Browsing by Author "Detamore, MS"

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    Material characterization of microsphere-based scaffolds with encapsulated raw materials
    (MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, 2016) Sridharan, B; Mohan, N; Berkland, CJ; Detamore, MS
    Raw materials, or materials capable of serving both as building blocks and as signals, which are often but not always natural materials, are taking center stage in biomaterials for contemporary regenerative medicine. In osteochondral tissue engineering, a field leveraging the underlying bone to facilitate cartilage regeneration, common raw materials include chondroitin sulfate (CS) for cartilage and p-tricalcium phosphate (TCP) for bone. Building on our previous work with gradient scaffolds based on microspheres, here we delved deeper into the characterization of individual components. In the current study, the release of CS and TCP from poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds was evaluated over a time period of 4 weeks. Raw material encapsulated groups were compared to 'blank' groups and evaluated for surface topology, molecular weight, and mechanical performance as a function of time. The CS group may have led to increased surface porosity, and the addition of CS improved the mechanical performance of the scaffold. The finding that CS was completely released into the surrounding media by 4 weeks has a significant impact on future in vivo studies, given rapid bioavailability. The addition of TCP seemed to contribute to the rough external appearance of the scaffold. The current study provides an introduction to degradation patterns of homogenous raw material encapsulated scaffolds, providing characterization data to advance the field of microsphere-based scaffolds in tissue engineering. (C) 2016 Elsevier B.V. All rights reserved.
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    Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep
    (REGENERATIVE MEDICINE, 2015) Mohan, N; Gupta, V; Sridharan, BP; Mellott, AJ; Easley, JT; Palmer, RH; Galbraith, RA; Key, VH; Berkland, CJ; Detamore, MS
    Background: The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage. Aim: The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs. Materials & methods: The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and beta-tricalcium phosphate. A 1-year repair study in sheep was conducted. Results: The repair tissues in the microfracture were mostly fibrous and had scattered fissures with degenerative changes. Cartilage regenerated with the gradient plugs had equal or superior mechanical properties; had lacunated cells and stable matrix as in hyaline cartilage. Conclusion: This first report of gradient scaffolds in a long-term, large animal, osteochondral defect demonstrated potential for equal or better cartilage repair than microfracture.
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    The potential of encapsulating “raw materials” in 3D osteochondral gradient scaffolds.
    (Biotechnology Bioengineering. 2013,, 2013-12) Mohan, N; Gupta, V; Sridharan, BP; Sutherland, A; Detamore, MS
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    The Potential of Encapsulating "Raw Materials'' in 3D Osteochondral Gradient Scaffolds
    (BIOTECHNOLOGY AND BIOENGINEERING, 2014) Mohan, N; Gupta, V; Sridharan, B; Sutherland, A; Detamore, MS
    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)-3 or bone morphogenetic protein (BMP)-2. It was also noteworthy that a combination of both CS and TGF-3 increased the secretion of collagen type II. Moreover, cells seeded in scaffolds containing opposing gradients of CS/TGF-3 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. Biotechnol. Bioeng. 2014;111: 829-841. (c) 2013 Wiley Periodicals, Inc.