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

被引:10
作者
Grey, Zachary J. [1 ]
Howie, R. Nicole [1 ]
Durham, Emily L. [1 ]
Hall, Sarah Rose [1 ]
Helke, Kristi L. [2 ]
Steed, Martin B. [3 ]
LaRue, Amanda C. [4 ,5 ]
Muise-Helmericks, Robin C. [6 ]
Cray, James J. [7 ]
机构
[1] Med Univ South Carolina, Dept Oral Hlth Sci, Charleston, SC 29425 USA
[2] Med Univ South Carolina, Dept Comparat Med, Div Lab Anim Resources, 30 Courtenay Dr, Charleston, SC 29425 USA
[3] Med Univ South Carolina, Dept Oral & Maxillofacial Surg, Charleston, SC 29425 USA
[4] Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA
[5] Ralph H Johnston Vet Affairs Med Ctr, Dept Vet Affairs, Charleston, SC USA
[6] Med Univ South Carolina, Dept Regenerat Med, Charleston, SC 29425 USA
[7] Ohio State Univ, Coll Med, Div Anat, 1,645 Neil Ave,279 Hamilton Hall, Columbus, OH 43210 USA
关键词
CRITICAL-SIZE; DONOR SITES; MACROPHAGES; FRACTURE; DEFECTS;
D O I
10.1111/wrr.12710
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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 5 mm 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 7-day postoperative time points were used to assess the role that rhBMP-2 plays in modulating inflammation vs. 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 7-day time point. Additionally, while rhBMP-2 administration increased macrophage response, this peptide had a 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.
引用
收藏
页码:335 / 344
页数:10
相关论文
共 42 条
[1]
Amini Ami R., 2012, Critical Reviews in Biomedical Engineering, V40, P363
[2]
Bauer TW, 2000, CLIN ORTHOP RELAT R, P10
[3]
Effects of protein dose and delivery system on BMP-mediated bone regeneration [J].
Boerckel, Joel D. ;
Kolambkar, Yash M. ;
Dupont, Kenneth M. ;
Uhrig, Brent A. ;
Phelps, Edward A. ;
Stevens, Hazel Y. ;
Garcia, Andres J. ;
Guldberg, Robert E. .
BIOMATERIALS, 2011, 32 (22) :5241-5251
[4]
Physican-directed (off-label) use of recombinant bone morphogenic protein-2: let us do it well! [J].
Branch, Charles L., Jr. .
SPINE JOURNAL, 2011, 11 (06) :469-470
[5]
BONE BIOLOGY .1. STRUCTURE, BLOOD-SUPPLY, CELLS, MATRIX, AND MINERALIZATION [J].
BUCKWALTER, JA ;
GLIMCHER, MJ ;
COOPER, RR ;
RECKER, R .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1995, 77A (08) :1256-1275
[6]
Testing the Critical Size in Calvarial Bone Defects: Revisiting the Concept of a Critical-Size Defect [J].
Cooper, Gregory M. ;
Mooney, Mark P. ;
Gosain, Arun K. ;
Campbell, Phil G. ;
Losee, Joseph E. ;
Huard, Johnny .
PLASTIC AND RECONSTRUCTIVE SURGERY, 2010, 125 (06) :1685-1692
[7]
Costantino Peter D, 2002, Facial Plast Surg, V18, P13
[8]
BMP-2-Regenerated Calvarial Bone A Biomechanical Appraisal in a Large Animal Model [J].
Cray, James, Jr. ;
Henderson, Sarah E. ;
Smith, Darren M. ;
Kinsella, Christopher R., Jr. ;
Bykowski, Michael ;
Cooper, Gregory M. ;
Almarza, Alejandro J. ;
Losee, Joseph E. .
ANNALS OF PLASTIC SURGERY, 2014, 73 (05) :591-597
[9]
Optimizing bone wound healing using BMP2 with absorbable collagen sponge and Talymed nanofiber scaffold [J].
Durham, Emily L. ;
Howie, R. Nicole ;
Hall, SarahRose ;
Larson, Nicholas ;
Oakes, Brayden ;
Houck, Reed ;
Grey, Zachary ;
Steed, Martin ;
LaRue, Amanda C. ;
Muise-Helmericks, Robin ;
Cray, James .
JOURNAL OF TRANSLATIONAL MEDICINE, 2018, 16
[10]
Involvement of calvarial stem cells in healing: A regional analysis of large cranial defects [J].
Durham, Emily L. ;
Howie, R. Nicole ;
Houck, Reed ;
Oakes, Brayden ;
Grey, Zachary ;
Hall, SarahRose ;
Steed, Martin ;
LaRue, Amanda ;
Muise-Helmericks, Robin ;
Cray, James .
WOUND REPAIR AND REGENERATION, 2018, 26 (05) :359-365