Journal of Materials Science: Materials in Medicine

, Volume 23, Issue 8, pp 1971-1981

First online:

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. McCanlessAffiliated withBiomedical Engineering Department, Herff College of Engineering, The University of Memphis Email author 
  • , Lisa K. JenningsAffiliated withDepartment of Internal Medicine, College of Medicine, The University of Tennessee Health Science CenterVascular Biology Center of Excellence, The University of Tennessee Health Science Center
  • , Joel D. BumgardnerAffiliated withBiomedical Engineering Department, Herff College of Engineering, The University of Memphis
  • , Judith A. ColeAffiliated withDepartment of Biological Sciences, College of Arts and Sciences, The University of Memphis
  • , Warren O. HaggardAffiliated withBiomedical Engineering Department, Herff College of Engineering, The University of Memphis

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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.