Object To evaluate iodine-containing polyvinyl alcohol (I-PVA) as a precipitating liquid embolic ... more Object To evaluate iodine-containing polyvinyl alcohol (I-PVA) as a precipitating liquid embolic agent, implant characteristics—including radiopacity, setting behavior, and biocompatibility—were studied in an aneurysm model in swine. Methods Twelve broad-based carotid artery (CA) sidewall aneurysms were surgically constructed in six pigs. Iodine-containing polyvinyl alcohol dissolved in dimethyl sulfoxide (DMSO) was injected during temporary balloon occlusion bridging the aneurysm neck. Control angiography as well as multidetector row computerized tomography (CT) angiography was performed after 4 weeks. Harvested aneurysms were investigated histopathologically and by 3-tesla high-field magnetic resonance (MR) imaging. The mean degree of aneurysm occlusion achieved was 96%. In two aneurysms a minimal protrusion of I-PVA into the CA lumen was observed. During one embolization, leakage of the liquid embolic agent due to DMSO-induced damage of the microcatheter resulted in CA occlusion. Aneurysms embolized with I-PVA could be discriminated clearly from the parent artery on CT angiograms because there was no beam-hardening artifact. High-field MR imaging allowed a detailed depiction of the liquid embolic distribution within the aneurysm. Histologically, a mild to moderate inflammatory response was found in successfully embolized aneurysms, and the polymer mass was frequently covered by a membrane of fibroblasts and endothelial cells. Conclusions Iodine-containing polyvinyl alcohol is a ready-to-use liquid embolic agent clearly visible under fluoroscopy; additives are not required. The setting behavior allows for controlled delivery in aneurysm cavities. Histological studies performed 4 weeks after embolization revealed no sign of toxic tissue response to the liquid embolic agent. Overall, I-PVA exhibits interesting implant characteristics in that radiopaque admixtures are not necessary, thus allowing for artifact-free evaluation of treated aneurysms by using CT and MR angiography.
In severe malformations with a lack of native tissues, treatment options are limited. We aimed at... more In severe malformations with a lack of native tissues, treatment options are limited. We aimed at expanding tissue in vivo using the body as a bioreactor and developing a sustainable single-staged procedure for autologous tissue reconstruction in malformation surgery. Autologous micro-epithelium from skin was integrated with plastically compressed collagen and a degradable knitted fabric mesh. Sixty-three scaffolds were implanted in nine rats for histological and mechanical analyses, up to 4 weeks after transplantation. Tissue integration, cell expansion, proliferation, inflammation, strength, and elasticity were evaluated over time in vivo and validated in vitro in a bladder wound healing model. After 5 days in vivo, we observed keratinocyte proliferation on top of the transplant, remodeling of the collagen, and neovascularization within the transplant. At 4 weeks, all transplants were fully integrated with the surrounding tissue. Tensile strength and elasticity were retained durin...
Hyaluronic acid (HA) is extensively used in the design of hydrogels and nanoparticles for differe... more Hyaluronic acid (HA) is extensively used in the design of hydrogels and nanoparticles for different biomedical applications. Here, we critically assessed HA-based hydrogels and nanomaterials that are crosslinked by dynamic-covalent coupling (DCC) chemistry.
Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persis... more Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of main biological processes in fabrication and construction of supramolecular hydrogel networks required for biomedical applications. The enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most of cases, structure and substrates of hydrogels are adjusted by enzyme catalysis due to the chemo-, regio- and stereo-selectivity of enzymes. Hydrogels processed by using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules and drugs in biomedical applications. A novel class of enzyme-mediated crosslinking hydrogels mimics the extracellular matrices by displaying unique physicochemical properties and functionalities like water-retention capacity, drug loading ability, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-heali...
We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation re... more We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation reaction that could be adapted for both aldehyde and keto substrates. We found that saline accelerated ...
There is an unmet need to develop strategies that allow site-specific delivery of short interferi... more There is an unmet need to develop strategies that allow site-specific delivery of short interfering RNA (siRNA) without any associated toxicity. Here we report a modular delivery system that can be custom modified with targeting peptide and siRNAs.
Organoids can shed light on the dynamic interplay between complex tissues and rare cell types wit... more Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we developed gut organoid co-cultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate for the first time that murine and human ILC1 secrete TGFβ1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest th...
Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanic... more Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanics of polymeric materials and impart biological function. As well as their utility as physical cross-linkers, clays have been explored for sustained localization of biomolecules to promote in vivo tissue regeneration. To date, both biomolecule-clay and polymer-clay nanocomposite strategies have utilised the negatively charged clay particle surface. As such, biomolecule-clay and polymer-clay interactions are set in competition, potentially limiting the functional enhancements achieved. Here, we apply specific bisphosphonate interactions with the positively charged clay particle edge to develop self-assembling hydrogels and functionalized clay nanoparticles with preserved surface exchange capacity. Low concentrations of nanoclay are applied to cross-link hyaluronic acid polymers derivatised with a pendant bisphosphonate to generate hydrogels with enhanced mechanical properties and preserved...
Simvastatin delivered using hyaluronan-based nanoparticles suppress drug induced myotoxicity in t... more Simvastatin delivered using hyaluronan-based nanoparticles suppress drug induced myotoxicity in tissue engineered skeletal muscles 3D model.
Biohybrid hydrogels consisting of solubilized nanostructured pericardial matrix and electroconduc... more Biohybrid hydrogels consisting of solubilized nanostructured pericardial matrix and electroconductive positively charged hydrazide-conjugated carbon nanotubes provide a promising material for stem cell-based cardiac tissue engineering.
Simple monovalent and divalent salts are presented as a novel catalyst for performing hydrazone a... more Simple monovalent and divalent salts are presented as a novel catalyst for performing hydrazone and oxime coupling chemistry at physiological pH with excellent yields.
Object To evaluate iodine-containing polyvinyl alcohol (I-PVA) as a precipitating liquid embolic ... more Object To evaluate iodine-containing polyvinyl alcohol (I-PVA) as a precipitating liquid embolic agent, implant characteristics—including radiopacity, setting behavior, and biocompatibility—were studied in an aneurysm model in swine. Methods Twelve broad-based carotid artery (CA) sidewall aneurysms were surgically constructed in six pigs. Iodine-containing polyvinyl alcohol dissolved in dimethyl sulfoxide (DMSO) was injected during temporary balloon occlusion bridging the aneurysm neck. Control angiography as well as multidetector row computerized tomography (CT) angiography was performed after 4 weeks. Harvested aneurysms were investigated histopathologically and by 3-tesla high-field magnetic resonance (MR) imaging. The mean degree of aneurysm occlusion achieved was 96%. In two aneurysms a minimal protrusion of I-PVA into the CA lumen was observed. During one embolization, leakage of the liquid embolic agent due to DMSO-induced damage of the microcatheter resulted in CA occlusion. Aneurysms embolized with I-PVA could be discriminated clearly from the parent artery on CT angiograms because there was no beam-hardening artifact. High-field MR imaging allowed a detailed depiction of the liquid embolic distribution within the aneurysm. Histologically, a mild to moderate inflammatory response was found in successfully embolized aneurysms, and the polymer mass was frequently covered by a membrane of fibroblasts and endothelial cells. Conclusions Iodine-containing polyvinyl alcohol is a ready-to-use liquid embolic agent clearly visible under fluoroscopy; additives are not required. The setting behavior allows for controlled delivery in aneurysm cavities. Histological studies performed 4 weeks after embolization revealed no sign of toxic tissue response to the liquid embolic agent. Overall, I-PVA exhibits interesting implant characteristics in that radiopaque admixtures are not necessary, thus allowing for artifact-free evaluation of treated aneurysms by using CT and MR angiography.
In severe malformations with a lack of native tissues, treatment options are limited. We aimed at... more In severe malformations with a lack of native tissues, treatment options are limited. We aimed at expanding tissue in vivo using the body as a bioreactor and developing a sustainable single-staged procedure for autologous tissue reconstruction in malformation surgery. Autologous micro-epithelium from skin was integrated with plastically compressed collagen and a degradable knitted fabric mesh. Sixty-three scaffolds were implanted in nine rats for histological and mechanical analyses, up to 4 weeks after transplantation. Tissue integration, cell expansion, proliferation, inflammation, strength, and elasticity were evaluated over time in vivo and validated in vitro in a bladder wound healing model. After 5 days in vivo, we observed keratinocyte proliferation on top of the transplant, remodeling of the collagen, and neovascularization within the transplant. At 4 weeks, all transplants were fully integrated with the surrounding tissue. Tensile strength and elasticity were retained durin...
Hyaluronic acid (HA) is extensively used in the design of hydrogels and nanoparticles for differe... more Hyaluronic acid (HA) is extensively used in the design of hydrogels and nanoparticles for different biomedical applications. Here, we critically assessed HA-based hydrogels and nanomaterials that are crosslinked by dynamic-covalent coupling (DCC) chemistry.
Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persis... more Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of main biological processes in fabrication and construction of supramolecular hydrogel networks required for biomedical applications. The enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most of cases, structure and substrates of hydrogels are adjusted by enzyme catalysis due to the chemo-, regio- and stereo-selectivity of enzymes. Hydrogels processed by using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules and drugs in biomedical applications. A novel class of enzyme-mediated crosslinking hydrogels mimics the extracellular matrices by displaying unique physicochemical properties and functionalities like water-retention capacity, drug loading ability, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-heali...
We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation re... more We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation reaction that could be adapted for both aldehyde and keto substrates. We found that saline accelerated ...
There is an unmet need to develop strategies that allow site-specific delivery of short interferi... more There is an unmet need to develop strategies that allow site-specific delivery of short interfering RNA (siRNA) without any associated toxicity. Here we report a modular delivery system that can be custom modified with targeting peptide and siRNAs.
Organoids can shed light on the dynamic interplay between complex tissues and rare cell types wit... more Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we developed gut organoid co-cultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate for the first time that murine and human ILC1 secrete TGFβ1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest th...
Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanic... more Nanoclays have generated interest in biomaterial design for their ability to enhance the mechanics of polymeric materials and impart biological function. As well as their utility as physical cross-linkers, clays have been explored for sustained localization of biomolecules to promote in vivo tissue regeneration. To date, both biomolecule-clay and polymer-clay nanocomposite strategies have utilised the negatively charged clay particle surface. As such, biomolecule-clay and polymer-clay interactions are set in competition, potentially limiting the functional enhancements achieved. Here, we apply specific bisphosphonate interactions with the positively charged clay particle edge to develop self-assembling hydrogels and functionalized clay nanoparticles with preserved surface exchange capacity. Low concentrations of nanoclay are applied to cross-link hyaluronic acid polymers derivatised with a pendant bisphosphonate to generate hydrogels with enhanced mechanical properties and preserved...
Simvastatin delivered using hyaluronan-based nanoparticles suppress drug induced myotoxicity in t... more Simvastatin delivered using hyaluronan-based nanoparticles suppress drug induced myotoxicity in tissue engineered skeletal muscles 3D model.
Biohybrid hydrogels consisting of solubilized nanostructured pericardial matrix and electroconduc... more Biohybrid hydrogels consisting of solubilized nanostructured pericardial matrix and electroconductive positively charged hydrazide-conjugated carbon nanotubes provide a promising material for stem cell-based cardiac tissue engineering.
Simple monovalent and divalent salts are presented as a novel catalyst for performing hydrazone a... more Simple monovalent and divalent salts are presented as a novel catalyst for performing hydrazone and oxime coupling chemistry at physiological pH with excellent yields.
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