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Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the inflammatory-mediated response associated with fracture repair in vitro and ex vivo injection delivery

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Abstract

A clinical need continues for consistent bone remodeling within problematic sites such as those of fracture nonunion, avascular necrosis, or irregular bone formations. In attempt to address such needs, a biomaterial system is proposed to induce early inflammatory responses after implantation and to provide later osteoconductive scaffolding for bone regeneration. Biomaterial-induced inflammation would parallel the early stage of hematoma-induced fracture repair and allow scaffold-promoted remodeling of osseous tissue to a healthy state. Initiation of the wound healing cascade by two human concentrated platelet releasate-containing alginate/β-tricalcium phosphate biocomposites has been studied in vitro using the TIB-71™ RAW264.7 mouse monocyte cell line. Inflammatory responses inherent to the base material were found and could be modulated through incorporation of platelet releasate. Differences in hydrogel wt% (2 vs. 8 %) and/or calcium phosphate granule vol.% (20 vs. 10 %) allowed for tuning the response associated with platelet releasate-associated growth factor elution. Tunability from completely suppressing the inflammatory response to augmenting the response was observed through varied elution profiles of both releasate-derived bioagents and impurities inherent to alginate. A 2.5-fold upregulation of inducible-nitric oxide synthase gene expression followed by a tenfold increase in nitrite media levels was induced by inclusion of releasate within the 8 wt%/10 vol.% formulation and was comparable to an endotoxin positive control. Whereas, near complete elimination of inflammation was seen when releasate was included within the 2 wt%/20 vol.% formulation. These in vitro results suggested tunable interactions between the multiple platelet releasate-derived bioagents and the biocomposites for enhancing hematoma-like fracture repair. Additionally, minimally invasive delivery for in situ curing of the implant system via injection was demonstrated in rat tail vertebrae using microcomputed tomography.

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Acknowledgments

The authors would like to acknowledge Dr. Thomas Sutter and Quynh Tran from the W. Harry Feinstone Center for Genomic Research for use of the iCycler and discussions on qRT-PCR data analysis. We also thank Dr. Richard A. Smith, Dr. Jinsong Huang, and Dr. Anobel Maghsoodpour for help in capturing data and software analysis pertaining to μCT. We also recognize Dr. John L. Williams from The University of Memphis for participation in the first author’s doctoral advisory committee and review of the current work.

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Authors and Affiliations

  1. Biomedical Engineering Department, Herff College of Engineering, The University of Memphis, 330 Engineering Technology Building, 3815 Central Ave., Memphis, TN, 38152, USA

    Jonathan D. McCanless, Joel D. Bumgardner & Warren O. Haggard

  2. Department of Internal Medicine, College of Medicine, The University of Tennessee Health Science Center, Coleman Building Suite D334, 956 Court Ave., Memphis, TN, 38163, USA

    Lisa K. Jennings

  3. Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Coleman Building Suite D334, 956 Court Ave., Memphis, TN, 38163, USA

    Lisa K. Jennings

  4. Department of Biological Sciences, College of Arts and Sciences, The University of Memphis, 3774 Walker Ave., Memphis, TN, 38152, USA

    Judith A. Cole

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  1. Jonathan D. McCanless
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Correspondence to Jonathan D. McCanless.

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McCanless, J.D., Jennings, L.K., Bumgardner, J.D. et al. Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the inflammatory-mediated response associated with fracture repair in vitro and ex vivo injection delivery. J Mater Sci: Mater Med 23, 1971–1981 (2012). https://doi.org/10.1007/s10856-012-4672-9

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  • DOI: https://doi.org/10.1007/s10856-012-4672-9

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