title: Biocomposite macroporous cryogels as potential carrier scaffolds for bone active agents augmenting bone regeneration.
abstract: Osteoinduction can be enhanced by combining scaffolds with bone morphogenic protein-2 (BMP-2). However, BMP's are known to also cause bone resorption. This can be controlled using bisphosphonates like zoledronic acid (ZA). In this study, we produced two different scaffolds containing silk-fibroin, chitosan, agarose and hydroxyapatite (HA) with and without bioactive glass. The aims of the study were to fabricate, physico-chemically characterize and evaluate the carrier properties of the scaffolds for recombinant human BMP-2 (rhBMP-2) and ZA. Scaffolds were characterized using various methods to confirm their composition. During cell-material interactions, both scaffolds exhibited gradual but sustained proliferation of both C2C12 and MSCs for a period of 6weeks with augmentative effects on their phenotype indicated by elevated levels of alkaline phosphatase (ALP) cuing towards osteogenic differentiation. In-vitro effects of rhBMP-2 and ZA contained within both the scaffolds was assessed on MC3T3 preosteoblast cells and the results show a significant increase in the ALP activity of the cells seeded on scaffolds with rhBMP-2. Further, the scaffold with both HA and bioactive glass was considered for the animal study. In-vitro, this scaffold released nearly 25% rhBMP-2 in 21-days and the addition of ZA did not affect the release. In the animal study, the scaffolds were combined with rhBMP-2 and ZA, rhBMP-2 or implanted alone in an ectopic muscle pouch model. Significantly higher bone formation was observed in the scaffold loaded with both rhBMP-2 and ZA as seen from micro-computed tomography, histomorphometry and energy dispersive X-ray spectroscopy.
authors.affiliation: Department of Biological Sciences and Bioengineering, Center for Environmental Sciences and Engineering, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India; Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund 221 85, Sweden.
authors.forename: Deepak Bushan
authors.initials: DB
authors.lastname: Raina
authors.affiliation: Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund 221 85, Sweden; Department of Biomedical Engineering, Lund University, Lund 221 00, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Isaksson
authors.affiliation: Department of Biological Sciences and Bioengineering, Center for Environmental Sciences and Engineering, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India.
authors.forename: Arun Kumar
authors.initials: AK
authors.lastname: Teotia
authors.affiliation: Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund 221 85, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lidgren
authors.affiliation: Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund 221 85, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Tägil
authors.affiliation: Department of Biological Sciences and Bioengineering, Center for Environmental Sciences and Engineering, Indian Institute of Technology Kanpur, Kanpur 208016, UP, India. Electronic address: ashokkum@iitk.ac.in.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry; D001861:Bone Regeneration; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D059985:Cryogels / Q000008:administration & dosage* / Q000737:chemistry; D004164:Diphosphonates / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry; D005349:Fibroins / Q000737:chemistry; D005898:Glass / Q000737:chemistry; D007093:Imidazoles / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D012685:Sepharose / Q000737:chemistry; D000077211:Zoledronic Acid
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D059985:Cryogels; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D011994:Recombinant Proteins; D000077211:Zoledronic Acid; D005349:Fibroins; D012685:Sepharose; D048271:Chitosan; D017886:Durapatite; D000469:Alkaline Phosphatase
keywords: Biocomposite; Biomaterial; Bone tissue engineering; Cryogel; Zoledronic acid