title: Alginate Bead Based Hexagonal Close Packed 3D Implant for Bone Tissue Engineering.
abstract: Success of bone tissue engineering (BTE) relies on the osteogenic microarchitecture of the biopolymeric scaffold and appropriate spatiotemporal distribution of therapeutic molecules (growth factors and drugs) inside it. However, the existing technologies have failed to address both the issues together. Keeping this perspective in mind, we have developed a novel three-dimensional (3D) implant prototype by stacking hexagonal close packed (HCP) layers of calcium alginate beads. The HCP arrangement of the beads lead to a patterned array of interconnected tetrahedral and octahedral pores of average diameter of 142.9 and 262.9 μm, respectively, inside the implant. The swelling pattern of the implants changed from isotropic to anisotropic in the z-direction in the absence of bivalent calcium ions (Ca2+) in the swelling buffer. Incubation of the implant in simulated body fluid (SBF) resulted in a 2.7-fold increase in the compressive modulus. The variation in the relaxation times as derived from the Weichert viscoelasticity model predicted a gradual increase in the interactions among the alginate molecules in the matrix. We demonstrated the tunability of the spatiotemporal drug release from the implant in a tissue mimicking porous semisolid matrix as well as in conventional drug release set up by changing the spatial coordinates of the "drug loaded depot layer" inside the implant. The therapeutic potential of the implant was confirmed against Escherichia coli using metronidazole as the model drug. Detailed analysis of cell viability, cell cycle progression, and cytoskeletal reorganization using osteoblast cells (MG-63) proved the osteoconductive nature of the implant. Expression of differentiation markers such as alkaline phosphatase, runx2, and collagen type 1 in human mesenchymal stem cell in vitro confirmed the osteogenic nature of the implant. When tested in vivo, VEGF loaded implant was found capable of inducing angiogenesis in a mice model. In conclusion, the bead based implant may find its utility in non-load-bearing BTE.
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela, Odisha 769008, India.|Department of Biotechnology, Indian Institute of Technology , Kharagpur, West Bengal 721302, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Agarwal
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela, Odisha 769008, India.
authors.forename: Prajna
authors.initials: P
authors.lastname: Kabiraj
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela, Odisha 769008, India.
authors.forename: Gautham Hari
authors.initials: GH
authors.lastname: Narayana
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela, Odisha 769008, India.
authors.forename: Senthilguru
authors.initials: S
authors.lastname: Kulanthaivel
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela, Odisha 769008, India.
authors.forename: Uvanesh
authors.initials: U
authors.lastname: Kasiviswanathan
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela, Odisha 769008, India.
authors.forename: Kunal
authors.initials: K
authors.lastname: Pal
authors.affiliation: Department of Chemistry, National Institute of Technology , Rourkela, Odisha 769008, India.
authors.forename: Supratim
authors.initials: S
authors.lastname: Giri
authors.affiliation: Department of Biotechnology, Indian Institute of Technology , Kharagpur, West Bengal 721302, India.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Maiti
authors.affiliation: Department of Biotechnology and Medical Engineering, National Institute of Technology , Rourkela, Odisha 769008, India.
authors.forename: Indranil
authors.initials: I
authors.lastname: Banerjee
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002454:Cell Differentiation; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells; D051379:Mice; D010012:Osteogenesis; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid
keywords: angiogenesis; beads; bone; calcium alginate; drug delivery; implant; micropatterned; tissue engineering