Bioconductive 3D nano-composite constructs with tunable elasticity to initiate stem cell growth and induce bone mineralization.
Bioactive 3D composites play an important role in advanced biomaterial design to provide molecular coupling and improve integrity with the cellular environment of the native bone. In the present study, a hybrid lyophilized polymer composite blend of anionic charged sodium salt of carboxymethyl chitin and gelatin (CMChNa-GEL) reinforced with nano-rod agglomerated hydroxyapatite (nHA) has been developed with enhanced biocompatibility and tunable elasticity. The scaffolds have an open, uniform and interconnected porous structure with an average pore diameter of 157±30μm and 89.47+0.03% with four dimensional X-ray. The aspect ratio of ellipsoidal pores decrease from 4.4 to 1.2 with increase in gelatin concentration; and from 2.14 to 1.93 with decrease in gelling temperature. The samples were resilient with elastic stain at 1.2MPa of stress also decreased from 0.33 to 0.23 with increase in gelatin concentration. The crosslinker HMDI (hexamethylene diisocyanate) yielded more resilient samples at 1.2MPa in comparison to glutaraldehyde. Increased crosslinking time from 2 to 4h in continuous compression cycle show no improvement in maximum elastic stain of 1.2MPa stress. This surface elasticity of the scaffold enables the capacity of these materials for adherent self renewal and cultivation of the NTERA-2 cL.D1 (NT2/D1), pluripotent embryonal carcinoma cell with biomechanical surface, as is shown here. Proliferation with MG-63, ALP activity and Alizarin red mineralization assay on optimized scaffold demonstrated ***p<0.001 between different time points thus showing its potential for bone healing. In pre-clinical study histological bone response of the scaffold construct displayed improved activity of bone regeneration in comparison to self healing of control groups (sham) up to week 07 after implantation in rabbit tibia critical-size defect. Therefore, this nHA-CMChNa-GEL scaffold composite exhibits inherent and efficient physicochemical, mechanical and biological characteristics based on gel concentrations, gelatin mixing and gelling temperature thus points to creating bioactive 3D scaffolds with tunable elasticity for orthopedic applications.
Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India.
Nitin
N
Sagar
Centre for Research in Nanotechnology and Science, Indian Institute of Technology-Bombay, Mumbai 400076, India.
Kunal
K
Khanna
National Institute of Research in Reproductive Health, Mumbai 400012, India.
Varda S
VS
Sardesai
Centre for Research in Nanotechnology and Science, Indian Institute of Technology-Bombay, Mumbai 400076, India.
Atul K
AK
Singh
Department of Chemical Engineering, Indian Institute of Technology-Bombay, Mumbai 400076, India.
Mayur
M
Temgire
Department of Chemical Engineering, Indian Institute of Technology-Bombay, Mumbai 400076, India.
Mridula Phukan
MP
Kalita
Department of Chemical Engineering, Indian Institute of Technology-Bombay, Mumbai 400076, India; Krishna Institute of Medical Sciences, Malkapur, Karad 415539, Dist. Satara, Maharashtra, India.
Sachin S
SS
Kadam
Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India.
Vivek P
VP
Soni
National Institute of Research in Reproductive Health, Mumbai 400012, India.
Deepa
D
Bhartiya
Department of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India; Centre for Research in Nanotechnology and Science, Indian Institute of Technology-Bombay, Mumbai 400076, India; Department of Chemical Engineering, Indian Institute of Technology-Bombay, Mumbai 400076, India; Wadhwani Research Center for Bioengineering, Indian Institute of Technology-Bombay, Mumbai 400076, India. Electronic address: jb@iitb.ac.in.
Jayesh R
JR
Bellare
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology; D004548:Elasticity; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018625:Microscopy, Atomic Force; D009113:Muramidase / Q000378:metabolism; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010758:Phosphorus / Q000032:analysis; D016062:Porosity; D011817:Rabbits; D013052:Spectrometry, X-Ray Emission; D013054:Spectrophotometry, Atomic; D017550:Spectroscopy, Fourier Transform Infrared; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*; D014783:Viscosity; D014961:X-Ray Diffraction
D001672:Biocompatible Materials; D010758:Phosphorus; D017886:Durapatite; D000469:Alkaline Phosphatase; D009113:Muramidase; D002118:Calcium