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

  • Jonathan D. McCanless
  • Lisa K. Jennings
  • Joel D. Bumgardner
  • Judith A. Cole
  • Warren O. Haggard
Article

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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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Jonathan D. McCanless
    • 1
  • Lisa K. Jennings
    • 2
    • 3
  • Joel D. Bumgardner
    • 1
  • Judith A. Cole
    • 4
  • Warren O. Haggard
    • 1
  1. 1.Biomedical Engineering DepartmentHerff College of Engineering, The University of MemphisMemphisUSA
  2. 2.Department of Internal MedicineCollege of Medicine, The University of Tennessee Health Science CenterMemphisUSA
  3. 3.Vascular Biology Center of ExcellenceThe University of Tennessee Health Science CenterMemphisUSA
  4. 4.Department of Biological SciencesCollege of Arts and Sciences, The University of MemphisMemphisUSA

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