients were followed up for 1 year. It was found that there was a significant difference between the regeneration site and the neighboring normal site (control), and the difference gradually diminished with regeneration time up to 1 year according to both the quantitative T1 and T2 MRI methods. We further established the correlation between the quantitative evaluation of MRI and the clinical Lysholm scores for the first time. Hence, the MRI technique was confirmed to be a feasible semi-quantitative yet non-invasive way to evaluate the in vivo regeneration of knee articular cartilage.

Direct Access to α-Aminosilanes Enabled by Visible-Light-Mediated Multicomponent Radical Cross-Coupling.

α-Aminosilanes are an important class of organic compounds that show biological activity. In this communication, a new approach to α-aminosilanes that utilizes photoredox catalysis to enable three-component coupling of organo(tristrimethylsilyl)silanes with feedstock alkylamines and aldehydes is presented. A wide range of highly functionalized α-aminosilanes can be obtained in good yields under mild conditions. Both primary amines and secondary amines are compatible with this transformation. Moreover, optically pure α-aminosilanes are accessible by using chiral amines. Mechanistic studies indicate that reactions proceed through radical/radical cross-coupling of silyl radicals with α-amino alkyl radicals.

Three-Component Aminoarylation of Electron-Rich Alkenes by Merging Photoredox with Nickel Catalysis.

A three-component 1,2-aminoarylation of vinyl ethers, enamides, ene-carbamates and vinyl thioethers by synergistic photoredox and nickel catalysis is reported. 2,2,2-Trifluoroethoxy carbonyl protected α-amino-oxy acids are used as amidyl radical precursors. anti-Markovnikov addition of the amidyl radical to the alkene and Ni-mediated radical/transition metal cross over lead to the corresponding 1,2-aminoarylation product. The radical cascade, which can be conducted under practical and mild conditions, features high functional group tolerance and broad substrate scope. Stereoselective 1,2-aminoarylation is achieved using a L-(+)-lactic acid derived vinyl ether as the substrate, offering a novel route for the preparation of protected enantiopure α-arylated ß-amino alcohols. In addition, 1,2-aminoacylation of vinyl ethers is achieved by using an acyl succinimide as the electrophile for the Ni-mediated radical coupling.

Visible Light-Driven Radical-Mediated C-C Bond Cleavage/Functionalization in Organic Synthesis.

Thermal C-C bond cleavage reactions allow the construction of structurally diverse molecular skeletons via predictable and efficient bond reorganizations. Visible light photoredox-catalyzed radical-mediated C-C bond cleavage reactions have recently emerged as a powerful alternative method for overcoming the thermodynamic and kinetic barrier of C-C bond cleavage in diverse molecular scaffolds. In recent years, a plethora of elegant and useful reactions have been invented, and the products are sometimes otherwise inaccessible by classic thermal reactions. Considering the great influence and synthetic potential of these reactions, we provide a summary of the state of art visible light-driven radical-mediated C-C bond cleavage/functionalization strategies with a specific emphasis on the working models. We hoped that this review will be useful for medicinal and synthetic organic chemists and will inspire further reaction development in this interesting area.

Cell-Free Bilayered Porous Scaffolds for Osteochondral Regeneration Fabricated by Continuous 3D-Printing Using Nascent Physical Hydrogel as Ink.

Cartilage is difficult to self-repair and it is more challenging to repair an osteochondral defects concerning both cartilage and subchondral bone. Herein, it is hypothesized that a bilayered porous scaffold composed of a biomimetic gelatin hydrogel may, despite no external seeding cells, induce osteochondral regeneration in vivo after being implanted into mammal joints. This idea is confirmed based on the successful continuous 3D-printing of the bilayered scaffolds combined with the sol-gel transition of the aqueous solution of a gelatin derivative (physical gelation) and photocrosslinking of the gelatin methacryloyl (gelMA) macromonomers (chemical gelation). At the direct printing step, a nascent physical hydrogel is extruded, taking advantage of non-Newtonian and thermoresponsive rheological properties of this 3D-printing ink. In particular, a series of crosslinked gelMA (GelMA) and GelMA-hydroxyapatite bilayered hydrogel scaffolds are fabricated to evaluate the influence of the spacing of 3D-printed filaments on osteochondral regeneration in a rabbit model. The moderately spaced scaffolds output excellent regeneration of cartilage with cartilaginous lacunae and formation of subchondral bone. Thus, tricky rheological behaviors of soft matter can be employed to improve 3D-printing, and the bilayered hybrid scaffold resulting from the continuous 3D-printing is promising as a biomaterial to regenerate articular cartilage.

Oligosilanes as Silyl Radical Precursors through Oxidative Si-Si Bond Cleavage Using Redox Catalysis.

Oligosilanes are of great interest in the fields of organic photonics and electronics. In this communication, a highly efficient visible-light-mediated hydrosilylation of electron-deficient alkenes through cleavage of a trimethylsilyl-polysilanyl Si-Si bond is explored. These reactions smoothly occur on readily available organo(tristrimethylsilyl)silanes and other oligosilanes in the presence of an IrIII -based photo-redox catalyst under visible light irradiation. Silyl radicals are generated through single electron oxidation of the oligosilane assisted by the solvent. The introduced method exhibits broad substrate scope and high functional group tolerance with respect to the organo(tristrimethylsilyl)silane and alkene components, enabling the construction of functionalized trisilanes. In addition, this catalytic system can be also applied to highly strained bicyclo[1.1.0]butanes as silyl radical acceptors.

When Light Meets Nitrogen-Centered Radicals: From Reagents to Catalysts.

Nitrogen-centered radicals (NCRs) are a versatile class of highly reactive species that have a longer history than the classical carbon-based radicals in synthetic chemistry. Depending on the N-hybridization and substitution patterns, NCRs can serve as electrophiles or nucleophiles to undergo various radical transformations. Despite their power, progress in nitrogen-radical chemistry is still slow compared with the popularity of carbon radicals, and their considerable synthetic potential has been largely underexplored, which is, as concluded by Zard, mainly hampered by "a dearth of convenient access to these species and a lack of awareness pertaining to their reactivity".Over the past decade, visible-light photoredox catalysis has been established as a powerful toolbox that synthetic chemists can use to generate a diverse range of radical intermediates from native organic functional groups via a single electron transfer process or energy transfer under mild reaction conditions. This catalytic strategy typically obviates the need for external stoichiometric activation reagents or toxic initiators and often enables traditionally inaccessible ionic chemical reactions. On the basis of our long-standing interest in nitrogen chemistry and catalysis, we have emphasized the use of visible-light photoredox catalysis as a tactic to discover and develop novel methods for generating NCRs in a controlled fashion and synthetic applications. In this Account, we describe our recent advances in the development of visible-light-driven photoredox-catalyzed generation of NCRs and their synthetic applications.Inspired by the natural biological proton-coupled electron transfer (PCET) process, we first developed a strategy of visible-light-driven photoredox-catalyzed oxidative deprotonation electron transfer to activate the N-H bonds of hydrazones, benzamides, and sulfonamides to give the corresponding NCRs under mild reaction conditions. With these reactive species, we then achieved a range of 5-exo and 6-endo radical cyclizations as well as cascade reactions in a highly regioselective manner, providing access to a variety of potentially useful nitrogen heterocycles. To further expand the repertoire of possible reactions of NCRs, we also revealed that iminyl radicals, derived from O-acyl cycloalkanone oxime esters, can undergo facile ring-opening C-C bond cleavage to give cyanoalkyl radicals. These newly formed radical species can further undergo a variety of C-C bond-forming reactions to allow the synthesis of diverse distally functionalized alkyl nitriles. Stimulated by these studies, we further developed a wide variety of visible-light-driven copper-catalyzed radical cross-coupling reactions of cyanoalkyl radicals. Because of their inherent highly reactive and transient properties, the strategy of heteroatom-centered radical catalysis is still largely underexplored in organic synthesis. Building on our understanding of the fundamental chemistry of NCRs, we also developed for the first time the concept of NCR covalent catalysis, which involves the use of in situ-photogenerated NCRs to activate allyl sulfones, vinylcyclopropanes, and N-tosyl vinylaziridines. This catalytic strategy has thus enabled efficient difunctionalization of various alkenes and late-stage modification of complex biologically active molecules.In this Account, we describe a panoramic picture of our recent contributions since 2014 to the development and application of the visible-light-driven photoredox systems in the field of NCR chemistry. These studies provide not only efficient methods for the synthesis of functionally rich molecules but also some insight into the exploration of new reactivity or reaction modes of NCRs.