Biology subjects

Sprott, M.

Publications and source records attributed to Sprott, M..

3 recordsLinked to original sources

bioRxiv2025

Bioengineered bone marrows that can support stem cells and remodel to mimic human disease metabolism and chemotherapeutic effects

Blood cancer drug discovery is reliant on poorly predictive and costly animal models. Therefore, bioengineered, human cell containing, models are attractive to Pharma. Designing effective bone marrow (BM) models is complicated as they need to both regulate haematopoietic stem cell (HSC) phenotype and be able to undergo remodelling to mimic the blood cancer microenvironment. Here, we develop synthetic hybrid niches using poly(ethylacrylate) to organise laminin on hard, bone mimicking, surfaces and interface with soft, marrow mimicking, polyethylene glycol-fibronectin hydrogels. Optimisation of mesenchymal stromal cell (MSC) mechanobiology within the model offers both support for HSCs and remodelling in response to acute myeloid leukaemia derived cells. The remodelling has many parallels to in vivo and patient data including increased dependency on nestin+ve MSCs, enhanced cytoprotection and increased taurine metabolism. We also use the model to demonstrate, as has been seen in vivo, that targeting taurine enhances effects of chemotherapy.

bioengineering↗

bioRxiv2024

Developing and Investigating a Nanovibration Intervention for the Prevention/Reversal of Bone Loss Following Spinal Cord Injury

Osteoporosis disrupts the fine-tuned balance between bone formation and resorption leading to reductions in bone quantity and quality, ultimately leading to increased fracture risk. Prevention and treatment of osteoporotic fractures is essential, for reductions in mortality, morbidity and the economic burden, particularly considering the ageing global population. Extreme bone loss that mimics time-accelerated osteoporosis develops in the paralysed limbs following complete spinal cord injury (SCI). In vitro nanoscale vibration (1 kHz, 30- or 90 nm amplitude) has been shown to drive differentiation of mesenchymal stem cells towards osteoblast-like phenotypes, enhancing osteogenesis, and inhibiting osteoclastogenesis, simultaneously. Here we develop and characterise a wearable device designed to deliver continuous nano-amplitude vibration to the hindlimb long bones of rats with complete SCI. We investigate whether a clinically feasible dose of nanovibration (4-hours/day, 5-days/week for 6 weeks) is effective at reversing the established SCI-induced osteoporosis. Laser interferometry and finite element analysis confirmed transmission of nanovibration into the bone, and micro-computed tomography and serum bone formation and resorption markers assessed effectiveness. The intervention did not reverse SCI-induced osteoporosis. However, serum analysis indicated an elevated concentration of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) in rats receiving 40 nm amplitude nanovibration, suggesting increased synthesis of type 1 collagen, the major organic component of bone. Therefore, enhanced doses of nanovibrational stimulus may yet prove beneficial in attenuating/reversing osteoporosis, particularly in less severe forms of osteoporosis.

bioengineering↗

bioRxiv2020

PEA polymer-coated nanotopography delivers solid-state BMP2, enhances mesenchymal stem cell adhesion, prevents bacterial biofilm formation and protects cells from quorum sensing virulence factors

Post-operative infection is a major complication in patients recovering from orthopaedic surgery. As such, there is a clinical need to develop biomaterials for use in regenerative surgery that can promote mesenchymal stem cell (MSC) osteospecific differentiation and that can prevent infection caused by biofilm-forming pathogens. Nanotopographical approaches to pathogen control are being identified, including in orthopaedic materials such as titanium and its alloys. These topographies use high aspect ratio nanospikes or nanowires to prevent bacterial adhesion but these features puncture adhering cells, thus also reducing MSC adhesion. Here, we use a poly(ethyl acrylate) (PEA) polymer coating on titanium nanowires to spontaneously organise fibronectin (FN) and to deliver bone morphogenetic protein 2 (BMP2) to enhance MSC adhesion and osteospecific signalling. This nanotopography when combined with the PEA coating enhanced osteogenesis and reduced adhesion of Pseudomonas aeruginosa in culture. Using a novel MSC-Pseudomonas aeruginosa co-culture, we also show that the coated nanotopographies protect MSCs from cytotoxic quorum sensing and signalling molecules. We conclude that the PEA polymer-coated nanotopography can both support MSCs and prevent pathogens from adhering to a biomaterial surface, thus protecting from biofilm formation and bacterial infection and supporting osteogenic repair.

bioengineering↗