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Xiaolin Zhang,1,2,* Jiankang Song,3,* Alexey Klymov,3,* Yang Zhang,3 Leonie de Boer,1 John A Jansen,3 Jeroen JJP van den Beucken,3 Fang Yang,3 Sebastian AJ Zaat,1,* Sander CG Leeuwenburgh3,* 1Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; 3Department of Biomaterials, Radboud University Medical Centre, Nijmegen, the Netherlands *These authors contributed equally to this work Background: Infections such as biomaterial-associated infection and osteomyelitis are often associated with intracellular survival of bacteria (eg, Staphylococcus aureus). Treatment of these infections remains a major challenge due to the low intracellular efficacy of many antibiotics. Therefore, local delivery systems are urgently required to improve the therapeutic efficacy of antibiotics by enabling their intracellular delivery. Purpose: To assess the potential of gelatin nanospheres as carriers for local delivery of vancomycin into macrophages of zebrafish larvae in vivo and into THP-1-derived macrophages in vitro using fluorescence microscopy. Materials and methods: Fluorescently labeled gelatin nanospheres were prepared and injected into transgenic zebrafish larvae with fluorescent macrophages. Both the biodistribution of gelatin nanospheres in zebrafish larvae and the co-localization of vancomycin-loaded gelatin nanospheres with zebrafish macrophages in vivo and uptake by THP-1-derived macrophages in vitro were studied. In addition, the effect of treatment with vancomycin-loaded gelatin nanospheres on survival of S. aureus-infected zebrafish larvae was investigated. Results: Internalization of vancomycin-loaded gelatin nanospheres by macrophages was observed qualitatively both in vivo and in vitro. Systemically delive

Xiaolin Zhang,1,2,* Jiankang Song,3,* Alexey Klymov,3,* Yang Zhang,3 Leonie de Boer,1 John A Jansen,3 Jeroen JJP van den Beucken,3 Fang Yang,3 Sebastian AJ Zaat,1,* Sander CG Leeuwenburgh3,* 1Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; 3Department of Biomaterials, Radboud University Medical Centre, Nijmegen, the Netherlands *These authors contributed equally to this work Background: Infections such as biomaterial-associated infection and osteomyelitis are often associated with intracellular survival of bacteria (eg, Staphylococcus aureus). Treatment of these infections remains a major challenge due to the low intracellular efficacy of many antibiotics. Therefore, local delivery systems are urgently required to improve the therapeutic efficacy of antibiotics by enabling their intracellular delivery. Purpose: To assess the potential of gelatin nanospheres as carriers for local delivery of vancomycin into macrophages of zebrafish larvae in vivo and into THP-1-derived macrophages in vitro using fluorescence microscopy. Materials and methods: Fluorescently labeled gelatin nanospheres were prepared and injected into transgenic zebrafish larvae with fluorescent macrophages. Both the biodistribution of gelatin nanospheres in zebrafish larvae and the co-localization of vancomycin-loaded gelatin nanospheres with zebrafish macrophages in vivo and uptake by THP-1-derived macrophages in vitro were studied. In addition, the effect of treatment with vancomycin-loaded gelatin nanospheres on survival of S. aureus-infected zebrafish larvae was investigated. Results: Internalization of vancomycin-loaded gelatin nanospheres by macrophages was observed qualitatively both in vivo and in vitro. Systemically delive

Injectable composite colloidal gels are developed for regeneration of osteoporotic bone defects through a bottom-up assembly from bisphosphonate-functionalized gelatin and bioactive glass particles. Upon bisphosphonate functionalization, gelatin nanoparticles show superior adhesion toward bioactive glass particles, resulting in elastic composite gels. By tuning their composition, these composite colloidal gels combine mechanical robustness with self-healing ability. The composite colloidal gels support cell proliferation and differentiation in vitro without requiring any osteogenic supplement. In vivo evaluation of the composite colloidal gels reveals their capacity to support the regeneration of osteoporotic bone defects. Furthermore, the bisphosphonate modification of gelatin induces a therapeutic effect on the peri-implantation region by enhancing the bone density of the osteoporotic bone tissue. Consequently, these composite colloidal gels offer new therapeutic opportunities for treatment of osteoporotic bone defects.

Injectable composite colloidal gels are developed for regeneration of osteoporotic bone defects through a bottom-up assembly from bisphosphonate-functionalized gelatin and bioactive glass particles. Upon bisphosphonate functionalization, gelatin nanoparticles show superior adhesion toward bioactive glass particles, resulting in elastic composite gels. By tuning their composition, these composite colloidal gels combine mechanical robustness with self-healing ability. The composite colloidal gels support cell proliferation and differentiation in vitro without requiring any osteogenic supplement. In vivo evaluation of the composite colloidal gels reveals their capacity to support the regeneration of osteoporotic bone defects. Furthermore, the bisphosphonate modification of gelatin induces a therapeutic effect on the peri-implantation region by enhancing the bone density of the osteoporotic bone tissue. Consequently, these composite colloidal gels offer new therapeutic opportunities for treatment of osteoporotic bone defects.

Producción Científica, In the field of tissue engineering, the properties of the scaffolds are of crucial importance for the success of the application. Hybrid materials combine properties of the different components that constitute them. In this study hybrid gels of elastin-like recombinamer (ELR) and fibrin were prepared with a range on polymer concentrations and ELR-to-fibrin ratios. The correlation between SEM micrographs, porosity, swelling ratio and rheological properties was discussed and a poroelastic mechanism was suggested to explain the mechanical behavior of the hybrid gels. Applicability as scaffold material for cardiovascular tissue engineering was shown by the realization of cell-laden matrixes which supported the synthesis of collagens as revealed by immunohistochemical analysis. As a proof of concept, a tissue-engineered heart valve was fabricated by injection moulding and cultivated in a bioreactor for 3 weeks under dynamic conditions. Tissue analysis revealed production of collagen I and III, fundamental proteins for cardiovascular constructs., Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA244U13)

Producción Científica, In the field of tissue engineering, the properties of the scaffolds are of crucial importance for the success of the application. Hybrid materials combine properties of the different components that constitute them. In this study hybrid gels of elastin-like recombinamer (ELR) and fibrin were prepared with a range on polymer concentrations and ELR-to-fibrin ratios. The correlation between SEM micrographs, porosity, swelling ratio and rheological properties was discussed and a poroelastic mechanism was suggested to explain the mechanical behavior of the hybrid gels. Applicability as scaffold material for cardiovascular tissue engineering was shown by the realization of cell-laden matrixes which supported the synthesis of collagens as revealed by immunohistochemical analysis. As a proof of concept, a tissue-engineered heart valve was fabricated by injection moulding and cultivated in a bioreactor for 3 weeks under dynamic conditions. Tissue analysis revealed production of collagen I and III, fundamental proteins for cardiovascular constructs., Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA244U13)

Producción Científica, In the field of tissue engineering, the properties of the scaffolds are of crucial importance for the success of the application. Hybrid materials combine properties of the different components that constitute them. In this study hybrid gels of elastin-like recombinamer (ELR) and fibrin were prepared with a range on polymer concentrations and ELR-to-fibrin ratios. The correlation between SEM micrographs, porosity, swelling ratio and rheological properties was discussed and a poroelastic mechanism was suggested to explain the mechanical behavior of the hybrid gels. Applicability as scaffold material for cardiovascular tissue engineering was shown by the realization of cell-laden matrixes which supported the synthesis of collagens as revealed by immunohistochemical analysis. As a proof of concept, a tissue-engineered heart valve was fabricated by injection moulding and cultivated in a bioreactor for 3 weeks under dynamic conditions. Tissue analysis revealed production of collagen I and III, fundamental proteins for cardiovascular constructs., Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA244U13)