Tissue adhesive FK506–loaded polymeric nanoparticles for multi–layered nano–shielding of pancreatic islets to enhance xenograft survival in a diabetic mouse model

Autor: Hanh Thuy Nguyen, Tiep Tien Nguyen, Jong Oh Kim, Simmyung Yook, Pil Hoon Park, Tuan Hiep Tran, Cheol Hee Ahn, Shobha Regmi, Chul Soon Yong, Young Kyung Bae, Shiva Pathak, Youngro Byun, Min Hui Park, Tung Thanh Pham, Jee-Heon Jeong, Jeong Uk Choi
Rok vydání: 2018
Předmět:
Male
Polymers
medicine.medical_treatment
02 engineering and technology
01 natural sciences
Regenerative medicine
Polyethylene Glycols
Rats
Sprague-Dawley
chemistry.chemical_compound
Coated Materials
Biocompatible
Polylactic Acid-Polyglycolic Acid Copolymer
geography.geographical_feature_category
Graft Survival
Biomaterial
021001 nanoscience & nanotechnology
Islet
Dihydroxyphenylalanine
medicine.anatomical_structure
Mechanics of Materials
Heterografts
Collagen
0210 nano-technology
Materials science
Transplantation
Heterologous
Biophysics
Bioengineering
010402 general chemistry
Tacrolimus
Diabetes Mellitus
Experimental
Biomaterials
Islets of Langerhans
Antigen
medicine
Animals
Lactic Acid
Tissue Survival
geography
Islet cell transplantation
Pancreatic islets
technology
industry
and agriculture
0104 chemical sciences
Mice
Inbred C57BL
Disease Models
Animal
chemistry
Ceramics and Composites
Nanoparticles
Surface modification
Tissue Adhesives
Ethylene glycol
Polyglycolic Acid
Biomedical engineering
Zdroj: Biomaterials. 154:182-196
ISSN: 0142-9612
Popis: This study aims to develop a novel surface modification technology to prolong the survival time of pancreatic islets in a xenogenic transplantation model, using 3,4-dihydroxyphenethylamine (DOPA) conjugated poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (DOPA-NPs) carrying immunosuppressant FK506 (FK506/DOPA-NPs). The functionalized DOPA-NPs formed a versatile coating layer for antigen camouflage without interfering the viability and functionality of islets. The coating layer effectively preserved the morphology and viability of islets in a co-culture condition with xenogenic lymphocytes for 7 days. Interestingly, the mean survival time of islets coated with FK506/DOPA-NPs was significantly higher as compared with that of islets coated with DOPA-NPs (without FK506) and control. This study demonstrated that the combination of surface camouflage and localized low dose of immunosuppressant could be an effective approach in prolonging the survival of transplanted islets. This newly developed platform might be useful for immobilizing various types of small molecules on therapeutic cells and biomaterial surface to improve the therapeutic efficacy in cell therapy and regenerative medicine.
Databáze: OpenAIRE
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