Concept Mapping as a Metacognition Tool in a Problem-Solving-Based BME Course During In-Person and Online Instruction.

Metacognitive skills can have enormous benefits for students within engineering courses. Unfortunately, these metacognitive skills tend to fall outside the content area of most courses, and consequently, they can often be neglected in instruction. In this context, previous research on concept mapping as a teaching strategy points to meaningful learning. The purpose of this innovation paper is to report an application of concept mapping (1) to facilitate metacognition steps in students, and (2) to identify the muddiest points students struggle with, during both in-person and online instruction of a problem-solving-based biomedical engineering course. This innovation article also looks at the usefulness of concept mapping through instructor and student perceptions and students' class performance. The entire concept mapping intervention was conducted during weeks 8-10 of the Spring 2019 in-person quarter and during weeks 3-4 and 8-10 of the Spring 2021 online quarter. The exercise involved concept mapping, explanation and discussion with peers, and answering structured reflection prompts. Each concept map activity was contextualized to the metacognitive knowledge domain of the revised Bloom's taxonomy. The average class performance was compared between students who completed concept mapping vs. those who did not, using a t-test and one-way ANOVA at alpha = 0.05 significance level followed by a Tukey HSD test. Students' concept maps and reported answers were analyzed qualitatively following the concept mapping intervention. During the Spring 2019 in-person quarter, 59.30% of students completed concept mapping with reflection, whereas 47.67% completed it in spring 2021 online instruction. A two-tailed, unpaired t-test indicated that concept mapping did not significantly enhance students' class performance (p > 0.05) within each of the in-person and online instructions. Peers' suggestions to students to improve concept maps revealed themes related to course concepts, prerequisite concepts, and the act of concept mapping itself. Concept mapping was effective in revealing the muddiest points of the course. Concept mapping did not significantly enhance students' class performance either in-person or online instruction (effect sizes were 0.29 for the 2019 in-person quarter and 0.33 for the 2021 online quarter). However, instructors and students' perceptions reflected that concept mapping facilitated metacognition in a problem-solving-based biomedical engineering course both during in-person and online instruction. Most students (78%) were optimistic about the usefulness of concept mapping for this course, and 84% were inclined to apply it for a variety of other courses. Supplementary Information: The online version contains supplementary material available at 10.1007/s43683-022-00066-3.

Isolating and characterizing lymphatic endothelial progenitor cells for potential therapeutic lymphangiogenic applications.

Lymphatic dysfunction is associated with the progression of several vascular disorders, though currently, there are limited strategies to promote new lymphatic vasculature (i.e., lymphangiogenesis) to restore lost lymphatic function. One promising approach to stimulate lymphangiogenesis involves delivering endothelial progenitor cells (EPCs), which are naturally involved in de novo blood vessel formation and have recently been identified to include a lymphatic subpopulation. However, the contribution of lymphatic EPCs in lymphangiogenesis is not clear and challenges with maintaining the activity of transplanted EPCs remain. Thus, the objective of this study was to isolate lymphatic EPCs from human umbilical cord blood and characterize their role in the initial stages of blood or lymphatic vasculature formation. Furthermore, this study also tested the applicability of alginate hydrogels to deliver lymphatic EPCs for a possible therapeutic application. We postulated and confirmed that blood and lymphatic EPC colonies could be isolated from human umbilical cord blood. Additionally, EPC populations responded to either angiogenic or lymphangiogenic growth factors and could stimulate their respective mature endothelial cells in vasculature models in vitro. Finally, lymphatic EPCs maintained their ability to promote lymphatic sprouts after prolonged interactions with the alginate hydrogel microenvironment. These results suggest EPCs have both a blood and a lymphatic population that have specific roles in promoting revascularization and highlight the potential of alginate hydrogels for the delivery of lymphatic EPCs. STATEMENT OF SIGNIFICANCE: Despite the potential therapeutic benefit of promoting lymphatic vasculature, lymphangiogenesis remains understudied. One appealing strategy for promoting lymphangiogenesis involves delivering lymphatic endothelial progenitor cells (EPCs), which are a subpopulation of EPCs involved in de novo vessel formation. Here, we investigate the role of isolated blood and lymphatic EPC subpopulations in promoting the early stages of vascularization and the utility of alginate hydrogels to deliver lymphatic EPCs. We determined that EPCs had two populations that expressed either blood or lymphatic markers, could stimulate their respective mature vasculature in tissue constructs and that alginate hydrogels maintained the therapeutic potential of lymphatic EPCs. We anticipate this work could support promising biomaterial applications of EPCs to promote revascularization, which could have many therapeutic applications.

Computational-Based Design of Hydrogels with Predictable Mesh Properties.

Hydrogel systems are an appealing class of therapeutic delivery vehicles, though it can be challenging to design hydrogels that maintain desired spatiotemporal presentation of therapeutic cargo. In this work, we propose a different approach in which computational tools are developed that creates a theoretical representation of the hydrogel polymer network to design hydrogels with predefined mesh properties critical for controlling therapeutic delivery. We postulated and confirmed that the computational model could incorporate properties of alginate polymers, including polymer content, monomer composition and polymer chain radius, to accurately predict cross-link density and mesh size for a wide range of alginate hydrogels. Additionally, the simulations provided a robust strategy to determine the mesh size distribution and identified properties to control the mesh size of alginate hydrogels. Furthermore, the model was validated for additional hydrogel systems and provided a high degree of correlation (R2 > 0.95) to the mesh sizes determined for both fibrin and polyethylene glycol (PEG) hydrogels. Finally, a full factorial and Box-Behnken design of experiments (DOE) approach utilized in combination with the computational model predicted that the mesh size of hydrogels could be varied from approximately 5 nm to 5 µm through controlling properties of the polymer network. Overall, this computational model of the hydrogel polymer network provides a rapid and accessible strategy to predict hydrogel mesh properties and ultimately design hydrogel systems with desired mesh properties for potential therapeutic applications.

Thaw-Induced Gelation of Alginate Hydrogels for Versatile Delivery of Therapeutics.

Alginate hydrogels have been extensively used and successfully validated as delivery vehicles of bioactive factors in many tissue engineering applications. This work describes and characterizes a singular alternative method to create alginate hydrogels designated as thaw-induced gelation (TIG). The TIG method involves gelation through the time-dependent release of the polymer or crosslinker by melting into solution. Alginate TIG hydrogels were validated for spatial-temporal control delivery of different cargos including albumin, dextran, and doxorubicin. Chitosan was incorporated into TIG hydrogels to investigate the electrostatic interactions between alginate and the tested cargos. Interestingly, while 90% of doxorubicin was released after 8 h from hydrogels formed with frozen calcium, hydrogels formulated from frozen alginate took 72 h. In addition, the storage modulus of TIG hydrogels prepared from frozen alginate was double that of a hydrogel formed without freezing alginate. Therefore, the utility of TIG strategies are particularly promising for the delivery of therapeutic cargos smaller than the mesh size of the alginate hydrogel, as it enables controlled release of these cargos without any further chemical modifications of the hydrogels. These TIG alginate hydrogels with tunable mechanical properties and control over the delivery of smaller cargos could be useful in many tissue engineering applications.

Alginate hydrogels allow for bioactive and sustained release of VEGF-C and VEGF-D for lymphangiogenic therapeutic applications.

Lymphatic dysfunction is associated with the progression of many cardiovascular disorders due to their role in maintaining tissue fluid homeostasis. Promoting new lymphatic vessels (lymphangiogenesis) is a promising strategy to reverse these cardiovascular disorders via restoring lymphatic function. Vascular endothelial growth factor (VEGF) members VEGF-C and VEGF-D are both potent candidates for stimulating lymphangiogenesis, though maintaining spatial and temporal control of these factors represents a challenge to developing efficient therapeutic lymphangiogenic applications. Injectable alginate hydrogels have been useful for the controlled delivery of many angiogenic factors, including VEGF-A, to stimulate new blood vasculature. However, the utility of these tunable hydrogels for delivering lymphangiogenic factors has never been closely examined. Thus, the objective of this study was to utilize ionically cross-linked alginate hydrogels to deliver VEGF-C and VEGF-D for potential lymphangiogenic applications. We demonstrated that lymphatic endothelial cells (LECs) are sensitive to temporal presentation of VEGF-C and VEGF-D but with different responses between the factors. The greatest LEC mitogenic and sprouting response was observed for constant concentrations of VEGF-C and a high initial concentration that gradually decreased over time for VEGF-D. Additionally, alginate hydrogels provided sustained release of radiolabeled VEGF-C and VEGF-D. Finally, VEGF-C and VEGF-D released from these hydrogels promoted a similar number of LEC sprouts as exogenously added growth factors and new vasculature in vivo via a chick chorioallantoic membrane (CAM) assay. Overall, these findings demonstrate that alginate hydrogels can provide sustained and bioactive release of VEGF-C and VEGF-D which could have applications for therapeutic lymphangiogenesis.