BME Summer Seminar Series

Wednesday, July 13^th, 2022

9:30-10:30AM EST

Via Zoom Meeting – link below*

Evaluation links:

Claudia Benito Alston: https://purdue.ca1.qualtrics.com/jfe/form/SV_eIPB8qSBTdiwCbA

Lexi Petrucciani: https://purdue.ca1.qualtrics.com/jfe/form/SV_2hhdmdxcdnMQcpE

Fully resorbable 3D printed bone graft for alveolar ridge reconstruction 

Claudia Benito Alston (L. Solorio, advisor)

Abstract: Oral and maxillofacial reconstruction, which is performed on 1.5 million patients worldwide each year, is required for a variety of intraoral and extraoral critically sized bone defects. These defects can originate from accidental injuries such as a car accident, congenital conditions such as cleft palate or diseases such as osteosarcoma which cause maxillofacial malignancies. We aim to generate a 3D printed patient-specific bone graft with controlled release of growth factors. The current standard of care uses particulates of freeze-dried auto- or allografts covered by a titanium mesh, which is then secured in place by screws. This approach is limited by its variability, the length of time the patient is exposed to potential infection during surgery, and although the highly packed allograft signals cells to differentiate along the osteogenic lineage, tight packing often leads to diminished as well as slow bone healing as blood vessels may fail to form. A significant benefit of the current gold-standard of freeze-dried particulate bone allografts are the growth factors (GFs) that are released by the particulates. However, since these are patient derived the GF composition is poorly defined and varies from patient to patient. To address these fallbacks, a 3D printable, biodegradable and implantable device with patient-specific shape and a porous core-cover structure was designed. The cover is porous for cell infiltration and will be loaded with GF releasing microspheres which aim to provide a means for spatial-temporal control of osteoinductive GFs. We hypothesize that the controlled release of microspheres containing growth factors BMP-2 and VEGF as well as FGF encapsulated microbubbles will increase the rate of osteoinduction of a 3D-printed graft. Overall, through a combination of finite element analysis modeling, as well as in vitro and in vivo studies, we aim to generate a patient specific bone graft with an increased rate of osteointegration.

Comparing Spheroid And Traditional Cultures Of M. Tuberculosis Using Agent-based Modeling

Lexi Petrucciani (E. Pienaar, advisor)

Abstract: Tuberculosis (TB) continues to be global public health crisis. In 2020, an estimated 1.3 million people died from TB. In vitro methods are commonly used to study host-pathogen interactions in M. tuberculosis (Mtb) infection. There has been a recent interest in developing spheroid models that can represent the TB granuloma environment more closely than the traditional cell culture plate counterparts. Previous work has shown that spheroid models using PBMCs have better bacterial control than traditional culture equivalents, but the cause of these differences is unclear. 

We use an in silico model to simulate both spheroid and traditional culture to explore whether the difference in Mtb control can be solely due to spatiality. An agent-based model is constructed with Mtb, macrophages (Mφ), CD4+ and CD8+ T cells. Mechanisms include phagocytosis of Mtb by Mφ and activation of Mφ through NFκB and STAT1. Parameters include secretion rates, activation thresholds, and probabilities of killing and movement. After a large parameter sweep using latin hypercube sampling, we select parameter sets that fell within the experimental Mtb counts and sampled ranges around these to enrich sets that represent the entire experimental range. 

Our results suggest that spatial differences alone can account for the differential Mtb control. Preliminary results suggest that poorer Mtb control in the traditional model is due to lower levels of Mφ activation. The difference in infected Mφ activation is specifically due to STAT1, implying more T cell activation in the spheroid model. But the opposite was seen, with traditional model having more activated T cells. 

Together, our results suggest that the spatial organization of spheroids allows for more targeted, effective T cell activation. Our model can be used to answer further hypotheses about the dynamics of early Mtb infection in granulomas and to possibly “3-dimensionalize” the results of traditional in vitro models. 

*Join Zoom Meeting

https://purdue-edu.zoom.us/j/92168739019?pwd=cnBOaFBxN3FWVVVTWC8wWWhaekdIdz09

Meeting ID: 921 6873 9019

Passcode: biomedical

Liz Rowen

She/Her

Graduate Program Assistant
Weldon School of Biomedical Engineering

Martin C. Jischke Hall of Biomedical Engineering
206 S. Martin Jischke Drive
West Lafayette, IN 47907-2032

o: 765-494-1197