Biomaterials Commons^™

Novel Approaches For Enhancing Cell Survival And Function In Vivo, Ou Wang

Department of Chemical and Biomolecular Engineering: Theses and Student Research

FDA has approved several cell-based therapeutics and hundreds of cell therapy clinical trials are ongoing. Cells will be a significant type of medicine after small molecule and protein drugs. However, several obstacles need to be addressed to achieve the widespread use of cellular therapeutics. The first challenge is the low efficacy of cell transplantation due to low retention, survival, integration, and function of cells in vivo. The second challenge is producing a massive number of cells for clinical treatment with cost-effectively and reproducibly technologies.

In this thesis, we proposed and investigated two approaches to address these challenges. To begin …

A Single Cell Pair Mechanical Interrogation Platform To Study Cell-Cell Adhesion Mechanics, Amir Monemianesfahani

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Cell-cell adhesion complexes are macromolecular adhesive organelles that integrate cells into tissues. Perturbations of the cell-cell adhesion structure or relatedmechanotransduction pathways lead to pathological conditions such as skin and heart diseases, arthritis, and cancer. Mechanical stretching has been used to stimulate the mechanotransduction process originating from the cell-cell adhesion and cell-extracellular matrix (ECM) complexes. The current techniques, however, have limitations on their ability to measure the cell-cell adhesion force directly and quantitatively. These methods use a monolayer of cells, which makes it impossible to quantify the forces within a single cell-cell adhesion complex. Other methods using single cells or cell …

Impact Of Angiogenic And Osteogenic Factors In The Presence Of Biodegradable Piezoelectric Films, Jayla Millender

University Scholar Projects

One of the most common causes of bone graft rejection is lack of a vascular network connecting the graft to the existing native tissue – allowing for nutrient flow. Under current grafting techniques, the existing blood vessel network in the patient slowly invades the implant in order to supply the injured site with its necessary nutrients. The purpose of this research is to determine if a synthetic bone graft with a stable microvascular network can be developed in vitro. I hypothesize that the use of indirect angiogenic factors such as sonic hedgehog homolog and hypoxia-inducible factor-1 in combination with the …

Impact Of Angiogenic And Osteogenic Factors In The Presence Of Biodegradable Piezoelectric Films, Jayla Millender

Honors Scholar Theses

One of the most common causes of bone graft rejection is lack of a vascular network connecting the graft to the existing native tissue – allowing for nutrient flow. Under current grafting techniques, the existing blood vessel network in the patient slowly invades the implant in order to supply the injured site with its necessary nutrients. The purpose of this research is to determine if a synthetic bone graft with a stable microvascular network can be developed in vitro. I hypothesize that the use of indirect angiogenic factors such as sonic hedgehog homolog and hypoxia-inducible factor-1 in combination with the …

Hydrolytic Degradation Study Of Polyphosphazene-Plga Blends, Riley Blumenfield

Honors Scholar Theses

The synthesis and in vitro degradation analysis of thin films of poly[(glycineethylglycinato)₇₅(phenylphenoxy)₂₅phosphazene]
(PNGEG₇₅PhPh₂₅) and poly[(ethylphenylalanato)₂₅(glycine-
ethylglycinato)₇₅phosphazene] (PNEPA₂₅GEG₇₅) blended with poly(lactic-co-glycolic acid) (PLGA) was conducted to determine the blends’ potential for use as scaffolding materials for tissue regeneration applications. The samples were synthesized with glycylglycine ethyl ester (GEG) acting as the primary substituent side group, with cosubstitution by phenylphenol (PhPh) and phenylalanine ethyl ester (EPA) to make the final product [1]. Blends of 25% polyphosphazene, 75% PLGA and 50% polyphosphazene, 50% PLGA were …

Bubble Lab Exercise, Peter Beltramo

Science and Engineering Saturday Seminars

The cell membrane is a ubiquitous component in mammalian cells which control many vital biological functions. It consists of a phospholipid bilayer with embedded protein molecules which serve to transport molecules between the interior and exterior of the cell. Understanding what makes cell membranes so important and how they function requires concepts from physics, chemistry, and of course biology, but it is difficult to learn and conceptualize the structure and function of membranes due to their nanoscopic size and dynamic nature which can’t be properly appreciated in a static textbook. This activity draws analogies between the chemistry and structure of …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …

Developing Vascular Graft From Adipose-Derived Stem Cells, Ashley C. Apil

Research Opportunities for Engineering Undergraduates (ROEU) Program 2017-18

This project aims to differentiate adipose-derived stem cells into fibroblasts through the addition of platelet-derived growth factor (PDGF) into the culture media. Differentiation protocol will be optimized, then successful differentiation will be verified through PCR analysis. The ASC-fibroblasts will then be seeded into a ring construct as outlined by the protocol by Lam et al. The ring constructs will be tensile tested and analyzed through histology to characterize their strength and cellularity.

A Tunable, Three-Dimensional In Vitro Culture Model Of Growth Plate Cartilage Using Alginate Hydrogel Scaffolds, Alek G. Erickson, Taylor D. Laughlin, Sarah Romereim, Catherine Sargus-Patino, Angela K. Pannier, Andrew T. Dudley

Biological Systems Engineering: Papers and Publications

Defining the final size and geometry of engineered tissues through precise control of the scalar and vector components of tissue growth is a necessary benchmark for regenerative medicine, but it has proved to be a significant challenge for tissue engineers. The growth plate cartilage that promotes elongation of the long bones is a good model system for studying morphogenetic mechanisms because cartilage is composed of a single cell type, the chondrocyte; chondrocytes are readily maintained in culture; and growth trajectory is predominately in a single vector. In this cartilage, growth is generated via a differentiation program that is spatially and …

Ultrasonically Responsive Tissue Engineering Scaffolds For The Temporal Control Over Osteo-Inductive Growth Factor Delivery, Catherine Linh

Senior Honors Projects

In 2012, approximately 6.8 million people in the United States were diagnosed with orthopedic injuries or diseases. Over 500,000 people in the United States underwent bone grafting procedures, which cost 2.5 billion dollars per year and can result in complications. Polymer-based grafting scaffolds can facilitate 3D bone tissue growth in a localized, sustained manner. However, bone regeneration requires the orchestration of a sequence of events. Current scaffolds based on degradation and diffusion cannot provide sequential deliveries. We aimed to design a polymer scaffold that can release one payload diffusively at early time points, followed by ultrasonically triggered release of a …

Chitosan Nanoparticle Modifications For Improved Gene Delivery In An Oral Dna Vaccine Application, Austin Helmink

Honors Theses

Vaccines represent one of the most significant medical innovations of the 20^th century, resulting in the eradication or near eradication of a handful of deadly diseases. However, many infectious diseases remain resistant to effective vaccination, largely due to a lack full immune activation by traditional protein-based vaccines. A promising alternative vaccination strategy is the emerging development of DNA vaccines, which rely upon the delivery of exogenous genetic material to host cells encoding for a viral or bacterial antigen in order to induce a robust immune response by closely mimicking live infection. The delivery of genetic material requires a carrier …

The Effect Of Hyperthermia On Doxorubicin Therapy And Nanoparticle Penetration In Multicellular Ovarian Cancer Spheroids, Abhignyan Nagesetti

FIU Electronic Theses and Dissertations

The efficient treatment of cancer with chemotherapy is challenged by the limited penetration of drugs into the tumor. Nanoparticles (10 – 100 nanometers) have emerged as a logical choice to specifically deliver chemotherapeutics to tumors, however, their transport into the tumor is also impeded owing to their bigger size compared to free drug moieties. Currently, monolayer cell cultures, as models for drug testing, cannot recapitulate the structural and functional complexity of in-vivo tumors. Furthermore, strategies to improve drug distribution in tumor tissues are also required. In this study, we hypothesized that hyperthermia (43°C) will improve the distribution of silica nanoparticles …

The Effect Of Tgfβ-1 On Adipose-Derived Stem Cell (Asc) Ring Constructs, Ashley C. Apil

Research Opportunities for Engineering Undergraduates (ROEU) Program 2016-17

Adipose-derived Stem Cells (ASC’s) provide an optimal source for potentially graft replacing, tissue-engineered vessel constructs due to their ease of extraction and ability to be patient-specific. In order to make ASC ring constructs a more viable replacement for grafts, they need to have mechanical properties similar to native arteries, which is largely influenced by the extracellular matrix protein collagen. TGFβ-1 is known to stimulate collagen production in ASC’s, so this study explores the effect that TGFβ-1 has on the resulting thickness and tensile strength of ASC ring constructs.

Characterization Of Molecular Communication Based On Cell Metabolism Through Mutual Information And Flux Balance Analysis, Zahmeeth Sayed Sakkaff

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

Synthetic biology is providing novel tools to engineer cells and access the basis of their molecular information processing, including their communication channels based on chemical reactions and molecule exchange. Molecular communication is a discipline in communication engineering that studies these types of communications and ways to exploit them for novel purposes, such as the development of ubiquitous and heterogeneous communication networks to interconnect biological cells with nano and biotechnology-enabled devices, i.e., the Internet of Bio-Nano Things. One major problem in realizing these goals stands in the development of reliable techniques to control the engineered cells and their behavior from the …

Alginate Hydrogels As Three-Dimensional Scaffolds For In Vitro Culture Models Of Growth Plate Cartilage Development And Porcine Embryo Elongation, Taylor D. Laughlin

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

The establishment of in vitro culture models utilizes tissue engineering principles to design functional mimics of in vivo environments in vitro. Advantages for the use of in vitro culture models include ethical alleviation of animal models for therapeutic testing, cost efficiency, and a greater ability to study specific mechanisms via a systematic, ground-up approach to development. In this thesis, alginate hydrogels are utilized in the development of in vitro culture models of porcine embryo elongation and growth plate cartilage development. First, the effect of scaffold and modifications to the scaffold were explored in both projects. In order to modulate …

Interaction Of Fibrinogen With Fibronectin: Purification And Characterization Of A Room Temperature-Stable Fibrinogen-Fibronectin Complex From Normal Human Plasma, Ayman E. Ismail

Department of Chemical and Biomolecular Engineering: Theses and Student Research

A fibrinogen-fibronectin complex (γγ’pdFI-pdFN) was purified from normal human plasma using a sequence of cryoprecipitation, ammonium sulfate fractionation, and DEAE Sepharose chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing condition showed both a 1:1 stoichiometric ratio of fibrinogen (FI) to fibronectin (FN) as well as a stoichiometric ratio of 1:1 of γg to gγ’. The γγ’pdFI-pdFN complex was non-covalent in nature as it was disrupted by affinity adsorption to Gelatin Sepharose where pdFN bound strongly and the disrupted γγ’pdFI fell through the chromatographic column. Surprisingly, the purified γγ’pdFI-pdFN complex was more broadly thermally stable than plasma FI (pdFI) …

Patterned Alginate Hydrogels To Induce Chondrocyte Alignment, Jordan Catherine Verplank, Taylor D. Laughlin, Angela K. Pannier

UCARE Research Products

The growth plate has an intricate architecture, and this architecture is necessary for directional growth of bones. Specifically, the cells align in longitudinal columns. As the growth plate expands with this pattern, the bone elongates with the same alignment pattern. The purpose of this research is to mimic this single celled, columnar alignment in vitro. In developing this alignment in vitro, this research will contribute to the overall study of growing growth for the development of improved therapeutic treatments and engineered tissues for transplants.

A Scalable Low-Cost Cgmp Process For Clinical Grade Production Of The Hiv Inhibitor 5p12-Rantes In Pichia Pastoris, Fabrice Cerini, Hubert Gaertner, Knut Madden, Ilya Tolstorukov, Scott Brown, Bram Laukens, Nico Callewaert, Jay C. Harner, Anna M. Oommen, John T. Harms, Anthony R. Sump, Robert C. Sealock, Dustin J. Peterson, Scott K. Johnson, Stephan B. Abramson, Michael M. Meagher, Robin Offord, Oliver Hartley

Department of Chemical and Biomolecular Engineering: Faculty Publications

In the continued absence of an effective anti-HIV vaccine, approximately 2 million new HIV infections occur every year, with over 95% of these in developing countries. Calls have been made for the development of anti-HIV drugs that can be formulated for topical use to prevent HIV transmission during sexual intercourse. Because these drugs are principally destined for use in low-resource regions, achieving production costs that are as low as possible is an absolute requirement. 5P12-RANTES, an analog of the human chemokine protein RANTES/CCL5, is a highly potent HIV entry inhibitor which acts by achieving potent blockade of the principal HIV …

A Collagen Based Tissue Engineered Heart Valve Shows Excellent Functionality And Remodelling After Dynamic Conditioning, Claire Brougham, Ricardo Moreira, Tanya J. Levingstone, Stefan Jockenhoevel, Petra Mela, Fergal J. O'Brien

Conference Papers

No abstract provided.

Incorporation Of Fibrin Into A Collagen–Glycosaminoglycan Matrix Results In A Scaffold With Improved Mechanical Properties And Enhanced Capacity To Resist Cell-Mediated Contraction, Claire Brougham, Tanya J. Levingstone, Stefan Jockenhoevel, Thomas C. Flanagan, Fergal J. O'Brien

Articles

Fibrin has many uses as a tissue engineering scaffold, however many in vivo studies have shown a reduction in function resulting from the susceptibility of fibrin to cell-mediated contraction. The overall aim of the present study was to develop and characterise a reinforced natural scaffold using fibrin, collagen and glycosaminoglycan (FCG), and to examine the cell-mediated contraction of this scaffold in comparison to fibrin gels. Through the use of an injection loading technique, a homogenous FCG scaffold was developed. Mechanical testing showed a sixfold increase in compressive modulus and a thirtyfold increase in tensile modulus of fibrin when reinforced with …

Breast Cancer/Stromal Cells Coculture On Polyelectrolyte Films Emulates Tumor Stages And Mirna Profiles Of Clinical Samples, Amita Daverey, Karleen M. Brown, Srivatsan Kidambi

Department of Chemical and Biomolecular Engineering: Faculty Publications

In this study, we demonstrate a method for controlling breast cancer cells adhesion on polyelectrolyte multilayer (PEM) films without the aid of adhesive proteins/ ligands to study the role of tumor and stromal cell interaction on cancer biology. Numerous studies have explored engineering coculture of tumor and stromal cells predominantly using transwell coculture of stromal cells cultured onto coverslips that were subsequently added to tumor cell cultures. However, these systems imposed an artificial boundary that precluded cell−cell interactions. To our knowledge, this is the first demonstration of patterned coculture of tumor cells and stromal cells that captures the temporal changes …

Design And Development Of Two Component Hydrogel Ejector For Three-Dimensional Cell Growth, Thomas Dunkle, Jessica Deschamps, Connie Dam

Honors Scholar Theses

Hydrogels are useful in wound healing, drug delivery, and tissue engineering applications, but the available methods of injecting them quickly and noninvasively are limited. The medical industry does not yet have access to an all-purpose device that can quickly synthesize hydrogels of different shapes and sizes. Many synthesis procedures that have been developed result in the formation of amorphous hydrogels. While generally useful, amorphous hydrogels exhibit limited capability in tissue engineering applications, especially due to their viscous properties. This endeavor aims to modulate the appropriate gelation parameters, optimize the injection process, and create a prototype that allows for the extrusion …

Finite Element Analysis Of The Application Of Ultrasound-Generated Acoustic Radiation Force To Biomaterials, Nicole J. Piscopo

Honors Scholar Theses

While most bone fractures can heal simply by being stabilized, others can take a longer time to rejoin or they could fail to merge back together completely. Numerous studies have shown the positive effects that ultrasonic therapy have had on delayed-union and non-union bone fracture repair but little is known as to what specific biological mechanisms are at play. Ultrasound may be a valuable tool for bone tissue regeneration at these fracture sites using a tissue engineering approach, however, more must be understood about its impact on stimulating tissues to heal before this can be a reality. For that reason, …

Fiber Scaffolds Of Poly (Glycerol-Dodecanedioate) And Its Derivative Via Electrospinning For Neural Tissue Engineering, Xizi Dai

FIU Electronic Theses and Dissertations

Peripheral nerves have demonstrated the ability to bridge gaps of up to 6 mm. Peripheral Nerve System injury sites beyond this range need autograft or allograft surgery. Central Nerve System cells do not allow spontaneous regeneration due to the intrinsic environmental inhibition. Although stem cell therapy seems to be a promising approach towards nerve repair, it is essential to use the distinct three-dimensional architecture of a cell scaffold with proper biomolecule embedding in order to ensure that the local environment can be controlled well enough for growth and survival. Many approaches have been developed for the fabrication of 3D scaffolds, …

Low Molecular Weight Glucosamine/L-Lactide Copolymers As Potential Carriers For The Development Of A Sustained Rifampicin Release System: Mycobacterium Smegmatis As A Tuberculosis Model, Jorge Ragusa

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged …

Investigation Of Membrane Mechanics Using Spring Networks: Application To Red-Blood-Cell Modelling, Mingzhu Chen, Fergal Boyle

Articles

In recent years a number of red-blood-cell (RBC) models have been proposed using spring networks to represent the RBC membrane. Some results predicted by these models agree well with experimental measurements. How- ever, the suitability of these membrane models has been questioned. The RBC membrane, like a continuum mem- brane, is mechanically isotropic throughout its surface, but the mechanical properties of a spring network vary on the network surface and change with deformation. In this work spring-network mechanics are investigated in large deformation for the first time via an assessment of the effect of network parameters, i.e. network mesh, spring …

Application Of Limited Mixing In The Hele-Shaw Geometry In Fabrication Of Janus Hydrogels, Md Mahmudur Rahman

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

It is widely accepted that cells behave differently responding to the stiffness of their extracellular matrix (ECM). Such observations were made by culturing cells on hydrogel substrates of tunable stiffness. However, it was recently proposed that cells may sense how strongly they are tethered to ECM, not the local stiffness of ECM. To investigate both hypotheses, we developed a method to fabricate Janus polyacrylamide (PAAM) gels. We squeeze two drops of different concentrations in the Hele-Shaw geometry to generate radial Stokes flow. When the drops coalesce, limited mixing occurs at the interface due to the narrow confinement, and diffusion normal …

Utilizing Fast Spin Echo Mri To Reduce Image Artifacts And Improve Implant/Tissue Interface Detection In Refractory Parkinson’S Patients With Deep Brain Stimulators, Subhendra N. Sarkar, Pooja R. Sarkar, Efstathios Papavassiliou, Rafael Rojas

Publications and Research

Introduction. In medically refractory Parkinson’s disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detectDBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity.

Methods. Using an IRB approved protocol 8 advanced PDpatientswere imagedwithinMRconditional safety guidelines at lowRF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences.The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads.

Results …