Biology subjects

Shah, F. A.

Publications and source records attributed to Shah, F. A..

3 recordsLinked to original sources

bioRxiv2024

Pyrophosphate-containing Calcium Phosphates Negatively Impact Heterotopic Bone Quality

In bone, critical size defects pose substantial challenge in maxillofacial and orthopaedic reconstructions as they are incapable of spontaneous regeneration. Autologous bone grafts remain the "gold standard" in bone repair but their limitations and associated morbidities drive the development of bone graft substitute materials. Assessing the osteoinductive properties of these substitutes can help predict their success in bone regeneration applications. Calcium phosphates (CaP) are widely used bone graft substitutes due to their biocompatibility, osteoconductive properties, and potential for osteoinductivity. CaP materials containing monetite, beta-tricalcium phosphate ({beta}-TCP), and a small amount of calcium pyrophosphate (Ca-PP) possess both osteoconductive and osteoinductive properties. However, the role of Ca-PP in osteoinduction and material degradation remains unexplored. This study investigates heterotopic bone formation in response to five CaP material compositions, maintaining a constant monetite and {beta}-TCP ratio, with varying amounts of Ca-PP (0 - 12.5%). Twelve adult female sheep (Ovis aries) were subcutaneously implanted with constructs made of six CaP tiles interconnected by a Ti6Al4V frame and a control implant. Histological analysis, backscattered electron scanning electron microscopy, and Raman spectroscopy of samples retrieved at 12- and 52 weeks reveal that Ca-PP does not hinder heterotopic bone formation and minimally impacts CaP degradation. While monetite and {beta}-TCP transform into apatite, the Ca-PP phase remains unchanged. The addition of Ca-PP to the CaP material influences heterotopic bone quality and inflammatory response during tissue regeneration.

bioengineering↗

bioRxiv2023

Shedding light (... electrons) on human bone ultrastructure with correlative on-axis electron tomography and energy dispersive X-ray spectroscopy tomography

Mineralized collagen fibrils are the building block units of bone at the nanoscale. While it is known that collagen fibrils are mineralized both inside their gap zones (intra-fibrillar mineralization) and on their outer surfaces (extra-fibrillar mineralization), a clear visualization of this architecture in three dimensions (3D), combining structural and compositional information over large volumes, but without compromising the resolution, remains challenging. In this study, we demonstrate the use of on-axis Z-contrast electron tomography (ET) with correlative energy-dispersive X-ray spectroscopy (EDX) tomography to examine rod-shaped samples with a diameter up to 700 nm prepared from individual osteonal lamellae in the human femur. Our work mainly focuses on two aspects: i) low-contrast nanosized circular spaces ("holes") observed in sections of bone oriented perpendicular to the long axis of a long bone; and ii) extra-fibrillar mineral, especially in terms of morphology and spatial relationship with respect to intra-fibrillar mineral and collagen fibrils. From our analyses, it emerges quite clearly that most "holes" are cross-sectional views of collagen fibrils. While this had been postulated before, our 3D reconstructions and reslicing along meaningful two-dimensional (2D) cross-sections provide a direct visual confirmation. Extra-fibrillar mineral appears composed of thin plates that are interconnected and span over several collagen fibrils, confirming that mineralization is cross-fibrillar, at least for the extra-fibrillar phase. EDX tomography shows mineral signature (Ca and P) within the gap zones, but the signal appears weaker than that associated to the extra-fibrillar mineral, pointing towards the existence of dissimilarities between the two types of mineralization.

bioengineering↗

bioRxiv2020

Revisiting the Association between Human Leukocyte Antigen and End-Stage Renal Disease

Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD) showing, however, contradictory and inconsistent results. Here, we revisit the association between ESRD and HLA antigens, comparing HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n=497) and controls (n=672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also determined whether heterozygosity or homozygosity of the ESRD-associated HLA alleles at different loci could modify the prevalence of the disease. Few HLA allele combinations displayed significant associations with ESRD among which HLA-A*3-HLA-A*26 combination showed the highest strength of association (OR= 4.488, P[≤] 0.05) with ESRD. Interestingly, the age of ESRD onset was not affected by HLA allele combinations at different loci. We also performed an extensive literature analysis to determine whether the association of HLA to ESRD can be similar across different ethnic groups. Our analysis showed at least for certain alleles, HLA-A*11, HLA-DRB1*11, and HLA-DRB1*4, a significant association of HLA to ESRD in different ethnic groups. The findings of our study will help in determining possible protective or susceptible roles of various HLA alleles in ESRD.

molecular biology↗