Browsing by Author "Biomedical Engineering, Purdue School of Engineering and Technology"

Now showing 1 - 10 of 21
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    Degradable and Multifunctional PEG-Based Hydrogels Formed by iEDDA Click Chemistry with Stable Click-Induced Supramolecular Interactions
    (American Chemical Society, 2024-02-16) Dimmitt, Nathan H.; Lin, Chien-Chi; Biomedical Engineering, Purdue School of Engineering and Technology
    The inverse electron demand Diels-Alder (iEDDA) reactions are highly efficient click chemistry increasingly utilized in bioconjugation, live cell labeling, and the synthesis and modification of biomaterials. iEDDA click reactions have also been used to cross-link tetrazine (Tz) and norbornene (NB) modified macromers [e.g., multiarm poly(ethylene glycol) or PEG]. In these hydrogels, Tz-NB adducts exhibit stable supramolecular interactions with a high hydrolytic stability. Toward engineering a new class of PEG-based click hydrogels with highly adaptable properties, we previously reported a new group of NB-derivatized PEG macromers via reacting hydroxyl-terminated PEG with carbic anhydride (CA). In this work, we show that c cross-linked by PEGNBCA or its derivatives exhibited fast and tunable hydrolytic degradation. Here, we show that PEGNBCA (either mono- or octafunctional) and its dopamine or tyramine conjugated derivatives (i.e., PEGNB-D and PEGNB-T) readily cross-link with 4-arm PEG-Tz to form a novel class of multifunctional iEDDA click hydrogels. Through modularly adjusting the macromers with unstable and stable iEDDA click-induced supramolecular interactions (iEDDA-CSI), we achieved highly tunable degradation, with full degradation in less than 2 weeks to over two months. We also show that secondary enzymatic reactions could dynamically stiffen these hydrogels. These hydrogels could also be spatiotemporally photopatterned through visible light-initiated photochemistry. Finally, the iEDDA-CSI hydrogels post ester hydrolysis displayed shear-thinning and self-healing properties, enabling injectable delivery.
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    Digital Light Processing 3D Bioprinting of Gelatin-Norbornene Hydrogel for Enhanced Vascularization
    (Wiley, 2023) Duong, Van Thuy; Lin, Chien-Chi; Biomedical Engineering, Purdue School of Engineering and Technology
    Digital light processing (DLP) bioprinting can be used to fabricate volumetric scaffolds with intricate internal structures, such as perfusable vascular channels. The successful implementation of DLP bioprinting in tissue fabrication requires using suitable photo-reactive bioinks. Norbornene-based bioinks have emerged as an attractive alternative to (meth)acrylated macromers in 3D bioprinting owing to their mild and rapid reaction kinetics, high cytocompatibility for in situ cell encapsulation, and adaptability for post-printing modification or conjugation of bioactive motifs. In this contribution, the development of gelatin-norbornene (GelNB) is reported as a photo-cross-linkable bioink for DLP 3D bioprinting. Low concentrations of GelNB (2-5 wt.%) and poly(ethylene glycol)-tetra-thiol (PEG4SH) are DLP-printed with a wide range of stiffness (G' ≈120 to 4000 Pa) and with perfusable channels. DLP-printed GelNB hydrogels are highly cytocompatible, as demonstrated by the high viability of the encapsulated human umbilical vein endothelial cells (HUVECs). The encapsulated HUVECs formed an interconnected microvascular network with lumen structures. Notably, the GelNB bioink permitted both in situ tethering and secondary conjugation of QK peptide, a vascular endothelial growth factor (VEGF)-mimetic peptide. Incorporation of QK peptide significantly improved endothelialization and vasculogenesis of the DLP-printed GelNB hydrogels, reinforcing the applicability of this bioink system in diverse biofabrication applications.
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    Effect of elastic modulus of tumour and non-tumour cells on vibration-induced behaviours
    (Springer Nature, 2025-04-16) Ku, BonHeon; Liu, Jing; Na, Sungsoo; Yokota, Hiroki; Hong, Chinsuk; Lim, HeeChang; Biomedical Engineering, Purdue School of Engineering and Technology
    The mechanical behaviour of tumour and non-tumour cells under vibration remains insufficiently explored, particularly the role of elastic modulus in dynamic responses. This study investigates the vibration-induced mechanical behaviour in cellular structures with varying elastic moduli (E = 0.1 , 1 , and 10 kPa) and aspect ratios ([Formula: see text] and 4), focusing on vertical and horizontal forced vibrations. Finite element analysis was conducted to evaluate the natural frequencies, mode shapes, membrane accelerations, and stress responses. The intermediate aspect-ratio structures ([Formula: see text]) exhibited higher natural frequencies but a 64.2% increase in stress concentration, making them more susceptible to localised deformation under resonance. Conversely, higher aspect-ratio structures ([Formula: see text]) demonstrated improved vibrational stability with reduced resonance peaks and 64.6% lower localised stress. This study further confirmed that vertical vibrations generate higher stress and acceleration than horizontal vibrations owing to gravitational effects. Stress contour analysis indicated that under low-intensity vibrations, intermediate aspect-ratio structures may exceed their yield stress thresholds, leading to potential membrane rupture. These findings suggest that vibration-induced mechanical stimulation can be sensed differently depending on the elastic moduli and aspect ratios of tumour and non-tumour cells.
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    Facile preparation of photodegradable hydrogels by photopolymerization
    (Elsevier, 2013) Ki, Chang Seok; Shih, Han; Lin, Chien-Chi; Biomedical Engineering, Purdue School of Engineering and Technology
    Photodegradable hydrogels have emerged as a powerful material platform for studying and directing cell behaviors, as well as for delivering drugs. The premise of this technique is to use a cytocompatible light source to cleave linkers within a hydrogel, thus causing reduction of matrix stiffness or liberation of matrix-tethered biomolecules in a spatial-temporally controlled manner. The most commonly used photodegradable units are molecules containing nitrobenzyl moieties that absorb light in the ultraviolet (UV) to lower visible wavelengths (~280 to 450 nm). Because photodegradable linkers and hydrogels reported in the literature thus far are all sensitive to UV light, highly efficient UV-mediated photopolymerizations are less likely to be used as the method to prepare these hydrogels. As a result, currently available photodegradable hydrogels are formed by redox-mediated radical polymerizations, emulsion polymerizations, Michael-type addition reactions, or orthogonal click chemistries. Here, we report the first photodegradable poly(ethylene glycol)-based hydrogel system prepared by step-growth photopolymerization. The model photolabile peptide cross-linkers, synthesized by conventional solid phase peptide synthesis, contained terminal cysteines for step-growth thiol-ene photo-click reactions and a UV-sensitive 2-nitrophenylalanine residue in the peptide backbone for photo-cleavage. Photolysis of this peptide was achieved through adjusting UV light exposure time and intensity. Photopolymerization of photodegradable hydrogels containing photolabile peptide cross-linkers was made possible via a highly efficient visible light-mediated thiol-ene photo-click reaction using a non-cleavage type photoinitiator eosin-Y. Rapid gelation was confirmed by in situ photo-rheometry. Flood UV irradiation at controlled wavelength and intensity was used to demonstrate the photodegradability of these photopolymerized hydrogels.
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    Feeding the Kidney Researcher Pipeline through R25-NIDDK Funded Summer Undergraduate Research Fellowships: A Student Perspective
    (Wolters Kluwer, 2022-03-31) Wilson, Elena M.; Lipp, Sarah N.; Brady, Clayton T.; Ishibe, Shuta; Romero, Michael F.; Biomedical Engineering, Purdue School of Engineering and Technology
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    Gender Differences in Histamine-Induced Depolarization and Inward Currents in Vagal Ganglion Neurons in Rats
    (Ivyspring, 2013-11-20) Li, Jun-Nan; Qian, Zhao; Xu, Wen-Xiao; Xu, Bing; Lu, Xiao-Long; Yan, Zhen-Yu; Han, Li-Min; Liu, Yang; Yuan, Mei; Schild, John; Qiao, Guo-Fen; Li, Bai-Yan; Biomedical Engineering, Purdue School of Engineering and Technology
    Evidence has shown gender differences regarding the critical roles of histamine in the prevalence of asthma, anaphylaxis, and angina pectoris. Histamine depolarizes unmyelinated C-type neurons without any effects on myelinated A-type vagal ganglion neurons (VGNs) in male rats. However, little is known if VGNs from females react to histamine in a similar manner. Membrane depolarization and inward currents were tested in VGNs isolated from adult rats using a whole-cell patch technique. Results from males were consistent with the literature. Surprisingly, histamine-induced depolarization and inward currents were observed in both unmyelinated C-type and myelinated A- and Ah-type VGNs from female rats. In Ah-type neurons, responses to 1.0 μM histamine were stronger in intact females than in males and significantly reduced in ovariectomized (OVX) females. In C-type neurons, histamine-induced events were significantly smaller (pA/pF) in intact females compared with males and this histamine-induced activity was dramatically increased by OVX. Female A-types responded to histamine, which was further increased following ovariectomy. Histamine at 300 nM depolarized Ah-types in females, but not Ah-types in OVX females. In contrast, the sensitivity of A- and C-types to histamine was upregulated by OVX. These data demonstrate gender differences in VGN chemosensitivity to histamine for the first time. Myelinated Ah-types showed the highest sensitivity to histamine across female populations, which was changed by OVX. These novel findings improve the understanding of gender differences in the prevalence of asthma, anaphylaxis, and pain. Changes in sensitivity to histamine by OVX may explain alterations in the prevalence of certain pathophysiological conditions when women reach a postmenopausal age.
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    Geometric Characterization of Local Changes in Tungsten Microneedle Tips after In-Vivo Insertion into Peripheral Nerves
    (MDPI, 2022) Sergi, Pier Nicola; Jensen, Winnie; Yoshida, Ken; Biomedical Engineering, Purdue School of Engineering and Technology
    Peripheral neural interfaces are used to connect the peripheral nervous system to high-tech robotic devices and computer interfaces. Soft materials are nowadays used to build the main structural part of these interfaces because they are able to mimic the mechanical properties of peripheral nerves. However, if on the one hand soft materials provide effective connections, reducing mechanical mismatch with nervous tissues and creating a close contact between active sites and neural fibers, on the other hand, most of them are not mechanically stable during implantation. As a consequence, tungsten (W) microneedles are used to insert soft neural interfaces, because they are able to pierce the peripheral nervous tissue because of their high stiffness. Nevertheless, this stiffness cannot prevent microneedles from local microscopic structural damage, even after successful insertions. In addition, the nature of this damage is not totally clear. Therefore, this work aimed at quantitatively investigating the phenomenological changes of the microneedles’ tip shape after insertion into the in vivo peripheral nerves. In particular, a quantification of the interactions between peripheral nerves and W microneedles was proposed through the Oliver-Pharr formula, and the interaction force was found to be directly proportional to the power < m > = 2.124 of the normalized indentation depth. Moreover, an experimental correlation between insertion force and the opening tip angle was described together with an assessment of the minimum diameter to effectively puncture the peripheral nervous tissue. Finally, a computational framework was presented to describe the local changes affecting the microneedles’ tip shape. This approach was able to detect a bulging phenomenon along with the microneedle tips with a characteristic amplitude of approximately 100 μm, and a folding phenomenon, with a characteristic mean amplitude of less than 20 μm, affecting the extreme ending sections of the microneedle tips. These geometrical changes were related to the synergistic action of interaction forces likely resulting in compression and elastic instability of the tip.
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    Left atrial reservoir strain as a predictor of cardiac dysfunction in a murine model of pressure overload
    (Wiley, 2025) Salvas, John P.; Moore-Morris, Thomas; Goergen, Craig J.; Sicard, Pierre; Biomedical Engineering, Purdue School of Engineering and Technology
    Aim: Left atrial (LA) strain is emerging as a valuable metric for evaluating cardiac function, particularly under pathological conditions such as pressure overload. This preclinical study investigates the predictive utility of LA strain on cardiac function in a murine model subjected to pressure overload, mimicking pathologies such as hypertension and aortic stenosis. Methods: High-resolution ultrasound was performed in a cohort of mice (n = 16) to evaluate left atrial and left ventricular function at baseline and 2 and 4 weeks after transverse aortic constriction (TAC). Acute adaptations in cardiac function were assessed in a subgroup of mice (n = 10) with 3 days post-TAC imaging. Results: We report an increase in LA max volume from 11.0 ± 4.3 μL at baseline to 26.7 ± 16.7 μL at 4 weeks (p = 0.002) and a decrease in LA reservoir strain from 20.8 ± 5.4% at baseline to 10.2 ± 6.9% at 4 weeks (p = 0.001). In the acute phase, LA strain dysfunction was present at 3 days (p < 0.001), prior to alterations in LA volume (p = 0.856) or left ventricular (LV) ejection fraction (p = 0.120). LA reservoir strain correlated with key indicators of cardiac performance including left ventricular (LV) ejection fraction (r = 0.541, p < 0.001), longitudinal strain (r = -0.637, p < 0.001), and strain rate (r = 0.378, p = 0.007). Furthermore, markers of atrial structure and function including LA max volume (AUC = 0.813, p = 0.003), ejection fraction (AUC = 0.853, p = 0.001), and strain (AUC = 0.884, p < 0.001) all predicted LV dysfunction. Conclusion: LA strain and function assessments provide a reliable, non-invasive method for the early detection and prediction of cardiac dysfunction in a model of pressure overload.
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    Mechanical Loading Mitigates Osteoarthritis Symptoms by Regulating the Inflammatory Microenvironment
    (SSRN, 2021-06-14) Zhang, Weiwei; Li, Xinle; Li, Jie; Wang, Xiaoyu; Liu, Daquan; Zhai, Lidong; Ding, Beibei; Li, Guang; Sun, Yuting; Yokota, Hiroki; Zhang, Ping; Biomedical Engineering, Purdue School of Engineering and Technology
    Osteoarthritis (OA) is one of the most common chronic diseases, in which inflammatory responses in the articular cavity induce chondrocyte apoptosis and cartilage degeneration. While mechanical loading is reported to mitigate synovial inflammation, the mechanism and pathways for the loading-driven improvement of OA symptoms remain unclear. In this research, we evaluated the loading effects on the M1/M2 polarization of synovial macrophages via performing molecular, cytology, and histology analyses. In the OA groups, the cell layer of the synovial lining was enlarged with an increase in cell density. Also, M1 macrophages were polarized and pro-inflammatory cytokines were increased. In contrast, in the OA group with mechanical loading cartilage degradation was reduced and synovial inflammation was alleviated. Notably, the polarization of M1 macrophages was diminished by mechanical loading, while that of M2 macrophages was increased. Furthermore, mechanical loading decreased the levels of pro-inflammatory cytokines such as IL-1β and TNF-α and suppressed PI3K/AKT/NF-κB signaling. Consistently, NF-κB inhibited decreased the polarization of M1 macrophages in RAW264.7 macrophages. Taken together, this study demonstrates that mechanical loading changes the ratio of M1 and M2 macrophage polarization via regulating PI3K/AKT/NF-κB signaling and provides chondroprotective effects in the mouse OA model.
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    Numerical Simulation and Clinical Implications of Stenosis in Coronary Blood Flow
    (Hindawi, 2014) Zhang, Jun-Mei; Zhong, Liang; Luo, Tong; Huo, Yunlong; Tan, Swee Yaw; Wong, Aaron Sung Lung; Su, Boyang; Wan, Min; Zhao, Xiaodan; Kassab, Ghassan S.; Lee, Heow Pueh; Khoo, Boo Cheong; Kang, Chang-Wei; Ba, Te; Tan, Ru San; Biomedical Engineering, Purdue School of Engineering and Technology
    Fractional flow reserve (FFR) is the gold standard to guide coronary interventions. However it can only be obtained via invasive angiography. The objective of this study is to propose a noninvasive method to determine FFRCT by combining computed tomography angiographic (CTA) images and computational fluid dynamics (CFD) technique. Utilizing the method, this study explored the effects of diameter stenosis (DS), stenosis length, and location on FFRCT. The baseline left anterior descending (LAD) model was reconstructed from CTA of a healthy porcine heart. A series of models were created by adding an idealized stenosis (with DS from 45% to 75%, stenosis length from 4 mm to 16 mm, and at 4 locations separately). Through numerical simulations, it was found that FFRCT decreased (from 0.89 to 0.74), when DS increased (from 45% to 75%). Similarly, FFRCT decreased with the increase of stenosis length and the stenosis located at proximal position had lower FFRCT than that at distal position. These findings are consistent with clinical observations. Applying the same method on two patients' CTA images yielded FFRCT close to the FFR values obtained via invasive angiography. The proposed noninvasive computation of FFRCT is promising for clinical diagnosis of CAD.