Browsing by Author "Mikos, Antonios"
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Item Design and Characterization of a Thermogelling Ink and Support Bath System for Extrusion Bioprinting(2023-04-18) Navara, Adam; Mikos, AntoniosThree-dimensional (3D) printing methodologies are growing increasingly popular for fabricating tissue engineering constructs, due to their ability to efficiently and repeatably produce highly complex and patient-specific designs. Of particularly common use is extrusion printing, as it can be used with many pre-existing hydrogel materials due to the more readily compatible rheological and chemical requirements. However, extrusion printing is also associated with the lowest resolution and cellular compatibility of the 3D printing methodologies. Recent innovations in hydrogel support baths have addressed some of these concerns, but the versatility of the studied support materials is limited, as is the understanding of their physical relationship with the ink they support. This work presents the adaptation of a poly(N-isopropylacrylamide)-based thermogelling macromer (TGM) for extrusion printing through the inclusion of a poloxamer hydrogel support bath. Material and instrument factors were assessed for their effect on printability and fiber size. Due to the unique dual-gelling nature of the TGM ink, uniform scaffolds can be fabricated consisting of TGM hydrogel fibers with tunable diameters between 80 and 200 μm. In addition, material and instrument factors were also studied for their effect on printed chondrocyte viability. It was determined that printed TGM scaffolds could support viable chondrocytes while maintaining good resolution and uniformity. Finally, the physical relationship between the ink and the support bath, and the dynamic nature of the bath’s rheological properties, were illuminated, contributing to our understanding of this bioprinting methodology.Item Revolutionizing bone regeneration: advanced biomaterials for healing compromised bone defects(Frontiers Media S.A., 2023) Awad, Kamal; Ahuja, Neelam; Yacoub, Ahmed S.; Brotto, Leticia; Young, Simon; Mikos, Antonios; Aswath, Pranesh; Varanasi, VenuIn this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the declining rate of new bone formation associated with age-related changes in the skeletal system. This article emphasizes the importance of semiconductor industry-derived materials as a potential solution to combat oxidative stress and address the challenges associated with aging bone. Furthermore, we discuss various material and autologous treatment approaches, as well as in vitro and in vivo models used to investigate new therapeutic strategies in the context of craniofacial bone repair. By focusing on these aspects, we aim to shed light on the potential of advanced biomaterials to overcome the limitations of current treatments and pave the way for more effective and efficient therapeutic interventions for craniofacial bone defects.Item SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via Nuclear Erythroid Factor 2 Activity under Toxic Oxidative Stress Conditions(MDPI, 2024) Ahuja, Neelam; Awad, Kamal; Yang, Su; Dong, He; Mikos, Antonios; Aswath, Pranesh; Young, Simon; Brotto, Marco; Varanasi, Venu; Center for Engineering Complex Tissues; Center for Excellence in Tissue EngineeringHealing in compromised and complicated bone defects is often prolonged and delayed due to the lack of bioactivity of the fixation device, secondary infections, and associated oxidative stress. Here, we propose amorphous silicon oxynitride (SiONx) as a coating for the fixation devices to improve both bioactivity and bacteriostatic activity and reduce oxidative stress. We aimed to study the effect of increasing the N/O ratio in the SiONx to fine-tune the cellular activity and the antioxidant effect via the NRF2 pathway under oxidative stress conditions. The in vitro studies involved using human mesenchymal stem cells (MSCs) to examine the effect of SiONx coatings on osteogenesis with and without toxic oxidative stress. Additionally, bacterial growth on SiONx surfaces was studied using methicillin-resistant Staphylococcus aureus (MRSA) colonies. NRF2 siRNA transfection was performed on the hMSCs (NRF2-KD) to study the antioxidant response to silicon ions. The SiONx implant surfaces showed a >4-fold decrease in bacterial growth vs. bare titanium as a control. Increasing the N/O ratio in the SiONx implants increased the alkaline phosphatase activity >1.5 times, and the other osteogenic markers (osteocalcin, RUNX2, and Osterix) were increased >2-fold under normal conditions. Increasing the N/O ratio in SiONx enhanced the protective effects and improved cell viability against toxic oxidative stress conditions. There was a significant increase in osteocalcin activity compared to the uncoated group, along with increased antioxidant activity under oxidative stress conditions. In NRF2-KD cells, there was a stunted effect on the upregulation of antioxidant markers by silicon ions, indicating a role for NRF2. In conclusion, the SiONx coatings studied here displayed bacteriostatic properties. These materials promoted osteogenic markers under toxic oxidative stress conditions while also enhancing antioxidant NRF2 activity. These results indicate the potential of SiONx coatings to induce in vivo bone regeneration in a challenging oxidative stress environment.