7 research outputs found
Chitosan paste from crawfish shells as a synthetic bone graft material: Preparation, characterization and animal study
Bone loss associated with musculoskeletal trauma or metabolic diseases often requires bone grafts. Autograft or allograft bones are limited in supply. Therefore, development of synthetic bone graft materials is an active area of research. For several years the biomaterials group at LSUHSC-Shreveport has been investigating the use of chitosan purified from crawfish shells using a process patented by my research advisor, Dr. Debi Mukherjee.
Chitin is a polysaccharide that exists in fungi, exoskeleton of insects and outer shell of crustaceans. It is biocompatible, osteoconductive, antimicrobial, biodegradable, non-toxic, haemostatic, fungicidal, and the second most abundant natural polysaccharide on earth. Removal of the acetyl group from chitin forms chitosan. Chitosan is more useful due to the presence of amino groups that impart a positive charge to the molecule. This positive charge interacts with cells or can act as a binding site for other functional groups thereby expanding the role of chitosan molecules.
The objectives of this study are: (1) Test for the presence of bone in grafted and ungrafted defects and compare the results among the different groups. (2) Test and compare the differences in stiffnesses and fracture loads among the different groups. (3) Test, via microcomputed tomography, defect reduction in samples treated with the graft. (4) Test for the amorphous nature of crawfish chitosan. (5) Compare the purity of crawfish chitosan extracted using Dr. Debi Mukherjee\u27s procedure with commercially available chitosan.
The first portion of this experiment was characterization of crawfish chitosan, extracted using a method patented by Dr. Debi Mukherjee, to determine the individual chemical fingerprint of crawfish chitosan. Tests established that crawfish chitosan contains identical functional groups as chitosan monomer and chitosan glutamate and possessing an amorphous structure.
In the second portion of this study, purified chitosan was mixed with cultured osteoblasts and compounded with a calcium salt creating a bone graft paste. Eighteen male Lewis rats underwent the surgical procedure. A critical size defect was created in rat femurs following a published protocol and repaired through use of a metal plate with and without crawfish chitosan bone graft paste. Histological examination and bone graft analysis of defected areas demonstrated the presence of bone in defect areas that were filled with experimental paste material and reduced or no bone growth on control femurs.
Chitosan possesses the necessary properties, when combined with plaster of Paris and osteoblasts, to create a bone graft that is osteoconductive, osteoinductive and osteogenic
Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves
The calcification process in aortic stenosis has garnered considerable interest but only limited investigation into selected signaling pathways. This study investigated mechanisms related to hypoxia, hyaluronan homeostasis, brown adipocytic differentiation, and ossification within calcified valves. Surgically explanted calcified aortic valves (nï¾ =ï¾ 14) were immunostained for markers relevant to these mechanisms and evaluated in the center (NodCtr) and edge (NodEdge) of the calcified nodule (NodCtr), tissue directly surrounding nodule (NodSurr); center and tissue surrounding small モprenodulesï¾” (PreNod, PreNodSurr); and normal fibrosa layer (CollFibr). Pearson correlations were determined between staining intensities of markers within regions. Ossification markers primarily localized to NodCtr and NodEdge, along with markers related to hyaluronan turnover and hypoxia. Markers of brown adipocytic differentiation were frequently co-localized with markers of hypoxia. In NodCtr and NodSurr, brown fat and ossification markers correlated with hyaluronidase-1, whereas these markers, as well as hypoxia, correlated with hyaluronan synthases in NodEdge. The protein product of tumor necrosis factor-? stimulated gene-6 strongly correlated with ossification markers and hyaluronidase in the regions surrounding the nodules (NodSurr, PreNodSurr). In conclusion, this study suggests roles for hyaluronan homeostasis and the promotion of hypoxia by cells demonstrating brown fat markers in calcific aortic valve disease
In vivo testing of a bone graft containing chitosan, calcium sulfate and osteoblasts in a paste form in a critical size defect model in rats
P075 Comparative efficacy of bortezomib and carfilzomib desensitization protocols in highly sensitized cardiac transplant candidates
Effect of donor HSD17B13 genotype on patient survival after liver transplant: a retrospective cohort studyResearch in context
Summary: Background: Several genetic variants are associated with chronic liver disease. The role of these variants in outcomes after liver transplantation (LT) is uncertain. The aim of this study was to determine if donor genotype at risk-associated variants in PNPLA3 (rs738409 C>G, p.I148M) and HSD17B13 (rs72613567 T>TA; rs80182459, p.A192Lfs∗8) influences post-LT survival. Methods: In this retrospective cohort study, data on 2346 adults who underwent first-time LT between January 1, 1999 and June 30, 2020 and who had donor DNA samples available at five large Transplant Immunology Laboratories in Texas, USA, were obtained from the United Network for Organ Sharing (UNOS). Duplicates, patients with insufficient donor DNA for genotyping, those who were <18 years of age at the time of transplant, had had a previous transplant or had missing genotype data were excluded. The primary outcomes were patient and graft survival after LT. The association between donor genotype and post-LT survival was examined using Kaplan–Meier method and multivariable-adjusted Cox proportional hazards models. Findings: Median age of LT recipients was 57 [interquartile range (IQR), 50–62] years; 837 (35.7%) were women; 1362 (58.1%) White, 713 (30.4%) Hispanic, 182 (7.8%) Black/African-American. Median follow-up time was 3.95 years. Post-LT survival was not affected by donor PNPLA3 genotype but was significantly reduced among recipients of livers with two HSD17B13 loss-of-function (LoF) variants compared to those receiving livers with no HSD17B13 LoF alleles (unadjusted one-year survival: 82.6% vs 93.9%, P < 0.0001; five-year survival: 73.1% vs 82.9%, P = 0.0017; adjusted hazard ratio [HR], 2.25; 95% CI, 1.61–3.15 after adjustment for recipient age, sex, and self-reported ethnicity). Excess mortality was restricted to those receiving steroid induction immunosuppression (crude 90-day post-LT mortality, 9.3% [95% CI, 1.9%–16.1%] vs 1.9% [95% CI, 0.9%–2.9%] in recipients of livers with two vs no HSD17B13 LoF alleles, P = 0.0012; age, sex, and ethnicity-adjusted HR, 2.85; 95% CI, 1.72–4.71, P < 0.0001). No reduction was seen among patients who did not receive steroid induction (90-day mortality 3.1% [95% CI, 0%–7.3%] vs 2% [95% CI, 0.9%–3.1%], P = 0.65; adjusted HR, 1.17; 95% CI, 0.66–2.08, P = 0.60). Interpretation: Donor HSD17B13 genotype adversely affects post-LT survival in patients receiving steroid induction. Additional studies are required to confirm this association. Funding: The National Institutes of Health and American Society of Transplant Surgeons Collaborative Scientist Gran