Multifunctional Biomimetic Scaffolds Tailored for Cardiac Regeneration
Notice bibliographique
Résumé
Nature has had millions of years to perfect the structural components of the human body, but has also produced the dysfunctions that result in the cancers and diseases, which ruin that perfection.Congenital heart defects, and myocardial infarction lead to scarring that remodels heart muscle, decreasing the contractility of the heart, with profound consequences for the host.Regenerative medicine is the study of strategies to return diseased body parts to their evolutionarily optimum structure.Cells alone cannot develop into functional tissue, as they require mechanical support and chemical signals from the extracellular matrix in order to play the correct role in the body.In order to imitate the process of tissue formation optimized by nature, scaffolds are developed as the architectural support for tissue regeneration.To mimic the elasticity and strength seen in the heart muscle is one of the major scientific conundrums of our time.The development of new multifunctional materials for scaffolds is an accepted solution for repairing failing heart muscle.In this thesis I accept the notion that endogenous cardiac cells can play a major role in addressing this problem, if we can attract them to the site of defect or injury and make them proliferate.I then proceed to show how improving on a commonly used synthetic polymer was used to develop two new biomaterials.Polycaprolactone (PCL) fibers and sheets were studied for their ability to adsorb proteins based on their surface energies.We found that although the wettability of the PCL might be similar to positive controls for cell attachment, the large differences in surface energies may account for the increased serum protein adsorption and limit cell adhesion.The effect of fiber morphology was then investigated with respect to proliferation of mesenchymal stem cells and cardiac progenitor cells.PCL was also mechanically enhanced with thiophene conjugated single walled carbon nanotubes (T-CNT); where small concentrations of the T-CNT allowed for a 2.5 fold increase in the percentage of elongation, while retaining the proliferation profile of the cardiac progenitor cells.Although PCL is a well-known implant material, the ability to attract and adhere cardiac cells was limited.Therefore we sought to develop new biomaterials with fiber morphologies similar to the muscle fiber of the heart, but with surface energies similar to positive controls for cell attachment.Poly[2,3-bis-(3iii octyloxyphenyl)quinoxaline-5,8-diyl-alt-thiophene-2,5-diyl] (TQ1) was then explored as a ribbon fiber and compared to collagen with embryonic cardiac cells, in vitro, and then implanted into rats for in vivo long term evaluations.The cardiac cells had a preferential adhesion to the TQ1 fibers, and in vivo the fibers attracted more blood vessels and regrew functional tissue compared to the collagen controls.TQ1 fibers had the added ability to emit light in the near infrared region, which would allow for consistent tracking of the material.Although this material offered the morphological preference for the cardiac cells, it does not degrade nor did it offer electrical conductivity.The heart muscle is an electrically active muscle.The dead tissue that is formed in the ischemic area loses its ability to transfer the electrical signals.Hence, I have then developed collagen fibrous materials with silver nanowires to help store and inject charges that would be generated during the contraction of the heart muscle.The silver nanowires served to help carry charges whilst providing resistance to bacterial growth on the material.The collagen/silver nanowires composites were mechanically apt for the culture of embryonic cardiac cells.This thesis promotes the idea that morphology and favorable surface energies can help to attract and retain cardiac cells.It also shows the ability to manipulate materials to provide different functionalities, without losing their biocompatibility.I have added one new highly functional biomaterial to the list of materials capable of mimicking the extracellular matrix.I have also shown that small additions of metallic nanowires to a collagen matrix can increase its ability to conduct electrical signals, whilst retaining the mechanical properties that cardiac cells prefer.With the help of doctors and biomedical scientists, the materials of this thesis will hopefully translate to help patients have a better quality of life after heart injury.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».