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

Now showing 1 - 10 of 29
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    Anisotropic Elastography for Local Passive Properties and Active Contractility of Myocardium from Dynamic Heart Imaging Sequence
    (Hindawi, 2006) Liu, Yi; Wang, Ge; Sun, L. Z.; Biomedical Engineering, Purdue School of Engineering and Technology
    Major heart diseases such as ischemia and hypertrophic myocardiopathy are accompanied with significant changes in the passive mechanical properties and active contractility of myocardium. Identification of these changes helps diagnose heart diseases, monitor therapy, and design surgery. A dynamic cardiac elastography (DCE) framework is developed to assess the anisotropic viscoelastic passive properties and active contractility of myocardial tissues, based on the chamber pressure and dynamic displacement measured with cardiac imaging techniques. A dynamic adjoint method is derived to enhance the numerical efficiency and stability of DCE. Model-based simulations are conducted using a numerical left ventricle (LV) phantom with an ischemic region. The passive material parameters of normal and ischemic tissues are identified during LV rapid/reduced filling and artery contraction, and those of active contractility are quantified during isovolumetric contraction and rapid/reduced ejection. It is found that quasistatic simplification in the previous cardiac elastography studies may yield inaccurate material parameters.
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    Crosslinking and degradation of step-growth hydrogels formed by thiol-ene photo-click chemistry
    (ACS, 2012) Shih, Han; Lin, Chien-Chi; Biomedical Engineering, Purdue School of Engineering and Technology
    Thiol-ene photoclick hydrogels have been used for a variety of tissue engineering and controlled release applications. In this step-growth photopolymerization scheme, four-arm poly(ethylene glycol) norbornene (PEG4NB) was cross-linked with dithiol containing cross-linkers to form chemically cross-linked hydrogels. While the mechanism of thiol-ene gelation was well described in the literature, its network ideality and degradation behaviors are not well-characterized. Here, we compared the network cross-linking of thiol-ene hydrogels to Michael-type addition hydrogels and found thiol-ene hydrogels formed with faster gel points and higher degree of cross-linking. However, thiol-ene hydrogels still contained significant network nonideality, demonstrated by a high dependency of hydrogel swelling on macromer contents. In addition, the presence of ester bonds within the PEG-norbornene macromer rendered thiol-ene hydrogels hydrolytically degradable. Through validating model predictions with experimental results, we found that the hydrolytic degradation of thiol-ene hydrogels was not only governed by ester bond hydrolysis, but also affected by the degree of network cross-linking. In an attempt to manipulate network cross-linking and degradation of thiol-ene hydrogels, we incorporated peptide cross-linkers with different sequences and characterized the hydrolytic degradation of these PEG-peptide hydrogels. In addition, we incorporated a chymotrypsin-sensitive peptide as part of the cross-linkers to tune the mode of gel degradation from bulk degradation to surface erosion.
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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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    Differential Activation and Inhibition of RhoA by Fluid Flow Induced Shear Stress in Chondrocytes
    (Wiley, 2013) Wan, Qiaoqiao; Kim, Seung Joon; Yokota, Hiroki; Na, Sungsoo; Biomedical Engineering, Purdue School of Engineering and Technology
    Physical force environment is a major factor that influences cellular homeostasis and remodelling. It is not well understood, however, as a potential role of force intensities in the induction of cellular mechanotransduction. Using a fluorescence resonance energy transfer-based approach, we asked whether activities of GTPase RhoA in chondrocytes are dependent on intensities of flow-induced shear stress. We hypothesized that RhoA activities can be either elevated or reduced by selecting different levels of shear-stress intensities. The result indicates that C28/I2 chondrocytes have increased RhoA activities in response to high shear stress (10 or 20 dyn/cm(2) ), whereas a decrease in activity was seen with an intermediate shear stress of 5 dyn/cm(2) . No changes were seen under low shear stress (2 dyn/cm(2) ). The observed two-level switch of RhoA activities is closely linked to the shear-stress-induced alterations in actin cytoskeleton and traction forces. In the presence of constitutively active RhoA (RhoA-V14), intermediate shear stress suppressed RhoA activities, while high shear stress failed to activate them. In chondrocytes, expression of various metalloproteinases is, in part, regulated by shear and normal stresses through a network of GTPases. Collectively, the data suggest that intensities of shear stress are critical in differential activation and inhibition of RhoA activities in chondrocytes.
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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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    Dynamic force-induced direct dissociation of protein complexes in a nuclear body in living cells
    (Springer Nature, 2012-05-29) Poh, Yeh-Chuin; Shevtsov, Sergey P.; Chowdhury, Farhan; Wu, Douglas C.; Na, Sungsoo; Dundr, Miroslav; Wang, Ning; Biomedical Engineering, Purdue School of Engineering and Technology
    Despite past progress in understanding mechanisms of cellular mechanotransduction, it is unclear whether a local surface force can directly alter nuclear functions without intermediate biochemical cascades. Here we show that a local dynamic force via integrins results in direct displacements of coilin and SMN proteins in Cajal bodies and direct dissociation of coilin-SMN associated complexes. Spontaneous movements of coilin increase more than those of SMN in the same Cajal body after dynamic force application. Fluorescence resonance energy transfer changes of coilin-SMN depend on force magnitude, an intact F-actin, cytoskeletal tension, Lamin A/C, or substrate rigidity. Other protein pairs in Cajal bodies exhibit different magnitudes of fluorescence resonance energy transfer. Dynamic cyclic force induces tiny phase lags between various protein pairs in Cajal bodies, suggesting viscoelastic interactions between them. These findings demonstrate that dynamic force-induced direct structural changes of protein complexes in Cajal bodies may represent a unique mechanism of mechanotransduction that impacts on nuclear functions involved in gene expression.
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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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    Effect of shear stress and substrate on endothelial DAPK expression, caspase activity, and apoptosis
    (Springer Nature, 2013-01-10) Rennier, Keith; Ji, Julie Y.; Biomedical Engineering, Purdue School of Engineering and Technology
    Background: In the vasculature, misdirected apoptosis in endothelial cells leads to pathological conditions such as inflammation. Along with biochemical and molecular signals, the hemodynamic forces that the cells experience are also important regulators of endothelial functions such as proliferation and apoptosis. Laminar shear stress inhibits apoptosis induced by serum depletion, oxidative stress, and tumor necrosis factor α (TNFα). Death associated protein kinase (DAPK) is a positive regulator of TNFα induced apoptotic pathway. Here we investigate the effect of shear stress on DAPK in endothelial cells on glass or silicone membrane substrate. We have already shown a link between shear stress and DAPK expression and apoptosis in cells on glass. Here we transition our study to endothelial cells on non-glass substrates, such as flexible silicone membrane used for cyclic strain studies. Results: We modified the classic parallel plate flow chamber to accommodate silicone membrane as substrate for cells, and validated the chamber for cell viability in shear stress experiments. We found that adding shear stress significantly suppressed TNFα induced apoptosis in cells; while shearing cells alone also increased apoptosis on either substrate. We also found that shearing cells at 12 dynes/cm2 for 6 hours resulted in increased apoptosis on both substrates. This shear-induced apoptosis correlated with increased caspase 3/7 activities and DAPK expression and activation via dephosphorylation of serine 308. Conclusion: These data suggest that shear stress induced apoptosis in endothelial cells via increased DAPK expression and activation as well as caspase-3/7 activity. Most in vitro shear stress studies utilize the conventional parallel plate flow chamber where cells are cultured on glass, which is much stiffer than what cells encounter in vivo. Other mechanotransduction studies have utilized the flexible silicone membrane as substrate, for example, in cyclic stretch studies. Thus, this study bridges the gap between shear stress studies on cells plated on glass to studies on different stiffness of substrates or mechanical stimulation such as cyclic strain. We continue to explore the mechanotransduction role of DAPK in endothelial apoptosis, by using substrates of physiological stiffness for shear stress studies, and by using silicone substrate in cyclic stretch devices.
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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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    Fast-Relaxing Hydrogels with Reversibly Tunable Mechanics for Dynamic Cancer Cell Culture
    (Elsevier, 2024) Khine, Yee Yee; Nguyen, Han; Afolabi, Favour; Lin, Chien-Chi; Biomedical Engineering, Purdue School of Engineering and Technology
    The mechanics of the tumor microenvironment (TME) significantly impact disease progression and the efficacy of anti-cancer therapeutics. While it is recognized that advanced in vitro cancer models will benefit cancer research, none of the current engineered extracellular matrices (ECM) adequately recapitulate the highly dynamic TME. Through integrating reversible boronate-ester bonding and dithiolane ring-opening polymerization, we fabricated synthetic polymer hydrogels with tumor-mimetic fast relaxation and reversibly tunable elastic moduli. Importantly, the crosslinking and dynamic stiffening of matrix mechanics were achieved in the absence of a photoinitiator, often the source of cytotoxicity. Central to this strategy was Poly(PEGA-co-LAA-co-AAPBA) (PELA), a highly defined polymer synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. PELA contains dithiolane for initiator-free gel crosslinking, stiffening, and softening, as well as boronic acid for complexation with diol-containing polymers to give rise to tunable viscoelasticity. PELA hydrogels were highly cytocompatible for dynamic culture of patient-derived pancreatic cancer cells. It was found that the fast-relaxing matrix induced mesenchymal phenotype of cancer cells, and dynamic matrix stiffening restricted tumor spheroid growth. Moreover, this new dynamic viscoelastic hydrogel system permitted sequential stiffening and softening to mimic the physical changes of TME.