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- All Subjects: Biomedical Engineering
Description
Sutures, staples, and tissue glues remain the primary means of tissue approximation and vessel ligation. Laser-activated tissue sealing is an alternative approach that conventionally employs light-absorbing chromophores and nanoparticles for converting near-infrared (NIR) laser to heat. The local increase in temperature engenders interdigitation of sealant and tissue biomolecules, resulting in rapid tissue sealing. Light-activated sealants (LASE) were developed in which indocyanine green (ICG) dye is embedded within a biopolymer matrix (silk or chitosan) for incisional defect repair. Light-activated tissue-integrating sutures (LATIS) that synergize the benefits of conventional suturing and laser sealing were also fabricated and demonstrated higher efficacies for tissue biomechanical recovery and repair in a full-thickness, dorsal surgical incision model in mice compared to commercial sutures and cyanoacrylate skin glue. Localized delivery of modulators of tissue repair, including histamine and copper, from LASE and LATIS further improved healed skin strength. In addition to incisional wounds, histamine co-delivered with silk fibroin LASE films accelerated the closure of full thickness, splinted excisional wounds in immunocompetent BALB/c mice and genetically obese and diabetic db/db mice, resulting in faster closure than Tegaderm wound dressing. Immunohistochemistry analyses showed LASE-histamine treatment enhanced wound repair involving mechanisms of neoangiogenesis, myofibroblast activation, transient epidermal EMT, and also improve healed skin biomechanical strength which are hallmarks of improved healing outcomes. Benefit of temporal delivery was further investigated of a second therapeutic (growth factor nanoparticles) in modulating wound healing outcomes in both acute and diabetic wounds. The hypothesis of temporal delivery of second therapeutic around the ‘transition period’ in wounds further improved wound closure kinetics and biomechanical recovery of skin strength. Laser sealing and approximation, together with delivery of immunomodulatory mediators, can lead to faster healing and tissue repair, thus reducing wound dehiscence, preventing wounds moving towards chronicity and lowering incidence of surgical site infections, all of which can have significant impact in the clinic.
ContributorsGhosh, Deepanjan (Author) / Rege, Kaushal (Thesis advisor) / Acharya, Abhinav (Committee member) / Holloway, Julianne (Committee member) / DiCaudo, David (Committee member) / P. Leung, Kai (Committee member) / Arizona State University (Publisher)
Created2021
Description
Tissues within the body enable proper function throughout an individual’s life. After severe injury or disease, many tissues do not fully heal without surgical intervention. The current surgical procedures aimed to repair tissues are not sufficient to fully restore functionality. To address these challenges, current research is seeking new tissue engineering approaches to promote tissue regeneration and functional recovery. Of particular interest, biomaterial scaffolds are designed to induce tissue regeneration by mimicking the biophysical and biochemical aspects of native tissue. While many scaffolds have been designed with homogenous properties, many tissues are heterogenous in nature. Thus, fabricating scaffolds that mimic these complex tissue properties is critical for inducing proper healing after injury. Within this dissertation, scaffolds were designed and fabricated to mimic the heterogenous properties of the following tissues: (1) the vocal fold, which is a complex 3D structure with spatially controlled mechanical properties; and (2) musculoskeletal tissue interfaces, which are fibrous tissues with highly organized gradients in structure and chemistry. A tri-layered hydrogel scaffold was fabricated through layer-by-layer stacking to mimic the mechanical structure of the vocal fold. Furthermore, magnetically-assisted electrospinning and thiol-norbornene photochemistry was used to fabricate fibrous scaffolds that mimic the structural and chemical organization of musculoskeletal interfacial tissues. The work presented in this dissertation further advances the tissue engineering field by using innovative techniques to design scaffolds that recapitulate the natural complexity of native tissues.
ContributorsTindell, Raymond Kevin (Author) / Holloway, Julianne (Thesis advisor) / Green, Matthew (Committee member) / Pizziconi, Vincent (Committee member) / Stephanopoulos, Nicholas (Committee member) / Acharya, Abhinav (Committee member) / Arizona State University (Publisher)
Created2021
Description
Annually, approximately 1.7 million people suffer a traumatic brain injury (TBI) in the United States. After initial insult, a TBI persists as a series of molecular and cellular events that lead to cognitive and motor deficits which have no treatment. In addition, the injured brain activates the regenerative niches of the adult brain presumably to reduce damage. The subventricular zone (SVZ) niche contains neural progenitor cells (NPCs) that generate astrocytes, oligodendrocyte, and neuroblasts. Following TBI, the injury microenvironment secretes signaling molecules like stromal cell derived factor-1a (SDF-1a). SDF-1a gradients from the injury contribute to the redirection of neuroblasts from the SVZ towards the lesion which may differentiate into neurons and integrate into existing circuitry. This repair mechanism is transient and does not lead to complete recovery of damaged tissue. Further, the mechanism by which SDF-1a gradients reach SVZ cells is not fully understood. To prolong NPC recruitment to the injured brain, exogenous SDF-1a delivery strategies have been employed. Increases in cell recruitment following stroke, spinal cord injury, and TBI have been demonstrated following SDF-1a delivery. Exogenous delivery of SDF-1a is limited by its 28-minute half-life and clearance from the injury microenvironment. Biomaterials-based delivery improves stability of molecules like SDF-1a and offer control of its release.
This dissertation investigates SDF-1a delivery strategies for neural regeneration in three ways: 1) elucidating the mechanisms of spatiotemporal SDF-1a signaling across the brain, 2) developing a tunable biomaterials system for SDF-1a delivery to the brain, 3) investigating SDF-1a delivery on SVZ-derived cell migration following TBI. Using in vitro, in vivo, and in silico analyses, autocrine/paracrine signaling was necessary to produce SDF-1a gradients in the brain. Native cell types engaged in autocrine/paracrine signaling. A microfluidics device generated injectable hyaluronic-based microgels that released SDF-1a peptide via enzymatic cleavage. Microgels (±SDF-1a peptide) were injected 7 days post-TBI in a mouse model and evaluated for NPC migration 7 days later using immunohistochemistry. Initial staining suggested complex presence of astrocytes, NPCs, and neuroblasts throughout the frontoparietal cortex.
Advancement of chemokine delivery was demonstrated by uncovering endogenous chemokine propagation in the brain, generating new approaches to maximize chemokine-based neural regeneration.
ContributorsHickey, Kassondra (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Holloway, Julianne (Committee member) / Caplan, Michael (Committee member) / Brafman, David (Committee member) / Newbern, Jason (Committee member) / Arizona State University (Publisher)
Created2021
Description
This work describes the development of a device for measuring CO2 in breath, which has applications in monitoring a variety of health issues, such as Chronic Obstructive Pulmonary Disease (COPD), asthma, and cardiovascular disease. The device takes advantage of colorimetric sensing technology in order to maintain a low cost and high user-friendliness. The sensor consists of a pH dye, reactive element, and base coated on a highly porous Teflon membrane. The transmittance of the sensor is measured in the device via a simple LED/photodiode system, along with the flow rate, ambient relative humidity, and barometric pressure. The flow is measured by a newly developed flow meter described in this work, the Confined Pitot Tube (CPT) flow meter, which provides a high accuracy with reduced flow-resistance with a standard differential pressure transducer. I demonstrate in this work that the system has a high sensitivity, high specificity, fast time-response, high reproducibility, and good stability. The sensor has a simple calibration method which requires no action by the user, and utilizes a sophisticated, yet lightweight, model in order to predict temperature changes on the sensor during breathing and track changes in water content. It is shown to be effective for measuring CO2 waveform parameters on a breath-by-breath basis, such as End-Tidal CO2, Alveolar Plateau Slope, and Beginning Exhalation Slope.
ContributorsBridgeman, Devon (Author) / Forzani, Erica S (Thesis advisor) / Nikkhah, Mehdi (Committee member) / Holloway, Julianne (Committee member) / Raupp, Gregory (Committee member) / Emady, Heather (Committee member) / Arizona State University (Publisher)
Created2017
Description
Combining 3D bio-printing and drug delivery are promising techniques tofabricate scaffolds with well controlled and patient-specific structures for tissue
engineering. In this study, silk derivatives of bioink were developed consisting of
silk fibroin and gelatin then 3D printed into scaffolds. The scaffolds would be
evaluated for small molecule release, cell growth, degradation, and morphology.
Preparations and design of the scaffolds are major parts of engineering and tissue
engineering. Scaffolds are designed to mimic extracellular matrix by providing
structural support as well as promoting cell attachment and proliferation with
minimum inflammation while degrading at a controlled rate. Scaffolds offers new
potentials in medicine by aiding in the preparation of personalized and controlled
release therapeutic systems.
ContributorsNg, Johnny (Author) / Rege, Kaushal (Thesis advisor) / Holloway, Julianne (Committee member) / Jin, Kailong (Committee member) / Arizona State University (Publisher)
Created2022
Description
Tissue approximation and repair have been performed with sutures and staples for centuries, but these means are inherently traumatic. Tissue repair using laser-responsive nanomaterials can lead to rapid tissue sealing and repair and is an attractive alternative to existing clinical methods. Laser tissue welding is a sutureless technique for sealing incised or wounded tissue, where chromophores convert laser light to heat to induce in tissue sealing. Introducing chromophores that absorb near-infrared light creates differential laser absorption and allows for laser wavelengths that minimizes tissue damage.
In this work, plasmonic nanocomposites have been synthesized and used in laser tissue welding for ruptured porcine intestine ex vivo and incised murine skin in vivo. These laser-responsive nanocomposites improved tissue strength and healing, respectively. Additionally, a spatiotemporal model has been developed for laser tissue welding of porcine and mouse cadaver intestine sections using near-infrared laser irradiation. This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser welding. Finally, in a model of surgical site infection, laser-responsive nanomaterials were shown to be efficacious in inhibiting bacterial growth. By incorporating an anti-microbial functionality to laser-responsive nanocomposites, these materials will serve as a treatment modality in sealing tissue, healing tissue, and protecting tissue in surgery.
In this work, plasmonic nanocomposites have been synthesized and used in laser tissue welding for ruptured porcine intestine ex vivo and incised murine skin in vivo. These laser-responsive nanocomposites improved tissue strength and healing, respectively. Additionally, a spatiotemporal model has been developed for laser tissue welding of porcine and mouse cadaver intestine sections using near-infrared laser irradiation. This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser welding. Finally, in a model of surgical site infection, laser-responsive nanomaterials were shown to be efficacious in inhibiting bacterial growth. By incorporating an anti-microbial functionality to laser-responsive nanocomposites, these materials will serve as a treatment modality in sealing tissue, healing tissue, and protecting tissue in surgery.
ContributorsUrie, Russell Ricks (Author) / Rege, Kaushal (Thesis advisor) / Acharya, Abhinav (Committee member) / DeNardo, Dale (Committee member) / Holloway, Julianne (Committee member) / Thomas, Marylaura (Committee member) / Arizona State University (Publisher)
Created2019