Browsing by Author "Chen, J."

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    Compression-induced structural and mechanical changes of fibrin-collagen composites
    (Elsevier, 2017-07) Kim, O. V.; Litvinov, R. I.; Chen, J.; Chen, D. Z.; Weisel, J.W.; Alber, M. S.; Medicine, School of Medicine
    Fibrin and collagen as well as their combinations play an important biological role in tissue regeneration and are widely employed in surgery as fleeces or sealants and in bioengineering as tissue scaffolds. Earlier studies demonstrated that fibrin-collagen composite networks displayed improved tensile mechanical properties compared to the isolated protein matrices. Unlike previous studies, here unconfined compression was applied to a fibrin-collagen filamentous polymer composite matrix to study its structural and mechanical responses to compressive deformation. Combining collagen with fibrin resulted in formation of a composite hydrogel exhibiting synergistic mechanical properties compared to the isolated fibrin and collagen matrices. Specifically, the composite matrix revealed a one order of magnitude increase in the shear storage modulus at compressive strains>0.8 in response to compression compared to the mechanical features of individual components. These material enhancements were attributed to the observed structural alterations, such as network density changes, an increase in connectivity along with criss-crossing, and bundling of fibers. In addition, the compressed composite collagen/fibrin networks revealed a non-linear transformation of their viscoelastic properties with softening and stiffening regimes. These transitions were shown to depend on protein concentrations. Namely, a decrease in protein content drastically affected the mechanical response of the networks to compression by shifting the onset of stiffening to higher degrees of compression. Since both natural and artificially composed extracellular matrices experience compression in various (patho)physiological conditions, our results provide new insights into the structural biomechanics of the polymeric composite matrix that can help to create fibrin-collagen sealants, sponges, and tissue scaffolds with tunable and predictable mechanical properties.
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    Conversion From Tacrolimus to Belatacept to Prevent the Progression of Chronic Kidney Disease in Pancreas Transplantation: Case Report of Two Patients
    (Wiley, 2014-11) Mujtaba, M. A.; Sharfuddin, A. A.; Taber, T.; Chen, J.; Phillips, C. L.; Goble, M.; Fridell, J. A.; Medicine, School of Medicine
    Belatacept is a novel immunosuppressive agent that may be used as an alternative to calcineurin inhibitors (CNI) in immunosuppression (IS) regimens. We report two cases of pancreas transplant that were switched from tacrolimus (TAC) to belatacept. Case 1: 38‐year‐old female with pancreas transplant alone maintained on TAC‐based IS regimen whose serum creatinine (SCr) slowly deteriorated from 0.6 mg/dL at baseline to 2.2 mg/dL, 16 months posttransplant. A native kidney biopsy performed showed CNI toxicity. The patient was started on belatacept and TAC was eliminated. Case 2: 49‐year‐old female with simultaneous pancreas–kidney transplant, maintained on TAC‐based regimen where the SCr worsened over an initial 3‐month period from a baseline of 1.0 to 3.0 mg/dL. Belatacept was started and TAC was lowered. Due to persistent graft dysfunction and kidney transplant biopsy still showing changes consistent with CNI toxicity, the TAC was then discontinued. At >1 year postbelatacept and off TAC follow‐up, kidney function as measured by SCr remains stable at 1.0 ± 0.2 mg/dL in both recipients. Neither patient developed rejection following the switch, and pancreas allograft function remains stable in both recipients.
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    Mechanical environment change in root, periodontal ligament, and alveolar bone in response to two canine retraction treatment strategies
    (Wiley Blackwell (Blackwell Publishing), 2015-04) Jiang, F.; Xia, Z.; Li, S.; Eckert, G.; Chen, J.; Department of Engineering Technology, School of Engineering and Technology
    OBJECTIVE: To investigate the initial mechanical environment (ME) changes in root surface, periodontal ligament (PDL), and alveolar bone due to two treatment strategies, low or high moment-to-force ratio (M/F). SETTING AND SAMPLE POPULATION: Indiana University-Purdue University Indianapolis. Eighteen patients who underwent maxillary bilateral canine retraction. MATERIAL AND METHOD: Finite element models of the maxillary canines from the patients were built based on their cone beam computed tomography scans. For each patient, the canine on one side had a specially designed T-loop spring with the M/F higher than the other side. Four stress invariants (1st principal/dilatational/3rd principal/von Mises stress) in the tissues were calculated. The stresses were compared with the bone mineral density (BMD) changes reported previously for linking the ME change to bone modeling/remodeling activities. The correlation was tested by the mixed-model anova. RESULTS: The alveolar bone in the direction of tooth movement is primarily in tension, while the PDL is in compression; the stresses in the opposite direction have a reversed pattern. The M/F primarily affects the stress in root. Three stress invariants (1st principal/3rd principal/dilatational stress) in the tooth movement direction have moderate correlations with BMD loss. CONCLUSIONS: The stress invariants may be used to characterize what the osteocytes sense when ME changes. Their distributions in the tissues are significantly different, meaning the cells experience different stimuli. The higher bone activities along the direction of tooth movement may be related to the initial volumetric increase and decrease in the alveolar bone.
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    Molecular Basis for Craniofacial Phenotypes Caused by Sclerostin Deletion
    (Sage, 2021) Chen, J.; Yuan, X.; Pilawski, I.; Liu, X.; Delgado-Calle, J.; Bellido, T.; Turkkahraman, H.; Helms, J.A.; Medicine, School of Medicine
    Some genetic disorders are associated with distinctive facial features, which can aid in diagnosis. While considerable advances have been made in identifying causal genes, relatively little progress has been made toward understanding how a particular genotype results in a characteristic craniofacial phenotype. An example is sclerosteosis/van Buchem disease, which is caused by mutations in the Wnt inhibitor sclerostin (SOST). Affected patients have a high bone mass coupled with a distinctive appearance where the mandible is enlarged and the maxilla is foreshortened. Here, mice carrying a null mutation in Sost were analyzed using quantitative micro-computed tomographic (µCT) imaging and histomorphometric analyses to determine the extent to which the size and shape of craniofacial skeleton were altered. Sost-/- mice exhibited a significant increase in appositional bone growth, which increased the height and width of the mandible and reduced the diameters of foramina. In vivo fluorochrome labeling, histology, and immunohistochemical analyses indicated that excessive bone deposition in the premaxillary suture mesenchyme curtailed overall growth, leading to midfacial hypoplasia. The amount of bone extracellular matrix produced by Sost-/- cells was significantly increased; as a consequence, osteoid seams were evident throughout the facial skeleton. Collectively, these analyses revealed a remarkable fidelity between human characteristics of sclerosteosis/van Buchem disease and the Sost-/- phenotype and provide clues into the conserved role for sclerostin signaling in modulating craniofacial morphology.
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    Wnt/β-catenin Signaling Controls Maxillofacial Hyperostosis
    (Sage, 2022) Chen, J.; Cuevas, P. L.; Dworan, J. S.; Dawid, I.; Turkkahraman, H.; Tran, K.; Delgado-Calle, J.; Bellido, T.; Gorski, J. P.; Liu, B.; Brunski, J. B.; Helms, J. A.; Orthodontics and Oral Facial Genetics, School of Dentistry
    The roles of Wnt/β-catenin signaling in regulating the morphology and microstructure of craniomaxillofacial (CMF) bones was explored using mice carrying a constitutively active form of β-catenin in activating Dmp1-expressing cells (e.g., daβcatOt mice). By postnatal day 24, daβcatOt mice exhibited midfacial truncations coupled with maxillary and mandibular hyperostosis that progressively worsened with age. Mechanistic insights into the basis for the hyperostotic facial phenotype were gained through molecular and cellular analyses, which revealed that constitutively activated β-catenin in Dmp1-expressing cells resulted in an increase in osteoblast number and an increased rate of mineral apposition. An increase in osteoblasts was accompanied by an increase in osteocytes, but they failed to mature. The resulting CMF bone matrix also had an abundance of osteoid, and in locations where compact lamellar bone typically forms, it was replaced by porous, woven bone. The hyperostotic facial phenotype was progressive. These findings identify for the first time a ligand-independent positive feedback loop whereby unrestrained Wnt/β-catenin signaling results in a CMF phenotype of progressive hyperostosis combined with architecturally abnormal, poorly mineralized matrix that is reminiscent of craniotubular disorders in humans.