title: Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the inflammatory-mediated response associated with fracture repair in vitro and ex vivo injection delivery.
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.
authors.affiliation: Biomedical Engineering Department, Herff College of Engineering, The University of Memphis, Memphis, TN 38152, USA. jonathan_mccanless@excite.com
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: McCanless
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Jennings
authors.forename: Joel D
authors.initials: JD
authors.lastname: Bumgardner
authors.forename: Judith A
authors.initials: JA
authors.lastname: Cole
authors.forename: Warren O
authors.initials: WO
authors.lastname: Haggard
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D018786:Bone Substitutes / Q000008:administration & dosage / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D050723:Fractures, Bone / Q000276:immunology* / Q000628:therapy; D020723:Glucuronic Acid / Q000737:chemistry; D006406:Hematoma / Q000276:immunology* / Q000628:therapy; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007267:Injections; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D017713:Platelet Transfusion / Q000379:methods*; D051381:Rats
chemical_list: D000464:Alginates; D018786:Bone Substitutes; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D020723:Glucuronic Acid; C020243:calcium phosphate