The aim of this study was to develop drug delivery system based on poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles (NPs) to achieve personalized treatment of selected skin disorders, like photo-aging, psoriasis and atopic dermatitis. Dead Sea Water (DSW) and Retinyl Palmitate (RP) were used as active agents and they were loaded in PLGA NPs prepared either as spheres or capsules by o/w or w/o/w methods. MgCl2 and bovine serum albumin (BSA) served as model active compounds. The diameter of the NPs was found to be in the range of 280 - 550 nm. The entrapment efficiency (E.E.) was less than 1% for RP, DSW and MgCl2, and 41% for BSA. Loading of Cl- together with BSA doubled the E.E. value of Cl- . In situ release studies showed a burst in the first day and more than 85% of the chloride content was released within a week. When the macromolecule BSA was encapsulated, a much slower and triphasic release profile was observed which continued for up to 80 days. In vitro tests were performed using L929 fibroblast cells. Results of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) test revealed that none of the NPs were cytotoxic. Additionally, all particles were hemocompatible with hemolytic activity &lt / 1.5%. L929 fibroblast and Saos 2 human osteosarcoma cells were used to study the uptake of NPs by the cells. Particles accumulate near the nucleus. The characterization and cell viability tests, and drug release behavior indicate the suitability of these NPs for further testing to develop a patient specific skin diseases treatment approach.

Dexamethasone and dexamethasone 21-phosphate were loaded into NDGA-polymerized collagen fibers and release rate studies were performed to calculate their diffusion coefficients. Dexamethasone loaded fibers were placed in a PBS solution for specified time intervals (1, 3, 6, 7, 12, 24, 30, and 48 hours) after which the eluant was removed and analyzed by capillary zone electrophoresis (CZE). CZE is a tool that can be utilized for quantitative analysis of chemical compounds. This data was incorporated into mathematical models to determine the diffusion coefficient. The diffusion coefficient (D) for dexamethasone in NDGA-polymerized collagen fibers is D = 1.86 x 10⁻¹⁴ m²/s. Similarly, dexamethasone 21-phosphate loaded fibers were placed into a PBS solution and analyzed using CZE at these specified intervals (15, 30, 45, 60, and 75 minutes). Applying this data to the mathematical model provided a diffusion coefficient for dexamethasone 21-phosphate in NDGA-polymerized collagen fibers of D = 2.36 x 10⁻¹³ m²/s. In an effort to control drug delivery from these fibers a polylactic-co-glycolic acid (PLGA) coating was applied to the fibers. This coating helped sustain delivery of dexamethasone 21-phosphate for over a 100 day period. CZE experiments were again conducted in conjunction with another mathematical model to characterize release. A semi steady-state diffusion coefficient was estimated to be D = 4.59 x 10⁻¹⁴ m²/s.

Magnesium has been identified as a promising biodegradable implant material because it does not cause systemic toxicity and can reduce stress shielding. However, it corrodes too quickly in the body. Titanium, which is already used ubiquitously for implants, was chosen as the alloying element because of its proven biocompatibility and corrosion resistance in physiological environments. Thus, alloying magnesium with titanium is expected to improve the corrosion resistance of magnesium. Mg-Ti alloys with a titanium content ranging from 5 to 35 at.-% were successfully synthesized by mechanical alloying. Spark plasma sintering was identified as a processing route to consolidate the alloy powders made by ball-milling into bulk material without destroying the alloy structure. This is an important finding as this metastable Mg-Ti alloy can only be heated up to max. 200C° for a limited time without reaching the stable state of separated magnesium and titanium. The superior corrosion behavior of Mg80-Ti20 alloy in a simulated physiological environment was shown through hydrogen evolution tests, where the corrosion rate was drastically reduced compared to pure magnesium and electrochemical measurements revealed an increased potential and resistance compared to pure magnesium. Cytotoxicity tests on murine pre-osteoblastic cells in vitro confirmed that supernatants made from Mg-Ti alloy were no more cytotoxic than supernatants prepared with pure magnesium. Mg and Mg-Ti alloys can also be used to make novel polymer-metal composites, e.g., with poly(lactic-co-glycolic acid) (PLGA) to avoid the polymer’s detrimental pH drop during degradation and alter its degradation pattern. Thus, Mg-Ti alloys can be fabricated and consolidated while achieving improved corrosion resistance and maintaining cytocompatibility. This work opens up the possibility of using Mg-Ti alloys for fracture fixation implants and other biomedical applications.

A perda ou falha de um órgão ou tecido é um dos problemas mais severos da saúde humana. A engenharia de tecidos, definida como o cultivo e adesão de células humanas in vitro em um scaffold ou arcabouço, surge como uma alternativa viável para reposição de órgãos e tecidos. Estas células proliferam, migram e se diferenciam num tecido específico enquanto produzem os componentes de matriz extracelular (ECM) necessários para criar este tecido. A obtenção de scaffolds fibrosos a partir da blenda polimérica de Poli (Ácido Láctico-co-Glicólico) (PLGA) e Poliisopreno (PI) é proposta como uma alternativa à engenharia de tecidos moles. Este material foi processado como estrutura fibrosa por meio de métodos de gotejamento (FD) e electrospinning (FS). Caracterização físico-química foi aplicada à blenda e às fibras geradas. Também foi averiguada a viabilidade das fibras em culturas de mioblastos murinos, fibroblastos dérmicos humanos, condrócitos bovinos e hepatocarcinomas. Nota-se que o processo de obtenção da blenda não apresentou alterações na estrutura química dos polímeros, sendo apontada também a imiscibilidade entre eles. A ductilidade do material foi apontada como efeito da presença de PI na blenda, embora esta composição apresente similar molhabilidade entre a mistura e os polímeros puros. As fibras geradas por electrospinning geraram um scaffold com menor porosidade do que as fibras obtidas por gotejamento, mesmo apresentando um diâmetro menor e uma orientação paralela entre fibras. As fibras obtidas por gotejamento apresentaram fibras emaranhadas de maior diâmetro, mas maior tammanho de poros, gerando scaffolds de maior porosidade. As propriedades mecânicas de ambos scaffolds indicam sua aplicação enquanto substitutos de tecidos moles. Ensaios de viabilidade celular condenaram o uso das fibras FS, uma vez que estas apresentaram solvente residual no interior da fibra, causando indesejada lise celular. As fibras FD apresentaram resultados de adesão e proliferação adequados para mioblastos, fibroblastos e condrócitos, porém os resultados foram considerados impróprios para hepatócitos. / The lost or failure of an organ or tissue is one of the most severe problems in human health. Tissue engineering, defined as the seeding and adhesion of human cells in vitro over a scaffold, arises as an viable alternative for reproduction of organs and tissues. These cells proliferate, migrate and differentiate into a specific tissue while producing extracellular matrix components. The obtaining of fibrous scaffolds from a polymeric blend of Poly (Lactic-co-Glycolic Acid) (PLGA) and Polyisoprene (PI) is proposed as an alternative to soft tissue engineering. This material was processed as a fibrous structure through dripping (FD) and electrospinning (FS) methods. Physical-chemical characterization was applied to the blend and to the generated fibres. Fibres viability was also observed for murine myoblasts, human dermal fibroblasts, bovine chondrocytes and hepatocellular carcinoma cultures. It was noticed that the blending process didn't have any influence over polymer's chemical structure, being observed the immiscibility between the raw materials. Blend's ductile behaviour was pointed out as an effect of PI presence, although this mixture presents similar wettability to the one presented by these raw polymers. Fibres obtained by electrospinnig generated a scaffold with smaller porosity, even presenting fibres with smaller diameter and a parallel organized topography. The fibres obtained by dripping presented a tangled structure of thicker fibres, but assembling a scaffold with higher porosity and inner space. Mechanical properties of both scaffolds indicate their applicability as soft tissue substitutes. Cell viability assays condemn the use of FS fibres, seen that they present residual solvent trapped into the fibre, causing undesirable cell lysis. On the other hand, FD fibres presented positive adhesion and proliferation results for myoblasts, fibroblasts and chondrocytes cell lines, however the results were consider inappropriate for hepatocytes.

A perda ou falha de um órgão ou tecido é um dos problemas mais severos da saúde humana. A engenharia de tecidos, definida como o cultivo e adesão de células humanas in vitro em um scaffold ou arcabouço, surge como uma alternativa viável para reposição de órgãos e tecidos. Estas células proliferam, migram e se diferenciam num tecido específico enquanto produzem os componentes de matriz extracelular (ECM) necessários para criar este tecido. A obtenção de scaffolds fibrosos a partir da blenda polimérica de Poli (Ácido Láctico-co-Glicólico) (PLGA) e Poliisopreno (PI) é proposta como uma alternativa à engenharia de tecidos moles. Este material foi processado como estrutura fibrosa por meio de métodos de gotejamento (FD) e electrospinning (FS). Caracterização físico-química foi aplicada à blenda e às fibras geradas. Também foi averiguada a viabilidade das fibras em culturas de mioblastos murinos, fibroblastos dérmicos humanos, condrócitos bovinos e hepatocarcinomas. Nota-se que o processo de obtenção da blenda não apresentou alterações na estrutura química dos polímeros, sendo apontada também a imiscibilidade entre eles. A ductilidade do material foi apontada como efeito da presença de PI na blenda, embora esta composição apresente similar molhabilidade entre a mistura e os polímeros puros. As fibras geradas por electrospinning geraram um scaffold com menor porosidade do que as fibras obtidas por gotejamento, mesmo apresentando um diâmetro menor e uma orientação paralela entre fibras. As fibras obtidas por gotejamento apresentaram fibras emaranhadas de maior diâmetro, mas maior tammanho de poros, gerando scaffolds de maior porosidade. As propriedades mecânicas de ambos scaffolds indicam sua aplicação enquanto substitutos de tecidos moles. Ensaios de viabilidade celular condenaram o uso das fibras FS, uma vez que estas apresentaram solvente residual no interior da fibra, causando indesejada lise celular. As fibras FD apresentaram resultados de adesão e proliferação adequados para mioblastos, fibroblastos e condrócitos, porém os resultados foram considerados impróprios para hepatócitos. / The lost or failure of an organ or tissue is one of the most severe problems in human health. Tissue engineering, defined as the seeding and adhesion of human cells in vitro over a scaffold, arises as an viable alternative for reproduction of organs and tissues. These cells proliferate, migrate and differentiate into a specific tissue while producing extracellular matrix components. The obtaining of fibrous scaffolds from a polymeric blend of Poly (Lactic-co-Glycolic Acid) (PLGA) and Polyisoprene (PI) is proposed as an alternative to soft tissue engineering. This material was processed as a fibrous structure through dripping (FD) and electrospinning (FS) methods. Physical-chemical characterization was applied to the blend and to the generated fibres. Fibres viability was also observed for murine myoblasts, human dermal fibroblasts, bovine chondrocytes and hepatocellular carcinoma cultures. It was noticed that the blending process didn't have any influence over polymer's chemical structure, being observed the immiscibility between the raw materials. Blend's ductile behaviour was pointed out as an effect of PI presence, although this mixture presents similar wettability to the one presented by these raw polymers. Fibres obtained by electrospinnig generated a scaffold with smaller porosity, even presenting fibres with smaller diameter and a parallel organized topography. The fibres obtained by dripping presented a tangled structure of thicker fibres, but assembling a scaffold with higher porosity and inner space. Mechanical properties of both scaffolds indicate their applicability as soft tissue substitutes. Cell viability assays condemn the use of FS fibres, seen that they present residual solvent trapped into the fibre, causing undesirable cell lysis. On the other hand, FD fibres presented positive adhesion and proliferation results for myoblasts, fibroblasts and chondrocytes cell lines, however the results were consider inappropriate for hepatocytes.

A perda ou falha de um órgão ou tecido é um dos problemas mais severos da saúde humana. A engenharia de tecidos, definida como o cultivo e adesão de células humanas in vitro em um scaffold ou arcabouço, surge como uma alternativa viável para reposição de órgãos e tecidos. Estas células proliferam, migram e se diferenciam num tecido específico enquanto produzem os componentes de matriz extracelular (ECM) necessários para criar este tecido. A obtenção de scaffolds fibrosos a partir da blenda polimérica de Poli (Ácido Láctico-co-Glicólico) (PLGA) e Poliisopreno (PI) é proposta como uma alternativa à engenharia de tecidos moles. Este material foi processado como estrutura fibrosa por meio de métodos de gotejamento (FD) e electrospinning (FS). Caracterização físico-química foi aplicada à blenda e às fibras geradas. Também foi averiguada a viabilidade das fibras em culturas de mioblastos murinos, fibroblastos dérmicos humanos, condrócitos bovinos e hepatocarcinomas. Nota-se que o processo de obtenção da blenda não apresentou alterações na estrutura química dos polímeros, sendo apontada também a imiscibilidade entre eles. A ductilidade do material foi apontada como efeito da presença de PI na blenda, embora esta composição apresente similar molhabilidade entre a mistura e os polímeros puros. As fibras geradas por electrospinning geraram um scaffold com menor porosidade do que as fibras obtidas por gotejamento, mesmo apresentando um diâmetro menor e uma orientação paralela entre fibras. As fibras obtidas por gotejamento apresentaram fibras emaranhadas de maior diâmetro, mas maior tammanho de poros, gerando scaffolds de maior porosidade. As propriedades mecânicas de ambos scaffolds indicam sua aplicação enquanto substitutos de tecidos moles. Ensaios de viabilidade celular condenaram o uso das fibras FS, uma vez que estas apresentaram solvente residual no interior da fibra, causando indesejada lise celular. As fibras FD apresentaram resultados de adesão e proliferação adequados para mioblastos, fibroblastos e condrócitos, porém os resultados foram considerados impróprios para hepatócitos. / The lost or failure of an organ or tissue is one of the most severe problems in human health. Tissue engineering, defined as the seeding and adhesion of human cells in vitro over a scaffold, arises as an viable alternative for reproduction of organs and tissues. These cells proliferate, migrate and differentiate into a specific tissue while producing extracellular matrix components. The obtaining of fibrous scaffolds from a polymeric blend of Poly (Lactic-co-Glycolic Acid) (PLGA) and Polyisoprene (PI) is proposed as an alternative to soft tissue engineering. This material was processed as a fibrous structure through dripping (FD) and electrospinning (FS) methods. Physical-chemical characterization was applied to the blend and to the generated fibres. Fibres viability was also observed for murine myoblasts, human dermal fibroblasts, bovine chondrocytes and hepatocellular carcinoma cultures. It was noticed that the blending process didn't have any influence over polymer's chemical structure, being observed the immiscibility between the raw materials. Blend's ductile behaviour was pointed out as an effect of PI presence, although this mixture presents similar wettability to the one presented by these raw polymers. Fibres obtained by electrospinnig generated a scaffold with smaller porosity, even presenting fibres with smaller diameter and a parallel organized topography. The fibres obtained by dripping presented a tangled structure of thicker fibres, but assembling a scaffold with higher porosity and inner space. Mechanical properties of both scaffolds indicate their applicability as soft tissue substitutes. Cell viability assays condemn the use of FS fibres, seen that they present residual solvent trapped into the fibre, causing undesirable cell lysis. On the other hand, FD fibres presented positive adhesion and proliferation results for myoblasts, fibroblasts and chondrocytes cell lines, however the results were consider inappropriate for hepatocytes.

Thèse réalisée dans le cadre d'une collaboration avec UCB Pharma et la région Wallonne s'inscrivant dans le cadre du projet SAS. Le but de ce projet était de développer des implants sous-cutanés imprimés en trois dimensions pour permettre une libération d’anticorps thérapeutique de manière prolongée au cours du temps. En effet, les thérapies disponibles sont souvent administrées par voie intraveineuse, ce qui peut réduire la compliance des patients dû à l’inconfort et à la fréquence de ces administrations. Les systèmes de délivrance, tels que des implants, peuvent limiter les fréquences d’administration grâce à l’insertion d’un dispositif qui libèrera le principe actif au cours du temps durant une période donnée. Les implants s’inscrivent comme une alternative aux microsphères qui sont également des dispositifs développés et investigués en vue de favoriser l’adhésion et la compliance des patients. L’avènement du 3D dans le milieu pharmaceutique a montré une certaine frénésie liée au développement de la médecine personnalisée et à l’innovation du procédé dans ce secteur. La sélection d’un matériau biocompatible et biorésorbable tel que le PLGA représente une véritable plus-value dans le développement d’implant. Etant donné que ces implants sont biodégradables, le retrait n’est pas à envisager, ce qui limite les désagréments du patient à un seul acte chirurgical lors de l’implantation. Au cours de ce travail, une approche pragmatique a d’abord été abordée sur les procédés d’extrusion à chaud et de l’impression 3D en utilisant un polymère couramment employé dans l’impression grand public, le PLA. L’investigation des paramètres d’impressions (température d’impression, epaisseur de couche et vitesse d’impression) et l’usage de divers plastifiants (la triacétine (TA), le polyethylène glycol 400 (PEG 400), le citrate de triéthyle (TEC) et l’acétyle citrate de triéthyle (ATEC)) pour faciliter les procédés à chaud et dans l’idée de réduire les températures d’extrusion et d’impression du matériau ont été évalués. Ces essais ont démontré l’effet de la température d’impression sur la qualité de l’impression et principalement sur les propriétés du matériau comme la force de traction et la ductilité. De plus, l’ajout de plastifiant à la matrice du PLA a permis de diminuer sa température de transition vitreuse. Par exemple, la température de transition vitreuse du PLA a été diminuée de 53 °C à 34 °C par l’ajout de PEG 400. Cette approche avait pour but d’évaluer la possibilité de diminuer les températures d’impression dans l’optique d’encapsuler à chaud un anticorps sensible à la chaleur pour la suite de ce travail.Ensuite, le développement de filaments imprimables contenant des anticorps a été abordé et mis en place à l’aide d’un modèle d’anticorps polyclonal disponible en grandes quantités et à des coûts relativement faibles. Un anticorps à l’état solide a été favorisé dans le procédé car il est largement accepté que les protéines sous forme solide sont plus stables au cours du temps en comparaison aux solutions d’anticorps. De plus, cet état solide facilite les manipulations précédant l’extrusion comme l’étape de mélange. Pour la réalisation des filaments, différents types de PLGA ont été investigués afin d’atteindre les propriétés nécessaires à l’impression en termes de diamètre mais également de comportement physique. Ces dérivés étaient caractérisés par des masses moléculaires différentes comme pour le PDLG5004 (44 kDa), le RG502 (7-17 kDa) et parmis eux, un copolymère PEG-PLGA (2 kDa-20 kDa). Un PLGA de faible masse moléculaire a été sélectionné pour développer ce filament. En effet, les extrusions étaient réalisables à une température maximum de 90 °C et les impressions à 113 °C minimum. L’un des enjeux cruciaux du développement de filament imprimable contenant un anticorps à haute concentration, au minimum 15% (w/w), était d’en assurer l’homogénéité. Cependant, l’usage de températures aussi élevées lors de l’impression a induit la dégradation de l’anticorps par la formation d’agrégats et principalement de fragments. Ces derniers sont généralement produits lors de procédé à haute température ou par l’usage de conditions drastiques telles que l’acidification du milieu. Cette plateforme a été adaptée à l’encapsulation d’anticorps thérapeutique fournit par UCB Pharma. L’usage d’un anticorps monoclonal possédant une stabilité supérieure à celle du modèle initialement utilisé permettrait d’identifier l’impact du procédé sur l’intégrité de l’anticorps. La formulation de l’anticorps a été réalisée en utilisant différents stabilisants conventionnels (sucrose (Suc), trehalose (Tre), 2-Hydroxypropyl-beta-cyclodextrine (HP-β-CD), inuline (Inu) et sorbitol (Sor)) et reconnus pour la stabilisation des protéines. A côté des excipients ajoutés, différentes quantités d’excipients ont été investigués. Ces manipulations ont montré que la stabilité de l’anticorps était privilégiée à l’aide du sucrose et du tréhalose à un ratio anticorps monoclonal:excipient de 2.0:1. En gardant ce ratio, l’ajout d’un acide aminé (leucine) aux deux disaccharides précédemment cités, a amélioré la stabilité de l’anticorps vis-à-vis des procédés à chaud (extrusion et impression 3D). L’homogénéité au sein des filaments imprimables et des pièces 3D a été confirmée tout au long du procédé. En effet, les charges en anticorps étaient similaires à la charge théorique de 15% (w/w). Aucune fragmentation de l’anticorps n’a été observée à l’issue des procédés à chaud. Cependant, une augmentation des agrégats de 2.6% en solution à 3.6% après impression 3D a été constatée à la fin du processus. Après avoir stabilisé l’anticorps, le but premier étant d’en promouvoir une libération prolongée au cours du temps. Les profils ont révélé une libération en trois phases au cours du temps mais avec un relargage après 24h relativement faible (< 5%) dû à la densité des matrices polymériques. Ensuite, la dégradation du polymère représente l’élément limitant la libération de l’anticorps au cours du temps. En effet, l’érosion du polymère joue un rôle clé dans la libération de l’anticorps encapsulé. La libération au cours du temps a été démontrée sur une période allant jusqu’à 15 semaines. La stabilité de l’anticorps dans le milieu de dissolution a été évaluée et une dégradation de celui-ci au cours du temps a été observée. Cette dégradation est principalement liée à l’érosion du polymère et à l’acidification du milieu au cours du test de dissolution. Après avoir optimisé la formulation de l’anticorps et avoir démontré la libération prolongée de celui-ci, son affinité restait à être étudiée. La capacité de l’anticorps à se lier à sa cible a pu être démontrée après 24h de dissolution mais cette affinité s’est réduite au cours de la durée de la dissolution avec une augmentation de l’agrégation et de la fragmentation de l’anticorps. Une étude de stabilité a également démontré que les implants imprimés en 3D sont stables à une température 5 °C sur une durée de 6 mois. Aucun élément de dégradation n’a été observé au cours du temps et l’affinité de l’anticorps a été préservée au cours de l’étude. Finalement, cette plateforme a également été évaluée pour l’encapsulation d’une troisième molécule biologique, un fragment d’anticorps monoclonal, pour d’une part en estimer la stabilité et l’applicabilité et d’autre part envisager une prochaine étude pré-clinique sur rongeurs. Le fragment d’anticorps a montré une stabilité supérieure à celle de l’anticorps monoclonal avec une faible agrégation après l’extrusion et l’impression. La libération prolongée du fragment a été évaluée sur 8 semaines et une libération du fragment de 79% a été observée avec une formulation contenant du tréhalose et de la leucine. En effet, les fragments d’anticorps ont une demi-vie plasmatique relativement faible, de l’ordre de 28 minutes, ce qui donne tout son sens à des systèmes à libération prolongée. Pour finir, la réalisation d’une étude pré-clinique permettrait de valider le modèle. En conclusion, ce travail a démontré la faisabilité de l’usage de l’impression 3D en vue de développer des systèmes à libération prolongée contenant des anticorps et en utilisant des procédés à hautes températures. Ces implants ont été caractérisés par une stabilité favorable et une libération intéressante qui feront l’objet d’investigation lors d’études pharmacocinétiques. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished

No description available.

Capsaicin, prostaglandin E2 (PGE2) and polydopamine (PDA) were used to target macrophage and myofibroblast activity to reduce biomaterial-induced fibrosis. The lifetime and efficacy of implantable biomedical devices are determined by the foreign body response. Immediately after implantation, proteins nonspecifically adsorb onto the material and initiate inflammation. Macrophages recruited to the site can differentiate into M1 and M2 phenotypes and upregulate inflammation and fibrosis which interferes with the intended function. M1 macrophages secrete pro-inflammatory mediators that induce chronic inflammation and promote myofibroblast differentiation while M2 macrophages are wound healing cells that suppress inflammation and regulate fibroblast activity. The fibrotic tissue is developed by myofibroblasts which produce collagen in an unregulated fashion. Collagen thickening and biomaterial encapsulation decreases efficacy and sensitive of biomedical devices. We investigated the in vitro and in vivo effects of capsaicin, PGE2 and polydopamine surface modification on macrophages and myofibroblasts. Capsaicin and PGE2 reduced poly(lactic-co-glycolic) acid (PLGA)-induced fibrosis by promoting M2 macrophage phenotype to secrete anti-inflammatory IL-10 and suppressing myofibroblast marker α-smooth muscle actin (α-SMA). Capsaicin decreased collagen by 40% and upregulated IL-10 secretion by 35% while PGE2 reduced collagen by 55% after 14 days of implantation and 40% less collagen after 42 days. PDA was used to bind an anti-fibrotic compound to the surface of a poly(dimethyl siloxane) (PDMS-PDA) to reduce fibrosis. However, PDMS-PDA controls gave an unexpected result by reducing fibrosis to the same extent as anti-fibrotic compound bound PDMS- v PDA. PDA modification reduced cellularity by 50% and significantly decreased collagen thickness by 30%. Overall, our results showed that biomaterial-induced fibrosis can be reduced by promoting M2 macrophage activity and inhibiting myofibroblast differentiation. This research demonstrates three compounds that have potential to reduce fibrosis and extend the lifetime and efficacy of implantable biomedical devices. / Thesis / Master of Applied Science (MASc) / Capsaicin, prostaglandin E2 (PGE2) and polydopamine were used to reduce scar tissue development around implanted polymers. Biomedical devices implanted in the body can undergo severe scar tissue formation, or fibrosis, and fail. Fibrosis is described by the accumulation of collagen and encapsulation of an implanted polymer. Macrophages regulate fibrosis by secreting pro-fibrotic compounds and myofibroblasts produce unregulated amounts of collagen. In this thesis, capsaicin, PGE2 and polydopamine were incorporated into implants to target macrophage and myofibroblast activity and reduce fibrosis in mice. Capsaicin and PGE2, released from a degradable polymer, altered macrophages to secrete anti-fibrotic compounds and decreased collagen by 40% and 55%, respectively. Polydopamine surface modified implants gave an unexpected result and suppressed overall cell activity to reduce fibrosis by 30%. The research conducted shows the potential of these compounds to reduce fibrosis and extend the lifetime of implantable devices.

No description available.