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Crane, G.

Publications and source records attributed to Crane, G..

3 recordsLinked to original sources

Scalable Fabrication of a Tough and Recyclable Spore-Bearing Biocomposite Thermoplastic Polyurethane

Thermoplastic polyurethanes (TPUs) are a class of versatile thermoplastic elastomers where most of their products lack a proper recycling strategy or have no end-of-life solutions. To pursue a sustainable end-of-life solution for TPU based products, self-disintegrating biocomposite TPUs have recently been developed by embedding spores of TPU-degrading bacteria into TPUs using melt extrusion. Herein, we improve upon spore-bearing biocomposites and demonstrate industrially-relevant manufacturing conditions for the fabrication of biocomposite TPUs. Spore production was modified to reduce the innate brown color of the resulting materials and, effectively minimize the coloration of biocomposite TPUs. Reduction of FeSO4 in a sporulation media generated white spores without compromising spore productivity, viability, morphology or heat-shock tolerance. Biocomposite TPUs containing white spores displayed a 45% increase in toughness compared to TPUs without spores, while retaining [~]90% spore viability post processing. Furthermore, biocomposite TPU fabrication was demonstrated using a scalable continuous extruder followed by injection molding. Biocomposite TPUs generated by these industry-relevant processes exhibited comparable toughness improvement and spore viability to biocomposite TPU prepared using a lab scale microcompounder, while enhancing productivity by 30-fold. Finally, spore addition improved biocomposite TPUs recyclability, enabling 80% toughness retention after 5 rounds of iterative melt processing. Additionally, no negative effect on the lifespan of the generated TPUs was observed over a duration of 1 year of storage. Overall, this study confirmed that spore-bearing biocomposite TPUs are promising for practical applications, offering an accessible method to enhance toughness and sustainability of commercial TPUs through the incorporation of spore-based living fillers.

bioengineering↗

SINGLE CELL RESOLUTION SPATIAL MAPPING OF HUMAN HEMATOPOIESIS REVEALS AGING-ASSOCIATED TOPOGRAPHIC REMODELING

The spatial anatomy of hematopoiesis in bone marrow has been extensively studied in mice and other preclinical models, but technical challenges have precluded a commensurate exploration in humans. Institutional pathology archives contain thousands of paraffinized bone marrow core biopsy tissue specimens, providing a rich resource for studying the intact human bone marrow topography in a variety of physiologic states. Thus, we developed an end-to-end pipeline involving multiparameter whole tissue staining, in situ imaging at single-cell resolution, and artificial intelligence (AI)-based digital image analysis, and then applied it to a cohort of disease-free samples to survey alterations in the hematopoietic topography associated with aging. Our data indicate heterogeneity in marrow adipose tissue (MAT) content within each age group, and an inverse correlation between MAT content and proportions of early myeloid and erythroid precursors, irrespective of age. We identify consistent endosteal and perivascular positioning of hematopoietic stem and progenitor cells (HSPCs) with medullary localization of more differentiated elements and, importantly, uncover new evidence of aging-associated changes in cellular and vascular morphologies, microarchitectural alterations suggestive of inflammaging, and diminution of a potentially active megakaryocytic niche. Overall, our findings suggest that there is topographic remodeling of human hematopoiesis associated with aging. More generally, we demonstrate the potential to deeply unravel the spatial biology of normal and pathologic human bone marrow states using intact archival tissue specimens.

systems biology↗

Integrin alpha11 is an Osteolectin receptor and is required for the maintenance of adult skeletal bone mass

We previously discovered a new osteogenic growth factor that is required to maintain adult skeletal bone mass, Osteolectin/Clec11a. Osteolectin acts on Leptin Receptor+ (LepR+) skeletal stem cells and other osteogenic progenitors in bone marrow to promote their differentiation into osteoblasts. Here we identity a receptor for Osteolectin, 11 integrin, which is expressed by LepR+ cells and osteoblasts. 11{beta}1 integrin binds Osteolectin with nanomolar affinity and is required for the osteogenic response to Osteolectin. Deletion of Itga11 (which encodes 11) from mouse and human bone marrow stromal cells impaired osteogenic differentiation and blocked their response to Osteolectin. Like Osteolectin deficient mice, Lepr-cre; Itga11fl/fl mice appeared grossly normal but exhibited reduced osteogenesis and accelerated bone loss during aging. Osteolectin binding to 11{beta}1 promoted Wnt pathway activation, which was necessary for the osteogenic response to Osteolectin. This reveals a new mechanism for maintenance of adult bone mass: Wnt pathway activation by Osteolectin/11{beta}1 signaling.

developmental biology↗