title: The potential of encapsulating "raw materials" in 3D osteochondral gradient scaffolds.
abstract: Scaffolds with continuous gradients in material composition and bioactive signals enable a smooth transition of properties at the interface. Components like chondroitin sulfate (CS) and bioactive glass (BG) in 3D scaffolds may serve as "raw materials" for synthesis of new extracellular matrix (ECM), and may have the potential to completely or partially replace expensive growth factors. We hypothesized that scaffolds with gradients of ECM components would enable superior performance of engineered constructs. Raw material encapsulation altered the appearance, structure, porosity, and degradation of the scaffolds. They allowed the scaffolds to better retain their 3D structure during culture and provided a buffering effect to the cells in culture. Following seeding of rat mesenchymal stem cells, there were several instances where glycosaminoglycan (GAG), collagen, or calcium contents were higher with the scaffolds containing raw materials (CS or BG) than with those containing transforming growth factor (TGF)-β3 or bone morphogenetic protein (BMP)-2. It was also noteworthy that a combination of both CS and TGF-β3 increased the secretion of collagen type II. Moreover, cells seeded in scaffolds containing opposing gradients of CS/TGF-β3 and BG/BMP-2 produced clear regional variations in the secretion of tissue-specific ECM. The study demonstrated raw materials have the potential to create a favorable microenvironment for cells; they can significantly enhance the synthesis of certain extracellular matrix (ECM) components when compared to expensive growth factors; either alone or in combination with growth factors they can enhance the secretion of tissue specific matrix proteins. Raw materials are promising candidates that can be used to either replace or be used in combination with growth factors. Success with raw materials in lieu of growth factors could have profound implications in terms of lower cost and faster regulatory approval for more rapid translation of regenerative medicine products to the clinic.
authors.affiliation: Division of Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
authors.forename: Neethu
authors.initials: N
authors.lastname: Mohan
authors.forename: Vineet
authors.initials: V
authors.lastname: Gupta
authors.forename: Banupriya
authors.initials: B
authors.lastname: Sridharan
authors.forename: Amanda
authors.initials: A
authors.lastname: Sutherland
authors.forename: Michael S
authors.initials: MS
authors.lastname: Detamore
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D001861:Bone Regeneration; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology; D002809:Chondroitin Sulfates / Q000493:pharmacokinetics*; D004337:Drug Carriers; D008422:Materials Testing; D008863:Microspheres; D051381:Rats; D013234:Stem Cells; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds
chemical_list: D004337:Drug Carriers; D002809:Chondroitin Sulfates
keywords: chondroitin sulfate; gradients in signals; microsphere-based scaffold; osteochondral tissue engineering; raw materials