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Browsing by Subject "Calcium phosphate"
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Item Collagen fibrils and cell nuclei are entrapped within Randall's plaques but not in CaOx matrix overgrowth: A microscopic inquiry into Randall's plaque stone pathogenesis(Wiley, 2022) Canela, Victor Hugo; Bledsoe, Sharon B.; Worcester, Elaine M.; Lingeman, James E.; El-Achkar, Tarek M.; Williams, James C., Jr.; Anatomy, Cell Biology and Physiology, School of MedicineCalcium oxalate (CaOx) stones can grow attached to the renal papillary calcification known as Randall's plaque. Although stone growth on Randall's plaque is a common phenomenon, this mechanism of stone formation is still poorly understood. The objective of this study was to investigate the microenvironment of mature Randall's plaque, explore its molecular composition and differentiate plaque from CaOx overgrowth using multimodal imaging on demineralized stone sections. Fluorescence imaging showed consistent differences in autofluorescence patterns between Randall's plaque and calcium oxalate overgrowth regions. Second harmonic generation imaging established the presence of collagen only in regions of decalcified Randall's plaque but not in regions of CaOx overgrowth matrix. Surprisingly, in these stone sections we observed cell nuclei with preserved morphology within regions of mature Randall's plaque. These conserved cells had variable expression of vimentin and CD45. The presence of nuclei in mature plaque indicates that mineralization is not necessarily associated with cell death. The markers identified suggest that some of the entrapped cells may be undergoing dedifferentiation or could emanate from a mesenchymal or immune origin. We propose that entrapped cells may play an important role in the growth and maintenance of Randall's plaque. Further characterization of these cells and thorough analyses of the mineralized stone forming renal papilla will be fundamental in understanding the pathogenesis of Randall's plaque and CaOx stone formation.Item Three-Dimensional Printing of Clinical Scale and Personalized Calcium Phosphate Scaffolds for Alveolar Bone Reconstruction(Elsevier, 2022) Anderson, Margaret; Dubey, Nileshkumar; Bogie, Kath; Cao, Chen; Li, Junying; Lerchbacker, Joseph; Mendonça, Gustavo; Kauffman, Frederic; Bottino, Marco C.; Kaigler, Darnell; Biomedical and Applied Sciences, School of DentistryObjective: Alveolar bone defects can be highly variable in their morphology and, as the defect size increases, they become more challenging to treat with currently available therapeutics and biomaterials. This investigation sought to devise a protocol for fabricating customized clinical scale and patient-specific, bioceramic scaffolds for reconstruction of large alveolar bone defects. Methods: Two types of calcium phosphate (CaP)-based bioceramic scaffolds (alginate/β-TCP and hydroxyapatite/α-TCP, hereafter referred to as hybrid CaP and Osteoink™, respectively) were designed, 3D printed, and their biocompatibility with alveolar bone marrow stem cells and mechanical properties were determined. Following scaffold optimization, a workflow was developed to use cone beam computed tomographic (CBCT) imaging to design and 3D print, defect-specific bioceramic scaffolds for clinical-scale bone defects. Results: Osteoink™ scaffolds had the highest compressive strength when compared to hybrid CaP with different infill orientation. In cell culture medium, hybrid CaP degradation resulted in decreased pH (6.3) and toxicity to stem cells; however, OsteoInk™ scaffolds maintained a stable pH (7.2) in culture and passed the ISO standard for cytotoxicity. Finally, a clinically feasible laboratory workflow was developed and evaluated using CBCT imaging to engineer customized and defect-specific CaP scaffolds using OsteoInk™. It was determined that printed scaffolds had a high degree of accuracy to fit the respective clinical defects for which they were designed (0.27 mm morphological deviation of printed scaffolds from digital design). Significance: From patient to patient, large alveolar bone defects are difficult to treat due to high variability in their complex morphologies and architecture. Our findings shows that Osteoink™ is a biocompatible material for 3D printing of clinically acceptable, patient-specific scaffolds with precision-fit for use in alveolar bone reconstructive procedures. Collectively, emerging digital technologies including CBCT imaging, 3D surgical planning, and (bio)printing can be integrated to address this unmet clinical challenge.Item Variability in stone composition and metabolic correlation between kidneys in patients with bilateral nephrolithiasis(Elsevier, 2019-12-20) Rivera, Marcelino E.; Nottingham, Charles U.; Borofsky, Michael S.; Kissel, Suzanne M.; Maniar, Viraj; Dauw, Casey A.; York, Nadya E.; Krambeck, Amy E.; Lingeman, James E.; Urology, School of MedicineIntroduction: To evaluate the clinical significance of discordant stone analyses in patients undergoing bilateral ureteroscopy. Methods: A retrospective chart review was performed for all patients undergoing stone extraction with bilateral ureteroscopy at our institution in an aim to identify patients who had bilateral stone analysis and 24-hour urine chemistry data available. Stones were then classified based upon the dominant present (>50%). Twenty-four hour urinalysis results were reviewed and statistical analysis performed comparing discordant and concordant patient populations, assessing significant differences that would potentially influence clinical management. Results: We identified 79 patients (158 renal units) who had bilateral stones removed at the time of ureteroscopy. The majority of stones were classified as calcium oxalate (CaOx) (60.1%) followed by calcium phosphate (CaP) (27.8%), brushite (5.1%), uric acid (UA) (4.4%) and cystine (2.5%). Discrepancies in stone classifications were present 24% of the time. Evaluation of 24-hour urinalysis results demonstrated that patients with CaOx:CaP stone discordance compared to CaOx:CaOx concordant stone formers were more likely to have an elevated pH (p=0.02) and lower uric acid supersaturation (p=0.01). Conclusions: Discrepancies in stone mineral content are common in patients with bilateral stone disease. A single stone analysis from one side in the setting of bilateral stone disease is insufficient for management of patients with bilateral renal stones, and may lead to mismanagement when this misrepresented information is utilized in addition to 24-hour urinalysis results. At least one stone analysis should be performed from both sides during a bilateral stone extraction procedure.