Sub‐clinical dose of bone morphogenetic protein‐2 does not precipitate rampant, sustained inflammatory response in bone wound healing

Autor:	Robin C. Muise-Helmericks, Sarah Rose Hall, James J. Cray, Kristi L. Helke, Amanda C. LaRue, R. Nicole Howie, Zachary Grey, Emily Durham, Martin B. Steed
Rok vydání:	2019
Předmět:	Combination therapy Bone pathology medicine.medical_treatment Macrophage polarization Bone Morphogenetic Protein 2 Inflammation Dermatology Pharmacology Bone morphogenetic protein 2 Article Fractures Bone Mice 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Osteogenesis Absorbable Implants medicine Animals Macrophage Wound Healing Tissue Scaffolds business.industry Mice Inbred C57BL Disease Models Animal Cytokine Surgery Collagen medicine.symptom Wound healing business
Zdroj:	Wound Repair Regen
ISSN:	1524-475X 1067-1927
DOI:	10.1111/wrr.12710
Popis:	Large bone injuries, defects, and chronic wounds present a major problem for medicine. Several therapeutic strategies are used clinically to precipitate bone including a combination therapy delivering osteoinductive bone morphogenetic protein 2 (rhBMP-2) via an osteoconductive scaffold (absorbable collagen sponge, ACS) (i.e. INFUSE). Adverse side effects reportedly associated with rhBMP2 administration include rampant inflammation and clinical failures. Although acute inflammation is necessary for proper healing in bone, inflammatory cascade dysregulation can result in sustained tissue damage and poor healing. We hypothesized that a subclinical dose of rhBMP2 modeled in the murine calvarial defect would not precipitate alterations to inflammatory markers during acute phases of bone wound healing. We utilized the 5mm critical size calvarial defect in C57BL6 wild-type mice which were subsequently treated with ACS and a subclinical dose of rhBMP2 shown to be optimal for healing. Three and seven-day post-operative time points were used to assess the role that rhBMP-2 plays in modulating inflammation versus ACS alone by cytokine array and histological interrogation. Data revealed that rhBMP-2 delivery resulted in substantial modulation of several markers associated with inflammation, most of which decreased to levels similar to control by the seven day time point. Additionally, while rhBMP-2 administration increased macrophage response, this peptide had little noticeable effect on traditional markers of macrophage polarization (M1-iNOS, M2-Arg1). These results suggest that rhBMP-2 delivered at a lower dose does not precipitate rampant inflammation. Thus, an assessment of dosing for rhBMP-2 therapies may lead to better healing outcomes and less surgical failure.
Databáze:	OpenAIRE
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