67 results on '"Gaharwar, Akhilesh K."'
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2. Material assembly from collective action of shape-changing polymers
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Abdelrahman, Mustafa K., Wagner, Robert J., Kalairaj, Manivannan Sivaperuman, Zadan, Mason, Kim, Min Hee, Jang, Lindy K., Wang, Suitu, Javed, Mahjabeen, Dana, Asaf, Singh, Kanwar Abhay, Hargett, Sarah E., Gaharwar, Akhilesh K., Majidi, Carmel, Vernerey, Franck J., and Ware, Taylor H.
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Some animals form transient, responsive and solid-like ensembles through dynamic structural interactions. These ensembles demonstrate emergent responses such as spontaneous self-assembly, which are difficult to achieve in synthetic soft matter. Here we use shape-morphing units comprising responsive polymers to create solids that self-assemble, modulate their volume and disassemble on demand. The ensemble is composed of a responsive hydrogel, liquid crystal elastomer or semicrystalline polymer ribbons that reversibly bend or twist. The dispersions of these ribbons mechanically interlock, inducing reversible aggregation. The aggregated liquid crystal elastomer ribbons have a 12-fold increase in the yield stress compared with cooled dispersion and contract by 34% on heating. Ribbon type, concentration and shape dictate the aggregation and govern the global mechanical properties of the solid that forms. Coating liquid crystal elastomer ribbons with a liquid metal begets photoresponsive and electrically conductive aggregates, whereas seeding cells on hydrogel ribbons enables self-assembling three-dimensional scaffolds, providing a versatile platform for the design of dynamic materials.
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- 2024
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3. Nanobio Interface Between Proteins and 2D Nanomaterials.
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Roy, Shounak, Aastha, Deo, Kaivalya A., Dey, Kashmira, Gaharwar, Akhilesh K., and Jaiswal, Amit
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- 2023
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4. Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing.
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Keshavarz, Mozhgan, Alizadeh, Parvin, Kadumudi, Firoz Babu, Orive, Gorka, Gaharwar, Akhilesh K., Castilho, Miguel, Golafshan, Nasim, and Dolatshahi-Pirouz, Alireza
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- 2023
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5. Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing
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Keshavarz, Mozhgan, Alizadeh, Parvin, Kadumudi, Firoz Babu, Orive, Gorka, Gaharwar, Akhilesh K., Castilho, Miguel, Golafshan, Nasim, and Dolatshahi-Pirouz, Alireza
- Abstract
Several studies have shown that nanosilicate-reinforced scaffolds are suitable for bone regeneration. However, hydrogels are inherently too soft for load-bearing bone defects of critical sizes, and hard scaffolds typically do not provide a suitable three-dimensional (3D) microenvironment for cells to thrive, grow, and differentiate naturally. In this study, we bypass these long-standing challenges by fabricating a cell-free multi-level implant consisting of a porous and hard bone-like framework capable of providing load-bearing support and a softer native-like phase that has been reinforced with nanosilicates. The system was tested with rat bone marrow mesenchymal stem cells in vitro and as a cell-free system in a critical-sized rat bone defect. Overall, our combinatorial and multi-level implant design displayed remarkable osteoconductivity in vitro without differentiation factors, expressing significant levels of osteogenic markers compared to unmodified groups. Moreover, after 8 weeks of implantation, histological and immunohistochemical assays indicated that the cell-free scaffolds enhanced bone repair up to approximately 84% following a near-complete defect healing. Overall, our results suggest that the proposed nanosilicate bioceramic implant could herald a new age in the field of orthopedics.
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- 2023
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6. Nanoengineered Ink for Designing 3D Printable Flexible Bioelectronics.
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Deo, Kaivalya A., Jaiswal, Manish K., Abasi, Sara, Lokhande, Giriraj, Bhunia, Sukanya, Nguyen, Thuy-Uyen, Namkoong, Myeong, Darvesh, Kamran, Guiseppi-Elie, Anthony, Tian, Limei, and Gaharwar, Akhilesh K.
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- 2022
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7. Intra‐Articular Injectable Biomaterials for Cartilage Repair and Regeneration
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Kalairaj, Manivannan Sivaperuman, Pradhan, Ridhi, Saleem, Waqas, Smith, Morgan M., and Gaharwar, Akhilesh K.
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Osteoarthritis is a degenerative joint disease characterized by cartilage deterioration and subsequent inflammatory changes in the underlying bone. Injectable hydrogels have emerged as a promising approach for controlled drug delivery in cartilage therapies. This review focuses on the latest developments in utilizing injectable hydrogels as vehicles for targeted drug delivery to promote cartilage repair and regeneration. The pathogenesis of osteoarthritis is discussed to provide a comprehensive understanding of the disease progression. Subsequently, the various types of injectable hydrogels used for intra‐articular delivery are discussed. Specifically, physically and chemically crosslinked injectable hydrogels are critically analyzed, with an emphasis on their fabrication strategies and their capacity to encapsulate and release therapeutic agents in a controlled manner. Furthermore, the potential of incorporating growth factors, anti‐inflammatory drugs, and cells within these injectable hydrogels are discussed. Overall, this review offers a comprehensive guide to navigating the landscape of hydrogel‐based therapeutics in osteoarthritis. Injectable biomaterials have emerged as a prominent approach for therapeutic delivery in cartilage repair and regeneration. This review offers brief insights into the pathogenesis of osteoarthritis and critically evaluates recent advancements in injectable biomaterials for these applications. Furthermore, it also discusses fabrication strategies for the encapsulation and release of therapeutics, including growth factors, anti‐inflammatory drugs, and stem cells.
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- 2024
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8. Coiled Coil Crosslinked Alginate Hydrogels Dampen Macrophage-Driven Inflammation.
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Clapacs, Zain, ONeill, Conor L., Shrimali, Paresh, Lokhande, Giriraj, Files, Megan, Kim, Darren D., Gaharwar, Akhilesh K., and Rudra, Jai S.
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- 2022
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9. Nanoengineered Ink for Designing 3D Printable Flexible Bioelectronics
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Deo, Kaivalya A., Jaiswal, Manish K., Abasi, Sara, Lokhande, Giriraj, Bhunia, Sukanya, Nguyen, Thuy-Uyen, Namkoong, Myeong, Darvesh, Kamran, Guiseppi-Elie, Anthony, Tian, Limei, and Gaharwar, Akhilesh K.
- Abstract
Flexible electronics require elastomeric and conductive biointerfaces with native tissue-like mechanical properties. The conventional approaches to engineer such a biointerface often utilize conductive nanomaterials in combination with polymeric hydrogels that are cross-linked using toxic photoinitiators. Moreover, these systems frequently demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. To address these challenges, we developed a class of shear-thinning hydrogels as biomaterial inks for 3D printing flexible bioelectronics. These hydrogels are engineered through a facile vacancy-driven gelation of MoS2nanoassemblies with naturally derived polymer-thiolated gelatin. Due to shear-thinning properties, these nanoengineered hydrogels can be printed into complex shapes that can respond to mechanical deformation. The chemically cross-linked nanoengineered hydrogels demonstrate a 20-fold rise in compressive moduli and can withstand up to 80% strain without permanent deformation, meeting human anatomical flexibility. The nanoengineered network exhibits high conductivity, compressive modulus, pseudocapacitance, and biocompatibility. The 3D-printed cross-linked structure demonstrates excellent strain sensitivity and can be used as wearable electronics to detect various motion dynamics. Overall, the results suggest that these nanoengineered hydrogels offer improved mechanical, electronic, and biological characteristics for various emerging biomedical applications including 3D-printed flexible biosensors, actuators, optoelectronics, and therapeutic delivery devices.
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- 2022
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10. Coiled Coil Crosslinked Alginate Hydrogels Dampen Macrophage-Driven Inflammation
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Clapacs, Zoe, ONeill, Conor L., Shrimali, Paresh, Lokhande, Giriraj, Files, Megan, Kim, Darren D., Gaharwar, Akhilesh K., and Rudra, Jai S.
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Alginate hydrogels are widely used for tissue engineering and regenerative medicine due to their excellent biocompatibility. A facile and commonly used strategy to crosslink alginate is the addition of Ca2+that leads to hydrogelation. However, extracellular Ca2+is a secondary messenger in activating inflammasome pathways following physical injury or pathogenic insult, which carries the risk of persistent inflammation and scaffold rejection. Here, we present graft copolymers of charge complementary heterodimeric coiled coil (CC) peptides and alginate that undergo supramolecular self-assembly to form Ca2+free alginate hydrogels. The formation of heterodimeric CCs was confirmed using circular dichroism spectroscopy, and scanning electron microscopy revealed a significant difference in crosslink density and homogeneity between Ca2+and CC crosslinked gels. The resulting hydrogels were self-supporting and display shear-thinning and shear-recovery properties. In response to lipopolysaccharide (LPS) stimulation, peritoneal macrophages and bone marrow-derived dendritic cells cultured in the CC crosslinked gels exhibited a 10-fold reduction in secretion of the proinflammatory cytokine IL-1β compared to Ca2+crosslinked gels. A similar response was also observed in vivo upon peritoneal delivery of Ca2+or CC crosslinked gels. Analysis of peritoneal lavage showed that macrophages in mice injected with Ca2+crosslinked gels display a more inflammatory phenotype compared to macrophages from mice injected with CC crosslinked gels. These results suggest that CC peptides by virtue of their tunable sequence–structure–function relationship and mild gelation conditions are promising alternative crosslinkers for alginate and other biopolymer scaffolds used in tissue engineering.
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- 2022
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11. Development of Nanosilicate–Hydrogel Composites for Sustained Delivery of Charged Biopharmaceutics.
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Stealey, Samuel T., Gaharwar, Akhilesh K., Pozzi, Nicola, and Zustiak, Silviya Petrova
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- 2021
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12. Polymer-Coated Extracellular Vesicles for Selective Codelivery of Chemotherapeutics and siRNA to Cancer Cells.
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Jhan, Yong-Yu, Palou Zuniga, Guillermo, Singh, Kanwar Abhay, Gaharwar, Akhilesh K., Alge, Daniel L., and Bishop, Corey J.
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- 2021
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13. Self-Assembly of Block Heterochiral Peptides into Helical Tapes.
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Clover, Tara M., O'Neill, Conor L., Appavu, Rajagopal, Lokhande, Giriraj, Gaharwar, Akhilesh K., Posey, Ammon E., White, Mark A., and Rudra, Jai S.
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- 2020
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14. Development of Nanosilicate–Hydrogel Composites for Sustained Delivery of Charged Biopharmaceutics
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Stealey, Samuel T., Gaharwar, Akhilesh K., Pozzi, Nicola, and Zustiak, Silviya Petrova
- Abstract
Nanocomposite hydrogels containing two-dimensional nanosilicates (NS) have emerged as a new technology for the prolonged delivery of biopharmaceuticals. However, little is known about the physical–chemical properties governing the interaction between NS and proteins and the release profiles of NS–protein complexes in comparison to traditional poly(ethylene glycol) (PEG) hydrogel technologies. To fill this gap in knowledge, we fabricated a nanocomposite hydrogel composed of PEG and laponite and identified simple but effective experimental conditions to obtain sustained protein release, up to 23 times slower as compared to traditional PEG hydrogels, as determined by bulk release experiments and fluorescence correlation spectroscopy. Slowed protein release was attributed to the formation of NS–protein complexes, as NS–protein complex size was inversely correlated with protein diffusivity and release rates. While protein electrostatics, protein concentration, and incubation time were important variables to control protein–NS complex formation, we found that one of the most significant and less appreciated variable to obtain a sustained release of bioactive proteins was the buffer chosen for preparing the initial suspension of NS particles. The buffer was found to control the size of nanoparticles, the absorption potential, morphology, and stiffness of hydrogels. From these studies, we conclude that the PEG–laponite composite fabricated is a promising new platform for sustained delivery of positively charged protein therapeutics.
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- 2021
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15. Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue
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Chimene, David, Miller, Logan, Cross, Lauren M., Jaiswal, Manish K., Singh, Irtisha, and Gaharwar, Akhilesh K.
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Bioprinting is an emerging additive manufacturing approach to the fabrication of patient-specific, implantable three-dimensional (3D) constructs for regenerative medicine. However, developing cell-compatible bioinks with high printability, structural stability, biodegradability, and bioactive characteristics is still a primary challenge for translating 3D bioprinting technology to preclinical and clinal models. To overcome this challenge, we developed a nanoengineered ionic covalent entanglement (NICE) bioink formulation for 3D bone bioprinting. The NICE bioinks allow precise control over printability, mechanical properties, and degradation characteristics, enabling custom 3D fabrication of mechanically resilient, cellularized structures. We demonstrate cell-induced remodeling of 3D bioprinted scaffolds over 60 days, demonstrating deposition of nascent extracellular matrix proteins. Interestingly, the bioprinted constructs induce endochondral differentiation of encapsulated human mesenchymal stem cells (hMSCs) in the absence of osteoinducing agent. Using next-generation transcriptome sequencing (RNA-seq) technology, we establish the role of nanosilicates, a bioactive component of NICE bioink, to stimulate endochondral differentiation at the transcriptome level. Overall, the osteoinductive bioink has the ability to induce formation of osteo-related mineralized extracellular matrix by encapsulated hMSCs in growth factor-free conditions. Furthermore, we demonstrate the ability of NICE bioink to fabricate patient-specific, implantable 3D scaffolds for repair of craniomaxillofacial bone defects. We envision development of this NICE bioink technology toward a realistic clinical process for 3D bioprinting patient-specific bone tissue for regenerative medicine.
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- 2024
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16. Oxygen-Generating Photo-Cross-Linkable Hydrogels Support Cardiac Progenitor Cell Survival by Reducing Hypoxia-Induced Necrosis
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Alemdar, Neslihan, Leijten, Jeroen, Camci-Unal, Gulden, Hjortnaes, Jesper, Ribas, Joao, Paul, Arghya, Mostafalu, Pooria, Gaharwar, Akhilesh K., Qiu, Yiling, Sonkusale, Sameer, Liao, Ronglih, and Khademhosseini, Ali
- Abstract
Oxygen is essential to cell survival and tissue function. Not surprisingly, ischemia resulting from myocardial infarction induces cell death and tissue necrosis. Attempts to regenerate myocardial tissue with cell based therapies exacerbate the hypoxic stress by further increasing the metabolic burden. In consequence, implanted tissue engineered cardiac tissues suffer from hypoxia-induced cell death. Here, we report on the generation of oxygen-generating hydrogels composed of calcium peroxide (CPO) laden gelatin methacryloyl (GelMA). CPO-GelMA hydrogels released significant amounts of oxygen for over a period of 5 days under hypoxic conditions (1% O2). The released oxygen proved sufficient to relieve the metabolic stress of cardiac side population cells that were encapsulated within CPO-GelMA hydrogels. In particular, incorporation of CPO in GelMA hydrogels strongly enhanced cell viability as compared to GelMA-only hydrogels. Importantly, CPO-based oxygen generation reduced cell death by limiting hypoxia-induced necrosis. The current study demonstrates that CPO based oxygen-generating hydrogels could be used to transiently provide oxygen to cardiac cells under ischemic conditions. Therefore, oxygen generating materials such as CPO-GelMA can improve cell-based therapies aimed at treatment or regeneration of infarcted myocardial tissue.
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- 2024
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17. High-Throughput 3D-Printed Model of the Feto-Maternal Interface for the Discovery and Development of Preterm Birth Therapies
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Cherukuri, Rahul, Kammala, Ananth Kumar, Thomas, Tilu Jain, Saylor, Leah, Richardson, Lauren, Kim, Sungjin, Ferrer, Marc, Acedo, Cristina, Song, Min Jae, Gaharwar, Akhilesh K., Menon, Ramkumar, and Han, Arum
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Spontaneous preterm birth (PTB) affects around 11% of births, posing significant risks to neonatal health due to the inflammation at the fetal–maternal interface (FMi). This inflammation disrupts immune tolerance during pregnancy, often leading to PTB. While organ-on-a-chip (OOC) devices effectively mimic the physiology, pathophysiology, and responses of FMi, their relatively low throughput limits their utility in high-throughput testing applications. To overcome this, we developed a three-dimensional (3D)-printed model that fits in a well of a 96-well plate and can be mass-produced while also accurately replicating FMi, enabling efficient screening of drugs targeting FMi inflammation. Our model features two cell culture chambers (maternal and fetal cells) interlinked via an array of microfluidic channels. It was thoroughly validated, ensuring cell viability, metabolic activity, and cell-specific markers. The maternal chamber was exposed to lipopolysaccharides (LPS) to induce an inflammatory state, and proinflammatory cytokines in the culture supernatant were quantified. Furthermore, the efficacy of anti-inflammatory inhibitors in mitigating LPS-induced inflammation was investigated. Results demonstrated that our model supports robust cell growth, maintains viability, and accurately mimics PTB-associated inflammation. This high-throughput 3D-printed model offers a versatile platform for drug screening, promising advancements in drug discovery and PTB prevention.
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- 2024
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18. Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue.
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Chimene, David, Miller, Logan, Cross, Lauren M., Jaiswal, Manish K., Singh, Irtisha, and Gaharwar, Akhilesh K.
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- 2020
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19. Inorganic Biomaterials for Regenerative Medicine.
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Brokesh, Anna M. and Gaharwar, Akhilesh K.
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- 2020
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20. Self-Assembly of Block Heterochiral Peptides into Helical Tapes
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Clover, Tara M., O’Neill, Conor L., Appavu, Rajagopal, Lokhande, Giriraj, Gaharwar, Akhilesh K., Posey, Ammon E., White, Mark A., and Rudra, Jai S.
- Abstract
Patterned substitution of d-amino acids into the primary sequences of self-assembling peptides influences molecular-level packing and supramolecular morphology. We report that block heterochiral analogs of the model amphipathic peptide KFE8 (Ac-FKFEFKFE-NH2), composed of two FKFE repeat motifs with opposite chirality, assemble into helical tapes with dimensions greatly exceeding those of their fibrillar homochiral counterparts. At sufficient concentrations, these tapes form hydrogels with reduced storage moduli but retain the shear-thinning behavior and consistent mechanical recovery of the homochiral analogs. Varying the identity of charged residues (FRFEFRFE and FRFDFRFD) produced similarly sized nonhelical tapes, while a peptide with nonenantiomeric l- and d-blocks (FKFEFRFD) formed helical tapes closely resembling those of the heterochiral KFE8 analogs. A proposed energy-minimized model suggests that a kink at the interface between l- and d-blocks leads to the assembly of flat monolayers with nonidentical surfaces that display alternating stacks of hydrophobic and charged groups.
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- 2020
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21. Bioprinting 101: Design, Fabrication, and Evaluation of Cell-Laden 3D Bioprinted Scaffolds
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Deo, Kaivalya A., Singh, Kanwar Abhay, Peak, Charles W., Alge, Daniel L., and Gaharwar, Akhilesh K.
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3D bioprinting is an additive manufacturing technique that recapitulates the native architecture of tissues. This is accomplished through the precise deposition of cell-containing bioinks. The spatiotemporal control over bioink deposition permits for improved communication between cells and the extracellular matrix, facilitates fabrication of anatomically and physiologically relevant structures. The physiochemical properties of bioinks, before and after crosslinking, are crucial for bioprinting complex tissue structures. Specifically, the rheological properties of bioinks determines printability, structural fidelity, and cell viability during the printing process, whereas postcrosslinking of bioinks are critical for their mechanical integrity, physiological stability, cell survival, and cell functions. In this review, we critically evaluate bioink design criteria, specifically for extrusion-based 3D bioprinting techniques, to fabricate complex constructs. The effects of various processing parameters on the biophysical and biochemical characteristics of bioinks are discussed. Furthermore, emerging trends and future directions in the area of bioinks and bioprinting are also highlighted.Graphical abstractColor images are available online.Impact statementExtrusion-based 3D bioprinting is an emerging additive manufacturing approach for fabricating cell-laden tissue engineered constructs. This review critically evaluates bioink design criteria to fabricate complex tissue constructs. Specifically, pre- and post-printing evaluation approaches are described, as well as new research directions in the field of bioink development and functional bioprinting are highlighted.
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- 2020
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22. Comparison of Photo Cross Linkable Gelatin Derivatives and Initiators for Three-Dimensional Extrusion Bioprinting
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Tigner, Thomas J., Rajput, Satyam, Gaharwar, Akhilesh K., and Alge, Daniel L.
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The objective of this study was to evaluate the utility of gelatin–norbornene (GelNB), which is cross-linkable via thiol–ene click chemistry, and the photoinitiator lithium phenyl-2,4,6 trimethylbenzoylphosphinate (LAP) for 3D bioprinting. These materials were compared to two widely used materials, gelatin-methacryloyl (GelMA) and 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone (I2959). Characterization of photocuring kinetics revealed that LAP markedly improved the kinetics compared to I2959, which improved stability and print fidelity. Additionally, GelNB exhibited improved photocuring kinetics, improved stability, and decreased filament spreading compared to GelMA. However, inks containing GelMA yielded at lower stress, were more easily extruded, and produced smoother filaments. NIH 3T3 fibroblasts exhibited high viability in printed constructs, regardless of the gelatin derivative or photoinitiator used. Overall, these results support the selection of LAP over I2959 and suggest that GelNB could be a useful alternative to GelMA, although further work is needed to optimize GelNB extrusion.
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- 2020
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23. Inorganic Biomaterials for Regenerative Medicine
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Brokesh, Anna M. and Gaharwar, Akhilesh K.
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Regenerative medicine leverages the innate potential of the human body to efficiently repair and regenerate damaged tissues using engineered biomaterials. By designing responsive biomaterials with the appropriate biophysical and biochemical characteristics, cellular response can be modulated to direct tissue healing. Recently, inorganic biomaterials have been shown to regulate cellular responses including cell–cell and cell–matrix interactions. Moreover, ions released from these mineral-based biomaterials play a vital role in defining cell identity, as well as driving tissue-specific functions. The intrinsic properties of inorganic biomaterials, such as the release of bioactive ions (e.g., Ca, Mg, Sr, Si, B, Fe, Cu, Zn, Cr, Co, Mo, Mn, Au, Ag, V, Eu, and La), can be leveraged to induce phenotypic changes in cells or modulate the immune microenvironment to direct tissue healing and regeneration. Biophysical characteristics of biomaterials, such as topography, charge, size, electrostatic interactions, and stiffness can be modulated by addition of inorganic micro- and nanoparticles to polymeric networks have also been shown to play an important role in their biological response. In this Review, we discuss the recent emergence of inorganic biomaterials to harness the innate regenerative potential of the body. Specifically, we will discuss various biophysical or biochemical effects of inorganic-based materials in directing cellular response for regenerative medicine applications.
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- 2020
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24. Pectin Methacrylate (PEMA) and Gelatin-Based Hydrogels for Cell Delivery: Converting Waste Materials into Biomaterials.
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Mehrali, Mehdi, Thakur, Ashish, Kadumudi, Firoz Babu, Pierchala, Malgorzata Karolina, Cordova, Julio Alvin Vacacela, Shahbazi, Mohammad-Ali, Mehrali, Mohammad, Pennisi, Cristian Pablo, Orive, Gorka, Gaharwar, Akhilesh K., and Dolatshahi-Pirouz, Alireza
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- 2019
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25. Sustained and Prolonged Delivery of Protein Therapeutics from Two-Dimensional Nanosilicates.
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Cross, Lauren M., Carrow, James K., Ding, Xicheng, Singh, Kanwar Abhay, and Gaharwar, Akhilesh K.
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- 2019
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26. Gradient nanocomposite hydrogels for interface tissue engineering.
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Cross, Lauren M., Shah, Kunal, Palani, Sowmiya, Peak, Charles W., and Gaharwar, Akhilesh K.
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NANOCOMPOSITE materials ,HYDROGELS ,TISSUE engineering ,CELL adhesion ,POLYMERS - Abstract
Abstract Two-dimensional (2D) nanomaterials are an emerging class of materials with unique physical and chemical properties due to their high surface area and disc-like shape. Recently, these 2D nanomaterials have been investigated for a range of biomedical applications including tissue engineering, therapeutic delivery and bioimaging, due to their ability to physically reinforce polymeric networks. Here, we present a facile fabrication of a gradient scaffold with two natural polymers (gelatin methacryloyl (GelMA) and methacrylated kappa carrageenan (MκCA)) reinforced with 2D nanosilicates to mimic the native tissue interface. The addition of nanosilicates results in shear-thinning characteristics of prepolymer solution and increases the mechanical stiffness of crosslinked gradient structure. A gradient in mechanical properties, microstructures and cell adhesion characteristics was obtained using a microengineered flow channel. The gradient structure can be used to understand cell-matrix interactions and to design gradient scaffolds for mimicking tissue interfaces. Graphical Abstract We present a facile fabrication of a gradient scaffold with two natural polymers (gelatin methacrylate (GelMA) and methacrylated kappa carrageenan (MκCA)) reinforced with 2D nanosilicates to mimic the native tissue interface. A gradient in mechanical properties, microstructures and cell adhesion characteristics was achieved. This simple approach could be applied to regeneration of tissue interfaces where a natural gradient in the structural, mechanical, and biological properties exists. Image 1 [ABSTRACT FROM AUTHOR]
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- 2018
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27. A synthetic tumour microenvironment
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Gaharwar, Akhilesh K. and Singh, Irtisha
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A bioengineered model incorporating a synthetic extracellular matrix recapitulates the lymphoid tumour microenvironment, making it a valuable tool for drug testing and designing personalized therapies.
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- 2023
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28. Nanoengineered injectable hydrogels for wound healing application.
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Lokhande, Giriraj, Carrow, James K., Thakur, Teena, Xavier, Janet R., Parani, Madasamy, Bayless, Kayla J., and Gaharwar, Akhilesh K.
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HYDROGELS in medicine ,WOUND healing ,HEMORRHAGIC shock treatment ,SURGICAL hemostasis ,REGENERATIVE medicine ,VASCULAR endothelial growth factors - Abstract
We report injectable nanoengineered hemostats for enhanced wound healing and tissue regeneration. The nanoengineered system consists of the natural polysaccharide, κ-carrageenan (κCA), loaded with synthetic two-dimensional (2D) nanosilicates. Nanoengineered hydrogels showed shear-thinning characteristics and can be injected for minimally invasive approaches. The injectable gels can be physically crosslinked in presence of monovalent ions to form mechanically strong hydrogels. By controlling the ratio between κCA and nanosilicates, compressive stiffness of crosslinked hydrogels can be modulated between 20 and 200 kPa. Despite high mechanical stiffness, nanocomposite hydrogels are highly porous with an interconnected network. The addition of nanosilicates to κCA increases protein adsorption on nanocomposite hydrogels that results in enhance cell adhesion and spreading, increase platelets binding and reduce blood clotting time. Moreover, due to presence of nanosilicates, a range of therapeutic biomacromolecules can be deliver in a sustain manner. The addition of nanosilicates significantly suppresses the release of entrap vascular endothelial growth factor (VEGF) and facilitate in vitro tissue regeneration and wound healing. Thus, this multifunctional nanocomposite hydrogel can be used as an injectable hemostat and an efficient vehicle for therapeutic delivery to facilitate tissue regeneration. Statement of Significance Hemorrhage is a leading cause of death in battlefield wounds, anastomosis hemorrhage and percutaneous intervention. Thus, there is a need for the development of novel bioactive materials to reduce the likelihood of hemorrhagic shock stemming from internal wounds. Here, we introduce an injectable hemostat from kappa-carrageenan and two-dimensional (2D) nanosilicates. Nanosilicates mechanically reinforce the hydrogels, provide enhanced physiological stability and accelerate the clotting time by two-fold. The sustained release of entrapped therapeutics due to presence of nanosilicates promotes enhanced wound healing. The multifunctional nanocomposite hydrogels could be used as an injectable hemostat for penetrating injury and percutaneous intervention during surgery. [ABSTRACT FROM AUTHOR]
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- 2018
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29. Nanoengineered Colloidal Inks for 3D Bioprinting.
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Peak, Charles W., Stein, Jean, Gold, Karli A., and Gaharwar, Akhilesh K.
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- 2018
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30. Pectin Methacrylate (PEMA) and Gelatin-Based Hydrogels for Cell Delivery: Converting Waste Materials into Biomaterials
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Mehrali, Mehdi, Thakur, Ashish, Kadumudi, Firoz Babu, Pierchala, Malgorzata Karolina, Cordova, Julio Alvin Vacacela, Shahbazi, Mohammad-Ali, Mehrali, Mohammad, Pennisi, Cristian Pablo, Orive, Gorka, Gaharwar, Akhilesh K., and Dolatshahi-Pirouz, Alireza
- Abstract
The emergence of nontoxic, eco-friendly, and biocompatible polymers derived from natural sources has added a new and exciting dimension to the development of low-cost and scalable biomaterials for tissue engineering applications. Here, we have developed a mechanically strong and durable hydrogel composed of an eco-friendly biopolymer that exists within the cell walls of fruits and plants. Its trade name is pectin, and it bears many similarities with natural polysaccharides in the native extracellular matrix. Specifically, we have employed a new pathway to transform pectin into a ultraviolet (UV)-cross-linkable pectin methacrylate (PEMA) polymer. To endow this hydrogel matrix with cell differentiation and cell spreading properties, we have also incorporated thiolated gelatin into the system. Notably, we were able to fine-tune the compressive modulus of this hydrogel in the range ∼0.5 to ∼24 kPa: advantageously, our results demonstrated that the hydrogels can support growth and viability for a wide range of three-dimensionally (3D) encapsulated cells that include muscle progenitor (C2C12), neural progenitor (PC12), and human mesenchymal stem cells (hMSCs). Our results also indicate that PEMA-gelatin-encapsulated hMSCs can facilitate the formation of bonelike apatite after 5 weeks in culture. Finally, we have demonstrated that PEMA-gelatin can yield micropatterned cell-laden 3D constructs through UV light-assisted lithography. The simplicity, scalability, processability, tunability, bioactivity, and low-cost features of this new hydrogel system highlight its potential as a stem cell carrier that is capable of bridging the gap between clinic and laboratory.
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- 2019
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31. 3D-printed bioactive scaffolds from nanosilicates and PEOT/PBT for bone tissue engineering.
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Carrow, James K, Di Luca, Andrea, Dolatshahi-Pirouz, Alireza, Moroni, Lorenzo, and Gaharwar, Akhilesh K
- Abstract
Additive manufacturing (AM) has shown promise in designing 3D scaffold for regenerative medicine. However, many synthetic biomaterials used for AM are bioinert. Here, we report synthesis of bioactive nanocomposites from a poly(ethylene oxide terephthalate) (PEOT)/poly(butylene terephthalate) (PBT) (PEOT/PBT) copolymer and 2D nanosilicates for fabricating 3D scaffolds for bone tissue engineering. PEOT/PBT have been shown to support calcification and bone bonding ability in vivo, while 2D nanosilicates induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) in absence of osteoinductive agents. The effect of nanosilicates addition to PEOT/PBT on structural, mechanical and biological properties is investigated. Specifically, the addition of nanosilicate to PEOT/PBT improves the stability of nanocomposites in physiological conditions, as nanosilicate suppressed the degradation rate of copolymer. However, no significant increase in the mechanical stiffness of scaffold due to the addition of nanosilicates is observed. The addition of nanosilicates to PEOT/PBT improves the bioactive properties of AM nanocomposites as demonstrated in vitro.hMSCs readily proliferated on the scaffolds containing nanosilicates and resulted in significant upregulation of osteo-related proteins and production of mineralized matrix. The synergistic ability of nanosilicates and PEOT/PBT can be utilized for designing bioactive scaffolds for bone tissue engineering.
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- 2019
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32. Sustained and Prolonged Delivery of Protein Therapeutics from Two-Dimensional Nanosilicates
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Cross, Lauren M., Carrow, James K., Ding, Xicheng, Singh, Kanwar Abhay, and Gaharwar, Akhilesh K.
- Abstract
We present a nanoengineered system for sustained and prolonged delivery of protein therapeutics, which has the potential to impact current orthopedic regeneration strategies. Specifically, we introduce two-dimensional nanosilicates with a high surface area and charged characteristics for delivery of active proteins for more than 30 days. The nanosilicates show high binding efficacy without altering the protein conformation and bioactivity. The released proteins are able to maintain high activity as demonstrated by enhanced differentiation of human mesenchymal stem cells at 10-fold lower concentration compared to the exogenous control. Utilizing the nanosilicates as a delivery vehicle could minimize the negative side effects observed because of the use of supraphysiological dosages of protein therapeutics for orthopedic regeneration strategies.
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- 2019
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33. Clickable PEG hydrogel microspheres as building blocks for 3D bioprintingElectronic supplementary information (ESI) available: Details of microgel formulations, experimental data of cell growth and adhesion on microgels, videos of microgel printing. See DOI: 10.1039/c8bm01286e
- Author
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Xin, Shangjing, Chimene, David, Garza, Jay E., Gaharwar, Akhilesh K., and Alge, Daniel L.
- Abstract
Three-dimensional (3D) bioprinting is important in the development of complex tissue structures for tissue engineering and regenerative medicine. However, the materials used for bioprinting, referred to as bioinks, must have a balance between a high viscosity for rapid solidification after extrusion and low shear force for cytocompatibility, which is difficult to achieve. Here, a novel bioink consisting of poly(ethylene glycol) (PEG) microgels prepared viaoff-stoichiometry thiol–ene click chemistry is introduced. Importantly, the microgel bioink is easily extruded, exhibits excellent stability after printing due to interparticle adhesion forces, and can be photochemically annealed with a second thiol–ene click reaction to confer long-term stability to printed constructs. The modularity of the bioink is also an advantage, as the PEG microgels have highly tunable physicochemical properties. The low force required for extrusion and cytocompatibility of the thiol–ene annealing reaction also permit cell incorporation during printing with high viability, and cells are able to spread and proliferate in the interstitial spaces between the microgels after the constructs have been annealed. Overall, these results indicate that our microgel bioink is a promising and versatile platform that could be leveraged for bioprinting and regenerative manufacturing.
- Published
- 2019
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34. Sequential Thiol-Ene and Tetrazine Click Reactions for the Polymerization and Functionalization of Hydrogel Microparticles.
- Author
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Jivan, Faraz, Yegappan, Ramanathan, Pearce, Hannah, Carrow, James K., McShane, Michael, Gaharwar, Akhilesh K., and Alge, Daniel L.
- Published
- 2016
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35. Combinatorial Screening of Nanoclay-Reinforced Hydrogels: A Glimpse of the “Holy Grail” in Orthopedic Stem Cell Therapy?
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Hasany, Masoud, Thakur, Ashish, Taebnia, Nayere, Kadumudi, Firoz Babu, Shahbazi, Mohammad-Ali, Pierchala, Malgorzata Karolina, Mohanty, Soumyaranjan, Orive, Gorka, Andresen, Thomas L., Foldager, Casper Bindzus, Yaghmaei, Soheila, Arpanaei, Ayyoob, Gaharwar, Akhilesh K., Mehrali, Mehdi, and Dolatshahi-Pirouz, Alireza
- Abstract
Despite the promise of hydrogel-based stem cell therapies in orthopedics, a significant need still exists for the development of injectable microenvironments capable of utilizing the regenerative potential of donor cells. Indeed, the quest for biomaterials that can direct stem cells into bone without the need of external factors has been the “Holy Grail” in orthopedic stem cell therapy for decades. To address this challenge, we have utilized a combinatorial approach to screen over 63 nanoengineered hydrogels made from alginate, hyaluronic acid, and two-dimensional nanoclays. Out of these combinations, we have identified a biomaterial that can promote osteogenesis in the absence of well-established differentiation factors such as bone morphogenetic protein 2 (BMP2) or dexamethasone. Notably, in our “hit” formulations we observed a 36-fold increase in alkaline phosphate (ALP) activity and a 11-fold increase in the formation of mineralized matrix, compared to the control hydrogel. This induced osteogenesis was further supported by X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive X-ray spectroscopy. Additionally, the Montmorillonite-reinforced hydrogels exhibited high osteointegration as evident from the relatively stronger adhesion to the bone explants as compared to the control. Overall, our results demonstrate the capability of combinatorial and nanoengineered biomaterials to induce bone regeneration through osteoinduction of stem cells in a natural and differentiation-factor-free environment.
- Published
- 2018
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36. Rapid Osteogenic Enhancement of Stem Cells in Human Bone Marrow Using a Glycogen-Synthease-Kinase-3-Beta Inhibitor Improves Osteogenic Efficacy In Vitro and In Vivo
- Author
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Clough, Bret H., Zeitouni, Suzanne, Krause, Ulf, Chaput, Christopher D., Cross, Lauren M., Gaharwar, Akhilesh K., and Gregory, Carl A.
- Abstract
Non-union defects of bone are a major problem in orthopedics, especially for patients with a low healing capacity. Fixation devices and osteoconductive materials are used to provide a stable environment for osteogenesis and an osteogenic component such as autologous human bone marrow (hBM) is then used, but robust bone formation is contingent on the healing capacity of the patients. A safe and rapid procedure for improvement of the osteoanabolic properties of hBM is, therefore, sought after in the field of orthopedics, especially if it can be performed within the temporal limitations of the surgical procedure, with minimal manipulation, and at point-of-care. One way to achieve this goal is to stimulate canonical Wingless (cWnt) signaling in bone marrow-resident human mesenchymal stem cells (hMSCs), the presumptive precursors of osteoblasts in bone marrow. Herein, we report that the effects of cWnt stimulation can be achieved by transient (1–2 hours) exposure of osteoprogenitors to the GSK3ß-inhibitor (2'Z,3'E)-6-bromoindirubin-3'-oxime (BIO) at a concentration of 800 nM. Very-rapid-exposure-to-BIO (VRE-BIO) on either hMSCs or whole hBM resulted in the long-term establishment of an osteogenic phenotype associated with accelerated alkaline phosphatase activity and enhanced transcription of the master regulator of osteogenesis, Runx2. When VRE-BIO treated hBM was tested in a rat spinal fusion model, VRE-BIO caused the formation of a denser, stiffer, fusion mass as compared with vehicle treated hBM. Collectively, these data indicate that the VRE-BIO procedure may represent a rapid, safe, and point-of-care strategy for the osteogenic enhancement of autologous hBM for use in clinical orthopedic procedures. StemCellsTranslationalMedicine2018;7:342–353 Rapid and transient exposure of mesenchymal stem cells or whole bone marrow with a glycogen-synthease-3-beta inhibitor increases the osteogenic potential in vivo. Statistics calculated with Student's ttest (*, p?.05). Bar?=?0.75 mm.
- Published
- 2018
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37. Nanoengineered Ionic–Covalent Entanglement (NICE) Bioinks for 3D Bioprinting
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Chimene, David, Peak, Charles W., Gentry, James L., Carrow, James K., Cross, Lauren M., Mondragon, Eli, Cardoso, Guinea B., Kaunas, Roland, and Gaharwar, Akhilesh K.
- Abstract
We introduce an enhanced nanoengineered ionic-covalent entanglement (NICE) bioink for the fabrication of mechanically stiff and elastomeric 3D biostructures. NICE bioink formulations combine nanocomposite and ionic-covalent entanglement (ICE) strengthening mechanisms to print customizable cell-laden constructs for tissue engineering with high structural fidelity and mechanical stiffness. Nanocomposite and ICE strengthening mechanisms complement each other through synergistic interactions, improving mechanical strength, elasticity, toughness, and flow properties beyond the sum of the effects of either reinforcement technique alone. Herschel-Bulkley flow behavior shields encapsulated cells from excessive shear stresses during extrusion. The encapsulated cells readily proliferate and maintain high cell viability over 120 days within the 3D-printed structure, which is vital for long-term tissue regeneration. A unique aspect of the NICE bioink is its ability to print much taller structures, with higher aspect ratios, than can be achieved with conventional bioinks without requiring secondary supports. We envision that NICE bioinks can be used to bioprint complex, large-scale, cell-laden constructs for tissue engineering with high structural fidelity and mechanical stiffness for applications in custom bioprinted scaffolds and tissue engineered implants.
- Published
- 2018
- Full Text
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38. Effect of ionic strength on shear-thinning nanoclay–polymer composite hydrogelsElectronic supplementary information (ESI) available. See DOI: 10.1039/c8bm00469b
- Author
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SheikhiThese authors contributed equally to this work., Amir, Afewerki, Samson, Oklu, Rahmi, Gaharwar, Akhilesh K., and Khademhosseini, Ali
- Abstract
Nanoclay–polymer shear-thinning composites are designed for a broad range of biomedical applications, including tissue engineering, drug delivery, and additive biomanufacturing. Despite the advances in clay–polymer injectable nanocomposites, colloidal properties of layered silicates are not fully considered in evaluating the in vitroperformance of shear-thinning biomaterials (STBs). Here, as a model system, we investigate the effect of ions on the rheological properties and injectability of nanoclay–gelatin hydrogels to understand their behavior when prepared in physiological media. In particular, we study the effect of sodium chloride (NaCl) and calcium chloride (CaCl2), common salts in phosphate buffered saline (PBS) and cell culture media (e.g., Dulbecco's Modified Eagle's Medium, DMEM), on the structural organization of nanoclay (LAPONITE® XLG-XR, a hydrous lithium magnesium sodium silicate)-polymer composites, responsible for the shear-thinning properties and injectability of STBs. We show that the formation of nanoclay–polymer aggregates due to the ion-induced shrinkage of the diffuse double layer and eventually the liquid–solid phase separation decrease the resistance of STB against elastic deformation, decreasing the yield stress. Accordingly, the stress corresponding to the onset of structural breakdown (yield zone) is regulated by the ion type and concentration. These results are independent of the STB composition and can directly be translated into the physiological conditions. The exfoliated nanoclay undergoes visually undetectable aggregation upon mixing with gelatin in physiological media, resulting in heterogeneous hydrogels that phase separate under stress. This work provides fundamental insights into nanoclay–polymer interactions in physiological environments, paving the way for designing clay-based injectable biomaterials.
- Published
- 2018
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39. Shear-Thinning and Thermo-Reversible Nanoengineered Inks for 3D Bioprinting
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Wilson, Scott A., Cross, Lauren M., Peak, Charles W., and Gaharwar, Akhilesh K.
- Abstract
Three-dimensional (3D) printing is an emerging approach for rapid fabrication of complex tissue structures using cell-loaded bioinks. However, 3D bioprinting has hit a bottleneck in progress because of the lack of suitable bioinks that are printable, have high shape fidelity, and are mechanically resilient. In this study, we introduce a new family of nanoengineered bioinks consisting of kappa-carrageenan (κCA) and two-dimensional (2D) nanosilicates (nSi). κCA is a biocompatible, linear, sulfated polysaccharide derived from red algae and can undergo thermo-reversible and ionic gelation. The shear-thinning characteristics of κCA were tailored by nanosilicates to develop a printable bioink. By tuning κCA–nanosilicate ratios, the thermo-reversible gelation of the bioink can be controlled to obtain high printability and shape retention characteristics. The unique aspect of the nanoengineered κCA–nSi bioink is its ability to print physiologically-relevant-scale tissue constructs without requiring secondary supports. We envision that nanoengineered κCA–nanosilicate bioinks can be used to 3D print complex, large-scale, cell-laden tissue constructs with high structural fidelity and tunable mechanical stiffness for regenerative medicine.
- Published
- 2017
- Full Text
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40. Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces.
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Cross, Lauren M., Thakur, Ashish, Jalili, Nima A., Detamore, Michael, and Gaharwar, Akhilesh K.
- Subjects
BIOMATERIALS ,TISSUE engineering ,NANOSTRUCTURED materials ,NANOFABRICATION ,TISSUES - Abstract
Orthopedic interface tissue engineering aims to mimic the structure and function of soft-to-hard tissue junctions, particularly bone-ligament, bone-tendon, and bone-cartilage interfaces. A range of engineering approaches has been proposed to mimic the gradient architecture, physical properties and chemical characteristics of interface tissues using conventional polymeric biomaterials. Recent developments in nanomaterials and nanofabrication technologies introduce a range of synthesis and fabrication tools to effectively engineer the structure and function of native tissue interfaces. In this review, we will focus on nanoengineered strategies used to replicate the structural and functional aspects of native biological tissues for engineering bone-cartilage, bone-ligament, and bone-tendon interfaces. This review will also highlight some of the emerging applications and future potential of nanomaterials and fabrication technologies in engineering tissue interfaces. Statement of Significance A major challenge in engineering interfaces is to control the physical and structural characteristics of an artificial environment. The use of nanomaterials and nanoengineered strategies allow for greater control over the changes in structure and function at molecular and nanometer length scale. This review focuses on advanced nanomaterials and nanofabrication approaches developed to emulate bone-cartilage, bone-ligament, and bone-tendon interface regions. Some of the emerging nanoengineered biomaterials proposed to mimic tissue interfaces are also highlighted. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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41. Elastomeric and mechanically stiff nanocomposites from poly(glycerol sebacate) and bioactive nanosilicates.
- Author
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Kerativitayanan, Punyavee and Gaharwar, Akhilesh K.
- Subjects
ELASTOMERS ,NANOCOMPOSITE materials ,TISSUE engineering ,BONE regeneration ,BIOCOMPATIBILITY ,BIOACTIVE compounds - Abstract
Poly(glycerol sebacate) (PGS) has been proposed for tissue engineering applications owing to its tough elastomeric mechanical properties, biocompatibility and controllable degradation. However, PGS shows limited bioactivity and thus constraining its utilization for musculoskeletal tissue engineering. To address this issue, we developed bioactive, highly elastomeric, and mechanically stiff nanocomposites by covalently reinforcing PGS network with two-dimensional (2D) nanosilicates. Nanosilicates are ultrathin nanomaterials and can induce osteogenic differentiation of human stem cells in the absence of any osteogenic factors such as dexamethasone or bone morphogenetic proteins-2 (BMP2). The addition of nanosilicate to PGS matrix significantly enhances the mechanical stiffness without affecting the elastomeric properties. Moreover, nanocomposites with higher amount of nanosilicates have higher in vitro stability as determined by degradation kinetics. The increase in mechanical stiffness and in vitro stability is mainly attributed to enhanced interactions between nanosilicates and PGS. We evaluated the in vitro bioactivity of nanocomposite using preosteoblast cells. The addition of nanosilicates significantly enhances the cell adhesion, support cell proliferation, upregulate alkaline phosphates and mineralized matrix production. Overall, the combination of high mechanically stiffness and elastomericity, tailorable degradation profile, and the ability to promote osteogenic differentiation of PGS-nanosilicate can be used for regeneration of bone. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
42. Assessment of Local Heterogeneity in Mechanical Properties of Nanostructured Hydrogel Networks
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Meng, Zhaokai, Thakur, Teena, Chitrakar, Chandani, Jaiswal, Manish K., Gaharwar, Akhilesh K., and Yakovlev, Vladislav V.
- Abstract
Our current understanding of the mechanical properties of nanostructured biomaterials is rather limited to invasive/destructive and low-throughput techniques such as atomic force microscopy, optical tweezers, and shear rheology. In this report, we demonstrate the capabilities of recently developed dual Brillouin/Raman spectroscopy to interrogate the mechanical and chemical properties of nanostructured hydrogel networks. The results obtained from Brillouin spectroscopy show an excellent correlation with the conventional uniaxial and shear mechanical testing. Moreover, it is confirmed that, unlike the macroscopic conventional mechanical measurement techniques, Brillouin spectroscopy can provide the elasticity characteristic of biomaterials at a mesoscale length, which is remarkably important for understanding complex cell–biomaterial interactions. The proposed technique experimentally demonstrated the capability of studying biomaterials in their natural environment and may facilitate future fabrication and inspection of biomaterials for various biomedical and biotechnological applications.
- Published
- 2017
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43. Nanoengineered Osteoinductive and Elastomeric Scaffolds for Bone Tissue Engineering
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Kerativitayanan, Punyavee, Tatullo, Marco, Khariton, Margarita, Joshi, Pooja, Perniconi, Barbara, and Gaharwar, Akhilesh K.
- Abstract
Synthesis and fabrication of porous and elastomeric nanocomposite scaffolds from biodegradable poly(glycerol sebacate) (PGS) and osteoinductive nanosilicates is reported. Nanosilicates are mineral-based two-dimensional (2D) nanomaterials with high surface area which reinforced PGS network. The addition of nanosilicates to PGS resulted in mechanically stiff and elastomeric nanocomposites. The degradation rate and mechanical stiffness of nanocomposite network could be modulated by addition of nanosilicates. Nanocomposite scaffolds supported cell adhesion, spreading, and proliferation and promoted osteogenic differentiation of preosteoblasts. The addition of nanosilicates to PGS scaffolds increased alkaline phosphatase (ALP) activity and production of matrix mineralization. In vivo studies demonstrated biocompatibility and biodegradability of nanocomposite scaffolds. Overall, the combination of elasticity and tailorable stiffness, tunable degradation profiles, and the osteoinductive capability of the scaffolds offer a promising approach for bone tissue engineering.
- Published
- 2017
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44. Nanobio Interface Between Proteins and 2D Nanomaterials
- Author
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Roy, Shounak, Aastha, Deo, Kaivalya A., Dey, Kashmira, Gaharwar, Akhilesh K., and Jaiswal, Amit
- Abstract
Two-dimensional (2D) nanomaterials have significantly contributed to recent advances in material sciences and nanotechnology, owing to their layered structure. Despite their potential as multifunctional theranostic agents, the biomedical translation of these materials is limited due to a lack of knowledge and control over their interaction with complex biological systems. In a biological microenvironment, the high surface energy of nanomaterials leads to diverse interactions with biological moieties such as proteins, which play a crucial role in unique physiological processes. These interactions can alter the size, surface charge, shape, and interfacial composition of the nanomaterial, ultimately affecting its biological activity and identity. This review critically discusses the possible interactions between proteins and 2D nanomaterials, along with a wide spectrum of analytical techniques that can be used to study and characterize such interplay. A better understanding of these interactions would help circumvent potential risks and provide guidance toward the safer design of 2D nanomaterials as a platform technology for various biomedical applications.
- Published
- 2023
- Full Text
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45. Engineered Nanomaterials for Infection Control and Healing Acute and Chronic Wounds
- Author
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Parani, Madasamy, Lokhande, Giriraj, Singh, Ankur, and Gaharwar, Akhilesh K
- Abstract
Nanoengineered biomaterials have dramatically expanded the range of tools used for infection control and to accelerate wound healing. This review thoroughly describes the developments that are shaping this emerging field and evaluates the potential wound healing applications of recently developed engineered nanomaterials for both acute and chronic wounds. Specifically, we will assess the unique characteristics of engineered nanomaterials that render them applicable for wound healing and infection control. A range of engineered nanomaterials, including polymeric-, metallic- and ceramic-based nanomaterials, that could be used as therapeutic delivery agents to accelerate regeneration of damaged dermal and epidermal tissues are also detailed. Finally, we will detail the current state of engineered nanomaterials for wound regeneration and will identify promising new research directions in infection control.
- Published
- 2016
- Full Text
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46. Brillouin microspectroscopy of nanostructured biomaterials: photonics assisted tailoring mechanical properties
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Kabashin, Andrei V., Geohegan, David B., Dubowski, Jan J., Meng, Zhaokai, Jaiswal, Manish K., Chitrakar, Chandani, Thakur, Teena, Gaharwar, Akhilesh K., and Yakovlev, Vladislav V.
- Published
- 2016
- Full Text
- View/download PDF
47. Mechanically Stiff Nanocomposite Hydrogels at Ultralow Nanoparticle Content
- Author
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Jaiswal, Manish K., Xavier, Janet R., Carrow, James K., Desai, Prachi, Alge, Daniel, and Gaharwar, Akhilesh K.
- Abstract
Although hydrogels are able to mimic native tissue microenvironments, their utility for biomedical applications is severely hampered due to limited mechanical stiffness and low toughness. Despite recent progress in designing stiff and tough hydrogels, it is still challenging to achieve a cell-friendly, high modulus construct. Here, we report a highly efficient method to reinforce collagen-based hydrogels using extremely low concentrations of a nanoparticulate-reinforcing agent that acts as a cross-link epicenter. Extraordinarily, the addition of these nanoparticles at a 10 000-fold lower concentration relative to polymer resulted in a more than 10-fold increase in mechanical stiffness and a 20-fold increase in toughness. We attribute the high stiffness of the nanocomposite network to the chemical functionality of the nanoparticles, which enabled the cross-linking of multiple polymeric chains to the nanoparticle surface. The mechanical stiffness of the nanoengineered hydrogel can be tailored between 0.2 and 200 kPa simply by manipulating the size of the nanoparticles (4, 8, and 12 nm), as well as the concentrations of the nanoparticles and polymer. Moreover, cells can be easily encapsulated within the nanoparticulate-reinforced hydrogel network, showing high viability. In addition, encapsulated cells were able to sense and respond to matrix stiffness. Overall, these results demonstrate a facile approach to modulate the mechanical stiffness of collagen-based hydrogels and may have broad utility for various biomedical applications, including use as tissue-engineered scaffolds and cell/protein delivery vehicles.
- Published
- 2016
- Full Text
- View/download PDF
48. Bioactive Nanoengineered Hydrogels for Bone Tissue Engineering: A Growth-Factor-Free Approach
- Author
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Xavier, Janet R., Thakur, Teena, Desai, Prachi, Jaiswal, Manish K., Sears, Nick, Cosgriff-Hernandez, Elizabeth, Kaunas, Roland, and Gaharwar, Akhilesh K.
- Abstract
Despite bone’s impressive ability to heal after traumatic injuries and fractures, a significant need still exists for developing strategies to promote healing of nonunion defects. To address this issue, we developed collagen-based hydrogels containing two-dimensional nanosilicates. Nanosilicates are ultrathin nanomaterials with a high degree of anisotropy and functionality that results in enhanced surface interactions with biological entities compared to their respective three-dimensional counterparts. The addition of nanosilicates resulted in a 4-fold increase in compressive modulus along with an increase in pore size compared to collagen-based hydrogels. In vitroevaluation indicated that the nanocomposite hydrogels are capable of promoting osteogenesis in the absence of any osteoinductive factors. A 3-fold increase in alkaline phosphatase activity and a 4-fold increase in the formation of a mineralized matrix were observed with the addition of the nanosilicates to the collagen-based hydrogels. Overall, these results demonstrate the multiple functions of nanosilicates conducive to the regeneration of bone in nonunion defects, including increased network stiffness and porosity, injectability, and enhanced mineralized matrix formation in a growth-factor-free microenvironment.
- Published
- 2015
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49. Effect of biodegradation and de novo matrix synthesis on the mechanical properties of valvular interstitial cell-seeded polyglycerol sebacate–polycaprolactone scaffolds.
- Author
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Sant, Shilpa, Iyer, Dharini, Gaharwar, Akhilesh K., Patel, Alpesh, and Khademhosseini, Ali
- Subjects
BIODEGRADATION ,BIOMECHANICS ,POLYCAPROLACTONE ,TISSUE scaffolds ,HEART valve transplantation ,GLYCERIN ,EXTRACELLULAR matrix - Abstract
Abstract: The development of living heart valves that grow with the patient is a promising strategy for heart valve replacements in pediatric patients. Despite active research in the field of tissue engineered heart valves there have been limited efforts to optimize the balance between biodegradation of the scaffolds and de novo extracellular matrix (ECM) synthesis by cells and study their consequences on the mechanical properties of the cell-seeded construct. This study investigates the effect of in vitro degradation and ECM secretion on the mechanical properties of hybrid polyester scaffolds. The scaffolds were synthesized from blends of fast degrading polyglycerol sebacate (PGS) and slowly degrading polycaprolactone (PCL). PGS–PCL scaffolds were electrospun using a 2:1 ratio of PGS to PCL. Accelerated hydrolytic degradation in 0.1mM sodium hydroxide revealed 2-fold faster degradation of PGS–PCL scaffolds compared with PCL scaffolds. Thermal analysis and scanning electron microscopy demonstrated marginal change in PCL scaffold properties, while PGS–PCL scaffolds showed preferential mass loss of PGS and thinning of the individual fibers during degradation. Consequently, the mechanical properties of PGS–PCL scaffolds decreased gradually with no significant change for PCL scaffolds during accelerated degradation. Valvular interstitial cells (VICs) seeded on PGS–PCL scaffolds showed higher ECM protein secretion compared with PCL. Thus the mechanical properties of the cell-seeded PCL scaffolds did not change significantly compared with acellular scaffolds, probably due to slower degradation and ECM deposition by VICs. In contrast, the PGS–PCL scaffolds exhibited a gradual decrease in the mechanical properties of the acellular scaffolds due to degradation, which was compensated for by new matrix secreted by VICs seeded on the scaffolds. Our study demonstrated that the faster degrading PGS component of PGS–PCL accelerated the degradation rate of the scaffolds. VICs, on the other hand, were able to remodel the synthetic scaffold, depositing new matrix proteins and maintaining the mechanical properties of the scaffolds. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
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50. Transparent, elastomeric and tough hydrogels from poly(ethylene glycol) and silicate nanoparticles.
- Author
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Gaharwar, Akhilesh K., Rivera, Christian P., Wu, Chia-Jung, and Schmidt, Gudrun
- Subjects
HYDROGELS ,NANOCOMPOSITE materials ,ELASTOMERS ,TRANSPARENCY (Optics) ,POLYETHYLENE glycol ,SILICATES ,MECHANICAL properties of polymers ,PHOTOPOLYMERIZATION - Abstract
Abstract: The structures and mechanical properties of both physically and covalently cross-linked nanocomposite hydrogels made from poly(ethylene glycol) (PEG) and silicate nanoparticles (Laponite RD) are investigated. Injectable nanocomposite precursor solutions can be covalently cross-linked via photopolymerization. The resulting hydrogels are transparent and have interconnected pores, high elongation and toughness. These properties depend on the hydrogel composition, polymer–nanoparticle interactions and degree of cross-linking (both physical and covalent). Covalent cross-linking of polymer chains leads to the formation of an elastic network, whereas physical cross-linking between nanoparticles and polymer chains induces viscoelastic properties. At high deformations covalent bonds may be broken but physical bonds rebuild and to some extent self-heal the overall network structure. Addition of silicate also enhances the bioactivity and adhesiveness of the hydrogel as these materials stick to soft tissue as well as to hard surfaces. In addition, MC3T3-E1 mouse preosteoblast cells readily adhere and spread on nanocomposite hydrogel surfaces. Collectively, the combinations of properties such as elasticity, stiffness, interconnected network, adhesiveness to surfaces and bio-adhesion to cells provide inspiration and opportunities to engineer mechanically strong and elastic tissue matrixes for orthopedic, craniofacial and dental applications. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
- View/download PDF
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