Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551014
Pertenecen a esta colección Tesis y Trabajos de grado de los Doctorados correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- La sobrecarga de Ca2+ mitocondrial es un factor clave para el desarrollo de arritmias ventriculares mortales(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-12-05) Salazar Ramírez, Felipe de Jesús; García Rivas, Gerardo de Jesús; emimmayorquin; Rojas Martínez, Augusto; Altamirano Barrera, Julio; Zazueta Mendizábal, Ana Cecilia; Escuela de Medicina y Ciencias de la Salud; Campus MonterreyLas arritmias ventriculares son una causa principal de muerte en pacientes con enfermedades cardiovasculares y éstas se asocian a niveles elevados de catecolaminas. El transporte de Ca²⁺ mitocondrial es esencial para iniciar una respuesta adrenérgica; no obstante, la estimulación continua podría llevar a una sobrecarga de Ca²⁺ mitocondrial y disfunción mitocondrial dentro del tejido cardiaco. Este estudio se centra en investigar el rol del Ca²⁺ mitocondrial en arritmias letales y los efectos de su modulación. Ratones C57BL/6 machos fueron administrados con Ru360, un potente y selectivo inhibidor del transporte de Ca²⁺ mitocondrial, o con solución salina por vía intravenosa. Un electrocardiograma (ECG) basal fue tomado, seguido de una administración subcutánea de isoproterenol (ISO). El ECG fue monitoreado por 20 minutos más, después de los cuales se aislaron cardiomiocitos y mitocondrias para estudios de caracterización. La administración de ISO llevó al desarrollo de taquicardia y fibrilación ventriculares, pero el pretratamiento con Ru360 previno exitosamente estas arritmias. Las mitocondrias de corazones tratados con ISO mostraron un contenido de Ca²⁺ mayor, indicando sobrecarga, el cual comprometía la función mitocondrial y la integridad de membrana, evidenciado por un control respiratorio disminuido, menor capacidad de retención de Ca²⁺ y menor potencial de membrana. El ISO también incrementó el estrés oxidante, demostrado por una elevada producción de peróxido de hidrógeno, fuga de electrones y modificaciones oxidativas agudas, así como una dinámica de Ca²⁺ celular errática. Esta disfunción mitocondrial se correlacionó con una menor actividad de respirosomas, pero no a una diferencia en abundancia cuantificada por el perfilado complexómico, la cual fue prevenida por el pretratamiento con Ru360. La sobrecarga de Ca²⁺ mitocondrial contribuye significativamente al desarrollo de arritmias al perturbar la función de los respirosomas e incrementando el estrés oxidante, alterando la dinámica de Ca²⁺ celular. La modulación del transporte de Ca²⁺ mitocondrial es una estrategia prometedora para el desarrollo de terapias antiarrítmicas innovadoras.
- Generalisable computer vision methods for endoscopic surveillance and surgical interventions(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-12-05) Ali, Mansoor; Ochoa Ruiz, Gilberto; emimmayorquin, emipsanchez; School of Engineering and Sciences; Campus Estado de México; Ali, SharibAmong the most prevalent cancers in humans are gastrointestinal (GI) cancers, which mostly include cancers originating from the esophagus, stomach, and colon. Endoscopy for the upper gastrointestinal (GI) tract and colonoscopy for the lower side are considered the gold standard techniques for screening and removing precancerous lesions and abnormal tissue growth like polyps with high sensitivity. Prior research has shown higher polyp miss rates due to their peculiar morphology, variability in shape or size, and appearance. Also, endoscopic surgical interventions offer a minimally invasive approach for lesion removal or for the treatment of other diseases inside the abdominal and reproductive organs. Despite being patient-friendly in reducing trauma, hospitalisation times, and quicker post-operative recovery, minimally invasive surgeries may become complicated due to increased cognitive burden and reduced field-of-view for the clinicians. Computer-assisted detection (CADe), diagnosis (CADx), and interventions (CAI) have shown promise in providing useful support to the clinicians in both disease diagnosis and treatment, with immense potential to further improvements as the data availability becomes easier due to the endoscopes. Deep learning is increasingly being leveraged to develop methods for improving the pre-cancerous lesion detection and diagnosis, reducing the missing rates and providing intraoperative assistance to surgeons for better decision-making. However, current methods suffer from the domain shift problem, i.e., they work well on the same distribution of data and perform poorly on out-of-the-distribution data, thus lacking the real-world deployment capability. This thesis explores the impact of domain shift in endoscopic domain data on the current state-of-the-art methods, investigates the research gaps, and proposes methods for improved disease detection, surveillance, and surgical interventions with better generalisation capability. Specifically, we aim to use the feature space of the encoder networks of the state-of-the-art segmentation methods to learn discriminant information for better domain-invariant learning and improving the model generalisation on unseen out-of-the-distribution endoscopic datasets. We propose various methods for polyp segmentation in upper and lower GI tract data, full scene segmentation in laparoscopic surgery, and depth estimation in abdominal surgery. We also introduce an annotated multicentre segmentation dataset for evaluating model performance on generalisability and encouraging further research. Our results indicate improved out-of-distribution performance on multi-domain and cross-center endoscopic data. We will further work on extending the data to enhance its size and variability and explore new methods to increase robustness and generalisation performance.
- Valorization of berry by-products and waste based on a circular bioeconomy scheme: generation of prototypes and their biological and functional characterization(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-12-03) Hurtado Romero, Alejandra; García Cayuela, Tomás; mtyahinojosa, emipsanchez; Rodríquez Martínez, Verónica; Luzardo Ocampo, Iván; Paloma Barajas Álvarez; Zárate, Gabriela; García Amézquita, Luis Eduardo; Escuela de Ingeniería y Ciencias; Campus Guadalajara; Carrillo Nieves, DanayMexico is a global leader in berry production; however, the industry faces significant challenges in managing the considerable waste generated throughout the production chain. Large amounts of skins, pulp, and seeds, known as berry bagasse, remain underutilized. These residues are often discarded without treatment, resulting in the loss of valuable phytochemicals. Consequently, the development of effective strategies for the valorization of berry by-products is urgently required. Recent studies indicate that berry bagasse retains substantial levels of sugars, phenolic compounds, and other bioactive molecules, making it a promising source of functional ingredients. Comprehensive analyses of strawberry, raspberry, blueberry, and blackberry by-products have identified a wide variety of phenolic compounds, with blackberry bagasse exhibiting particularly strong antimicrobial activity. Moreover, several probiotic strains, including Lacticaseibacillus rhamnosus GG and Lentilactobacillus kefiri BIOTEC014, can utilize strawberry and blueberry bagasses as carbon sources. Solid-state fermentation (SSF) has also emerged as an innovative strategy to improve the bioactivity of blueberry residues. SSF with Aspergillus niger ATCC 6275 and Rhizopus oryzae BIOTEC018 significantly increases the release of bound phenolics, enhancing the antioxidant and anti-inflammatory potential of the resulting extracts. This approach enables the generation of metabolites with notable biological benefits and offers valuable opportunities for nutraceutical and biofortified food applications. The incorporation of berry by-products into dairy matrices further demonstrates their industrial potential. Blueberry bagasse powder and syrup have been successfully integrated into synbiotic Petit Suisse cheese, increasing fiber content, improving antioxidant capacity, and maintaining probiotic viability during storage. Sensory evaluations show high consumer acceptance, particularly in formulations combining both syrup and bagasse. Likewise, frozen dairy snacks enriched with blueberry bagasse and probiotics exhibit high nutritional quality, increased dietary fiber, strong antioxidant activity, and excellent probiotic stability during freezing and digestion. These products also receive strong consumer approval, reinforcing the feasibility of using berry residues to develop functional and sustainable foods. Overall, the valorization of berry by-products represents a sustainable strategy to reduce waste while generating high-value functional ingredients and innovative food products.
- Design of novel oven-baked sweet potato snack enhanced with brewery byproduct: the effect on sensory and nutritional content(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-12-03) Gómez Cisneros, Analaura; Calderón Oliver, Mariel; emimmayorquin, emipsanchez; Escalante Alburto, Anayansi; Pino Espinosa Ramírez, Johanan del; Ponce Alquicira, Edith; School of Engineering and Sciences; Campus Monterrey; Santos Sea, LilianaThis doctoral thesis investigates the potential of converting sweet potatoes into flour and analyzes how different drying techniques affect the preservation of bioactive compounds. It also assesses the role of ultrasound as a pretreatment strategy to improve the content of these compounds during processing. The obtained flour was subsequently used on the design of a novel baked snack enriched with brewer's spent grain (BSG), a by-product of the brewing industry, to evaluate the effects of this enrichment on its sensory and nutritional attributes. The main motivation lies in the growing demand for more nutritious snacks and the valorization of agro-industrial by-products. The general objective was to apply and evaluate the effects of ultrasound, storage, and drying methods in the processing of sweet potato to obtain flour with increased phenolic and carotene content, and to use it as an ingredient in an oven-baked snack enriched with BSG, aiming to achieve improved nutritional properties and acceptable sensory characteristics. The methodology included the production of sweet potato flour (SPF), evaluation of the effect of ultrasound treatment, different storage times (0, 24, 48, 72, and 96 h), and drying methods (dehydration and freeze-drying) on the content of bioactive compounds (phenolics and carotenoids), and physicochemical properties. Subsequently, a base snack was formulated using the produced sweet potato flour with corn flour and wheat flour, and the proportions were optimized through mixture design, based on sensory evaluation, and texture analysis. Finally, different proportions of ground BSG (6.25%, 12.5%, 18.75%, and 25%) were added to the base snack to evaluate its impact on sensory properties, color, texture, nutritional composition (moisture, fat, protein, fiber, ash, starch), and content of bioactive compounds (phenolics, carotenoids, and antioxidant activity). The results showed that ultrasound treatment significantly affected the polyphenol content of sweet potato flour, increasing it by 93%, highlighting the effectiveness of US as an abiotic elicitor for the accumulation of phenolic compounds even in processed foods. The drying method influenced the carotenoid content, achieving 65% more content when the samples were freeze-dried. In addition, the b* and L* values were affected by these two factors, resulting in higher values for both parameters. The processing methodology was defined as the use of US-pretreatment, storage for 48 h and dehydration, and the produced flour was used to develop a novel oven-baked snack with nixtamalized corn (CF) and wheat flour (WH). The optimal formulation consisted of 28.29% SPF, 41.45% CF, and 30.3% WF, achieving satisfactory overall acceptability with a score of 7.05±0.22 ("moderate liking"). The addition of BSG (up to 25%) to the optimized formula significantly modified the color by reducing the a* and b* values, and texture by increasing the hardness, gumminess, and chewiness of the snack. However, the overall sensory acceptance according to the hedonic scale remained at acceptable levels with scores above 6, defined as like slightly, even with the addition of up to 25% BSG. Nutritional analysis showed that adding BSG significantly increased 1.6 more times of dietary fiber and double the ash content, as well as three times more in the phenolic content and 33% more in antioxidant activity of the snack. The formulation containing 6.25% BSG proved to be the best final formula, offering the greatest balance between improved nutritional properties and favorable sensory attributes, with the highest overall acceptability score. Overall, this work brings together two main contributions: first, it proposes a novel processing strategy for sweet potato that combines ultrasound, cold storage, and dehydration, which resulted in a flour with enhanced bioactive content. Rather than limiting the contribution to improved flour, the study extends this development into an oven-baked snack that aligns with consumer demand for more nutritious foods. The combination of the produced sweet potato flour with corn, wheat, and brewer’s spent grain represents a mixture that has been scarcely explored, and working with it provided new information on how they can improve the nutritional profile of an oven-baked snack. These findings not only offer a promising direction for new added-value snack products but also respond to current trends in health-focused eating and sustainable food development. By valorizing an agro-industrial by-product and incorporating plant-based ingredients, the final product contributes to more responsible and forward-looking food systems.
- Nutritional and functional characterization of mexican medicinal plants : Ludwigia octovalvis, Cnidoscolus aconitifolius, and Crotalaria longirostrata, with implications for food system integration and glycemic response reduction(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-11-30) Ramos Calónico, Kimberly Andrea; Rosa Millán, Julián de la; Vázquez Lepe, Elisa Virginia; mtyahinojosa; Ramírez Jiménez, Aurea Karina; Cardador Martínez, Ma. Anaberta; Luna Vital, Diego Armando; Ovando Martínez, Maribel; Santos Zea, Liliana; School of Engineering and Sciences; Campus MonterreyThis dissertation investigates the potential of three underutilized Mexican medicinal plants—Ludwigia octovalvis (Jacq.) P.H. Raven, Cnidoscolus aconitifolius, and Crotalaria longirostrata—to improve the nutritional quality, physicochemical properties, and predicted glycemic response of wheat-based bread. The research integrates biochemical, structural, and technological evaluations across three peer-reviewed studies. The first stage characterizes the chemical composition, phenolic profile, and in vitro inhibitory activity of the plants against key digestive enzymes (α-amylase, α-glucosidase, lipase, and pepsin), establishing their metabolic relevance and bioactive potential. The second stage evaluates the incorporation of plant flours into wheat dough (5% w/w), examining gluten functionality, dough rheology, phenolic–protein interactions, and microstructural modifications during fermentation. The third stage assesses the nutritional composition, dietary fiber fractions, starch digestibility (RDS, SDS, RS), and predicted glycemic index (pGI) of breads enriched with C. aconitifolius and C. longirostrata, using standardized in vitro digestion protocols. Collectively, the findings demonstrate that these medicinal plants modulate dough development, influence starch digestion kinetics, and can effectively reduce the pGI of bread through combined mechanisms of enzymatic inhibition and matrix driven structural modifications. This work provides a mechanistic and formulation based foundation for the development of functional foods derived from ethnobotanically relevant Mexican species, contributing to dietary strategies aimed at reducing postprandial glycemic responses.
- Investigating the impact of CD16b on the functional responses in human neutrophils(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-09-01) Cruz Cárdenas, José Antonio; Brunck, Marion Emilie Genevieve; emimmayorquin, emipsanchez; Rodríguez González, Mabel; Schnoor, Michael; Antunez Ricardo, Marilena; Vazquez Garza, Eduardo; Fernandes, Maria; Escuela de Ingeniería y Ciencias; Campus MonterreyNeutrophils rely on Fc gamma receptors (FcgRs) to recognize IgG-opsonized pathogens, initiating antimicrobial functions such as phagocytosis, reactive oxygen species (ROS) production, cytokine release, and SYK-dependent signaling. CD16b (FcgRIIIb), the most abundant FcgR on human neutrophils, is a GPI-anchored receptor lacking an intracellular domain, and its signaling mechanisms remain poorly understood. The rarity of CD16b deficient neutrophils in the population (<1%) limits direct investigation in primary cells. To address this, we generated HL-60–derived neutrophil-like cell lines with CRISPR/Cas9 mediated deletion of either CD16b or CD32a (FcgRIIa) and performed functional assays including phagocytosis, ROS production, SYK phosphorylation, and cytokine profiling. Both CD16b-/- and CD32a-/- HL-60-derived clones differentiated normally into neutrophil-like cells and retained phagocytic capacity. However, FcgR-mediated ROS production and SYK activation were significantly impaired, particularly in CD16b-deficient cells. Cytokine responses were altered in a receptor-specific manner: CD16b-/- cells produced less IL-6 and IL-1β, whereas CD32a-/- cells produced less TNF-α and IL-10. These results highlight the distinct contributions of CD16b and CD32a to neutrophil effector functions and immune regulation. Complementing the model, we identified two healthy brothers naturally lacking CD16b on their neutrophils. Sequencing revealed mutations in exon 2 of FCGR3B resulting in loss of protein expression. FcgRIIIbnull neutrophils exhibited compensatory upregulation of CD16a and CD64 but showed impaired phagocytosis, ROS production, actin polymerization, and SYK-dependent signaling following stimulation with opsonized E. coli. Altered surface expression of FcgRIa, TLR-4, and CD11b was also observed upon bacterial challenge, suggesting broader regulatory effects of CD16b on neutrophil activation. Overall, this study combines engineered cellular models and rare human phenotypes to demonstrate that CD16b is a critical regulator of neutrophil antimicrobial functions and signaling. These findings provide mechanistic insight into FcgR biology and establish platforms for future investigation of receptor-specific contributions to neutrophil functions.
- Development of biosensor-based diagnostic systems for breast cancer using biorecognition engineering techniques and machine learning approaches for biomarker discovery(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-07-25) Mayoral Peña, Kalaumari; De Donato Capote, Marcos; emipsanchez; Artzi, Natalie; Víctor Manuel Treviño Alvarado; Alfaro Ponce, Mariel; School of Engineering and Sciences; Campus Monterrey; González Peña, Omar IsraelCancer is the second cause of mortality worldwide, while breast cancer is the second leading cause of global female mortality. Diagnosing and treating breast cancer patients at early stages is relevant for successful treatment and increasing the patient's survival rate. However, early diagnosis of this complex disease is challenging, especially in populations with limited healthcare services. As a result, developing more accessible and accurate diagnostic tools is necessary. The development of low-cost biosensor technologies that have been relevant in the last two decades, but these technologies are still in the process of reaching maturity. For these reasons, we decided to study two promising technologies that can be implemented in cancer biosensor development: 1) biorecognition engineering techniques; 2) machine learning approaches for biomarker discovery. The first technology comprises alternative techniques to generate molecules and molecule-based scaffolds with similar properties to those presented by antibodies. In this study, we presented a systematic analysis of the scientific peer-reviewed literature in the Web of Science from the last two decades to present the fundamentals of this technology and address questions about how it has been implemented in biosensors for cancer detection. The three techniques analyzed were molecularly imprinted polymers, recombinant antibodies, and antibody mimetic molecules. The PRISMA methodology included 131 scientific from 2019 to 2021 for further analysis. The results showed that antibody mimetic molecules technology was the biorecognition technology with the highest number of reports. The most studied cancer types were: multiple, breast, leukemia, colorectal, and lung. Electrochemical and optical detection methods were the most frequently used. Finally, the most analyzed biomarkers and cancer entities in the studies were carcinoembryonic antigen, MCF-7 cells, and exosomes. For the second technology, we developed a novel bioinformatics pipeline that uses machine learning algorithms (MLAs) to identify genetic biomarkers for classifying breast cancer into non-malignant, non-triple-negative, and triple-negative categories. Five Gene Selection Approaches (GSAs) were employed: LASSO (Least Absolute Shrinkage and Selection Operator), Membrane LASSO, Surfaceome LASSO, Network Analysis, and Feature Importance Score (FIS). We implemented three factorial designs to assess the impact of MLAs and GSAs on classification performance (F1 Macro and Accuracy) in both cell lines and patient samples. Using Recursive Feature Elimination (RFE) and Genetic Algorithms (GAs) in the first four GSAs, we reduced the gene count to eight per GSA while maintaining an F1 Macro ≥ 80%. Consequently, 95.5% of our treatments with these gene sets achieved an F1 Macro or Accuracy ranging from 70.3% to 97.2%. As a result, 37 different genes were obtained. We analyzed the 37 genes for their predictive power in terms of five-year survival and relapse-free survival and compared them with genes from four commercial panels. Notably, thirteen genes (MFSD2A, TMEM74, SFRP1, UBXN10, CACNA1H, ERBB2, SIDT1, TMEM129, MME, FLRT2, CA12, ESR1, and TBC1D9) showed significant predictive capabilities for up to five years of survival. TBC1D9, UBXN10, SFRP1, and MME were significant for relapse-free survival after five years. The FOXC1, MLPH, FOXA1, ESR1, ERBB2, and SFRP1 genes also matched those described in commercial panels. The influence of MLA on F1 Macro and Accuracy was not statistically significant. Altogether, the genetic biomarkers identified in this study hold potential for use in biosensors aimed at breast cancer diagnosis and treatment. We concluded that both technologies had demonstrated their utility in cancer biosensor development for vulnerable populations with limited access to healthcare. However, further studies are required, and a long road exists to establish a commercial biosensor. For this reason, we generated a research proposal to develop a biosensor integrating this study's information in an optical and electrochemical sensing platform. Also, some designs of this biosensor and preliminary results are presented.
- Comprehensive analysis of integrated processing approaches for chickpeas: enhancing nutritional, functional and bioactive attributes for novel plant-based beverage base(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-06-16) Ruiz Zambrano, Nidia Leticia; Pérez Carrillo, Esther; emipsanchez; Tejada Ortigoza, Viridiana Alejandra; Antunes Ricardo, Marilena; Luna Vital, Diego; Tobías Espinoza, Jazmin Leticia; Gasparre, Nicola; Escuela de Ingeniería y Ciencias; Campus Monterrey; Serna Saldívar, Sergio Román OthónThe increasing demand for plant-based beverages requires exploring different sources and processing strategies for developing nutritional and functional products. The present dissertation comprises four manuscripts focused on the effect of processing strategies on chickpeas and chickpea ingredients to produce plant-based beverages or powder beverage bases. Processing strategies assessed herein included the combination of extrusion with enzymatic hydrolysis to obtain a chickpea beverage base. This beverage base was further processed by either drying it for convenient handling or fermenting it to develop potential probiotic products. The first manuscript, titled Effect of thermal, nonthermal, and combined treatments on functional and nutritional properties of chickpeas comprises a critical literature review that synthetizes the effects of thermal, non-thermal, and combined processing strategies on chickpea functional and nutritional properties. This provides a wide understanding of the modifications induced and highlights the necessity of carefully selecting processing methods to achieve desired end-product attributes. Further experimental studies are necessary to comprehensively assess the effect of spry drying and fermentation on the novel chickpea hydrolysate and its suitability for beverage formulations. The research presented in the second manuscript, Effect of spray-drying or fermentation on the solubility and carbohydrate profile of chickpea hydrolysates for beverage formulation, demonstrated that spray-drying induced a more amorphous structure with reduced particle sizes, and improved suspension stability compared to freeze-drying, conferring attributes beneficial for plant-based beverages. Meanwhile, lactic acid fermentation prior to freeze-drying promotes higher crystallinity, larger particle sizes, and less stable suspensions in contrast with the freeze-dried beverage base. Solids separation, a previous step included in the processing strategy, made soluble dietary fraction predominant in all cases, contributing to the overall high solubility. Spray-drying with adjuvants and fermentation induced reductions in starch and raffinose family oligosaccharides contents. Processing strategies could also induce different modifications on the antinutrients and phenolic compounds of the beverage, which were evaluated in the third manuscript, Effects of spray-drying and uses of inulin and maltodextrin as adjuvants on phenolics, bioaccessibility, and in vitro glucose consumption modulation in HepG2 cells of extrudate chickpea hydrolysate powderized. Findings indicated differences in the antinutrients concentration, phenolic compounds profile and concentrations, along with the effect in glucose consumption in an insulin resistant model of HepG2 cells related to spray-drying without adjuvants or in addition of inulin and maltodextrin, with spray-drying with inulin showing overall best performance. Furthermore, the effect of extrusion in reducing tannins and trypsin inhibitor activity was also mentioned. A different approach was evaluated in the fourth manuscript, Development of chickpea beverages through enzymatic treatments: from rapid visco analyser to pilot plant production, which focused on a practical pathway for scalable chickpea beverage production. This work demonstrated the potential of Rapid Visco Analyzer as an efficient laboratory-scale tool for optimizing enzymatic hydrolysis aimed at viscosity reduction of starch-containing ingredients like chickpeas, for plant-based beverages. This work demonstrated the direct translatability of lab-scale RVA findings to pilot plant production, achieving consistent physicochemical properties comparable to those observed in previous laboratory trials. This dissertation demonstrated the importance of tailored processing in enhancing the value of chickpeas. It provides valuable information on various processing methods for chickpea-based beverages and powdered beverage bases, which are helpful for the food industry in developing novel, nutritious, and potentially beneficial chickpea-based products for the plant-based beverage market.
- Local immunomodulatory strategies to enhance allogeneic pancreatic islet engraftment in a vascularized subcutaneous platform for the treatment of type 1 diabetes(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-06-13) Campa Carranza, Jocelyn Nikita; Cuevas Díaz Durán, Raquel; emipsanchez; Nichols, Joan E.; Zavala Arcos, Judith; Lozano García, Omar; Escuela de Medicina y Ciencias de la Salud; Campus Monterrey; Grattoni, AlessandroType 1 diabetes (T1D) is an autoimmune disease marked by pancreatic β-cell destruction, leading to lifelong dependence on exogenous insulin therapy. Pancreatic islet transplantation offers a functional cure, but clinical application is limited by poor graft engraftment, hypoxia-related cell loss, and dependence on chronic systemic immunosuppression. This thesis investigates local immunomodulation approaches to improve allogeneic islet engraftment in a vascularized subcutaneous platform, the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device. Specifically, it evaluates the immunomodulatory and proangiogenic roles of mesenchymal stem cells (MSCs) and the localized delivery of clinically relevant immunosuppressive agents. Experiments were conducted in immunocompetent diabetic rats, with sex included as a biological variable. MSC-loaded NICHE devices promoted robust vascularization and improved islet engraftment, even in the context of diabetes-associated vascular dysfunction. High-dimensional immune profiling demonstrated that MSCs transiently reduced innate immune infiltration and inflammatory cytokines and preserved regulatory T cells. Sex-specific differences were observed, with female rats exhibiting improved vascularization and immune regulation. Additionally, local immunosuppression was explored revealing different immunomodulatory profiles, and drug retention at the graft site with minimal systemic exposure. Together, this work supports a combinatorial local immunomodulation approach integrating MSCs and targeted immunosuppression. The NICHE platform provides a clinically relevant strategy for long-term islet engraftment without systemic immunosuppression, advancing safer, more effective therapies for T1D.
- PLA coating technologies for next-generation coronary stents: dip coating, spray coating, and electrospinning(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2025-06-12) Macías Naranjo, Mariana; Vázquez Lepe, Elisa Virginia; emipsanchez; Rodríguez González, Ciro Ángel; Sánchez Domínguez, Margarita; Tejeda Alejandre, Raquel; Vázquez Armendáriz, Javier Oswaldo; School of Engineering and Sciences; Campus Monterrey; García López, ErikaCurrently, various diseases are caused by the occlusion of ducts in the body. One of the most common and recurring solutions is the implantation of stents. This surgical intervention, called angioplasty, involves placing a stent in a blocked vessel to restore blood flow. Although early-generation stents made of metallic alloys, such as stainless steel (SS), demonstrated excellent mechanical properties, they are not biodegradable and often lead to long-term complications, including neointimal proliferation and chronic inflammation. As a result, polymeric coatings have been introduced to improve biocompatibility and serve as drug reservoirs. However, challenges remain in achieving optimal surface properties, such as uniformity, low roughness, and controlled thickness, which are critical for stent performance and hemocompatibility. This thesis examines three polymer coating techniques—dip coating, spray coating, and electrospinning—and assesses their effectiveness in meeting these requirements. The first article investigates dip coating using stainless steel (SS) substrates and evaluates the impact of process parameters on coating uniformity, roughness, and thickness. The second article introduces electrospinning as a method to create nanofibrous PLA coatings on SS stents, highlighting those process parameters involved in the impact of fiber diameter and surface coverage. The third article extends this approach to magnesium-based stents (WE43 alloy), addressing the additional requirement of controlling degradation rates for biodegradable applications. The last article focuses on spray coating, examining how variations in flow rate, spraying time, spraying distance, rotational speed, and inlet air pressure influence coating morphology. Altogether, this research provides a comprehensive evaluation of coating technologies for next-generation coronary stents, aiming to optimize surface characteristics to improve biocompatibility, mechanical performance, and degradation control.