title: Osteoid-mimicking dense collagen/chitosan hybrid gels.
abstract: Bone extracellular matrix (ECM) is a 3D network, composed of collagen type I and a number of other macromolecules, including glycosaminoglycans (GAGs), which stimulate signaling pathways that regulate osteoblast growth and differentiation. To model the ECM of bone for tissue regenerative approaches, dense collagen/chitosan (Coll/CTS) hybrid hydrogels were developed using different proportions of CTS to mimic GAG components of the ECM. MC3T3-E1 mouse calvaria preosteoblasts were seeded within plastically compressed Coll/CTS hydrogels with solid content approaching that of native bone osteoid. Dense, cellular Coll/CTS hybrids were maintained for up to 8 weeks under either basal or osteogenic conditions. Higher CTS content significantly increased gel resistance to collagenase degradation. The incorporation of CTS to collagen gels decreased the apparent tensile modulus from 1.82 to 0.33 MPa. In contrast, the compressive modulus of Coll/CTS hybrids increased in direct proportion to CTS content exhibiting an increase from 23.50 to 55.25 kPa. CTS incorporation also led to an increase in scaffold resistance to cell-induced contraction. MC3T3-E1 viability, proliferation, and matrix remodeling capability (via matrix metalloproteinase expression) were maintained. Alkaline phosphatase activity was increased up to two-fold, and quantification of phosphate mineral deposition was significantly increased with CTS incorporation. Thus, dense Coll/CTS scaffolds provide osteoid-like models for the study of osteoblast differentiation and bone tissue engineering.
authors.affiliation: Department of Mining and Materials Engineering, Faculty of Engineering, McGill University, Montreal, Quebec, Canada H3A 2B2.
authors.forename: Florencia
authors.initials: F
authors.lastname: Chicatun
authors.forename: Claudio E
authors.initials: CE
authors.lastname: Pedraza
authors.forename: Chiara E
authors.initials: CE
authors.lastname: Ghezzi
authors.forename: Benedetto
authors.initials: B
authors.lastname: Marelli
authors.forename: Mari T
authors.initials: MT
authors.lastname: Kaartinen
authors.forename: Marc D
authors.initials: MD
authors.lastname: McKee
authors.forename: Showan N
authors.initials: SN
authors.lastname: Nazhat
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D048271:Chitosan / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D020100:Hydrogels; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010006:Osteoblasts / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D020100:Hydrogels; D003094:Collagen; D048271:Chitosan; D000469:Alkaline Phosphatase; D053509:Matrix Metalloproteinase 13