title: Nano-fibrin stabilized CaSO4 crystals incorporated injectable chitin composite hydrogel for enhanced angiogenesis & osteogenesis.
abstract: Calcium sulfate (CaSO4), an excellent biodegradable bone forming agent that is an ideal choice as additive in gels, however, its disadvantage being poor gel rheology and angiogenesis. Here, we have synthesized chitin-CaSO4-nano-fibrin based injectable gel system which shows improved rheology and angiogenic potential. Rheological studies showed that the composite gel was a shear thinning gel with elastic modulus of 15.4±0.275kPa; a 1.67 fold increase over chitin control. SEM and XRD analyses revealed the effect of nano-fibrin (nFibrin) in transforming CaSO4 crystal shape from needle to hexagonal. It also masked the retarding effect of CaSO4 towards in vitro early cell attachment and angiogenesis using rabbit adipose derived mesenchymal stem cells (rASCs) and HUVECs, respectively. rASCs osteogenesis was confirmed by spectrophotometric endpoint assay, which showed 6-fold early increase in alkaline phosphatase levels and immuno-cytochemistry analysis. These in vitro results highlight the potential of injectable chitin-CaSO4-nFibrin gel for osteo-regeneration via enhanced angiogenesis.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, Kerala, India.
authors.forename: R
authors.initials: R
authors.lastname: Arun Kumar
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, Kerala, India.
authors.forename: A
authors.initials: A
authors.lastname: Sivashanmugam
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Deepthi
authors.affiliation: Biomedical Engineering Department, University of Memphis, Joint University of Memphis-University of Tennessee Graduate Biomedical Engineering Program, Memphis, TN, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Bumgardner
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, Kerala, India.
authors.forename: Shantikumar V
authors.initials: SV
authors.lastname: Nair
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, Kerala, India. Electronic address: rjayakumar@aims.amrita.edu.
authors.forename: R
authors.initials: R
authors.lastname: Jayakumar
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D002133:Calcium Sulfate / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002686:Chitin / Q000737:chemistry*; D004355:Drug Stability; D004548:Elasticity; D005337:Fibrin / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000494:pharmacology*; D007267:Injections; D049329:Nanostructures / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D013314:Stress, Mechanical; D013696:Temperature; D014783:Viscosity
chemical_list: D001672:Biocompatible Materials; D002686:Chitin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005337:Fibrin; D002133:Calcium Sulfate
keywords: Angiogenesis; Bone regeneration; Calcium sulfate; Fibrin nanoparticles; Injectable chitin gel; Osteo differentiation