Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

被引:20
作者
Beenken, Karen E. [1 ]
Campbell, Mara J. [1 ]
Ramirez, Aura M. [1 ]
Alghazali, Karrar [2 ]
Walker, Christopher M. [1 ]
Jackson, Bailey [2 ]
Griffin, Christopher [2 ]
King, William [2 ]
Bourdo, Shawn E. [2 ]
Rifkin, Rebecca [3 ]
Hecht, Silke [4 ]
Meeker, Daniel G. [1 ]
Anderson, David E. [3 ]
Biris, Alexandru S. [2 ]
Smeltzer, Mark S. [1 ]
机构
[1] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA
[2] Univ Arkansas, Ctr Integrat Nanotechnol Sci, Little Rock, AR 72204 USA
[3] Univ Tennessee, Coll Vet Med, Dept Large Anim Clin Sci, Knoxville, TN USA
[4] Univ Tennessee, Coll Vet Med, Dept Small Anim Clin Sci, Knoxville, TN USA
关键词
IMPACT; OSTEOMYELITIS; PATHOGENESIS; SARA; AGR;
D O I
10.1038/s41598-021-89830-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (mu CT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.
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页数:10
相关论文
共 31 条
[1]
Bone-tissue engineering: complex tunable structural and biological responses to injury, drug delivery, and cell-based therapies [J].
Alghazali, Karrer M. ;
Nima, Zeid A. ;
Hamzah, Rabab N. ;
Dhar, Madhu S. ;
Anderson, David E. ;
Biris, Alexandru S. .
DRUG METABOLISM REVIEWS, 2015, 47 (04) :431-454
[2]
Impact of the functional status of saeRS on in vivo phenotypes of Staphylococcus aureussarA mutants [J].
Beenken, Karen E. ;
Mrak, Lara N. ;
Zielinska, Agnieszka K. ;
Atwood, Danielle N. ;
Loughran, Allister J. ;
Griffin, Linda M. ;
Matthews, K. Alice ;
Anthony, Allison M. ;
Spencer, Horace J. ;
Skinner, Robert A. ;
Post, Ginell R. ;
Lee, Chia Y. ;
Smeltzer, Mark S. .
MOLECULAR MICROBIOLOGY, 2014, 92 (06) :1299-1312
[3]
Impact of Extracellular Nuclease Production on the Biofilm Phenotype of Staphylococcus aureus under In Vitro and In Vivo Conditions [J].
Beenken, Karen E. ;
Spencer, Horace ;
Griffin, Linda M. ;
Smeltzer, Mark S. .
INFECTION AND IMMUNITY, 2012, 80 (05) :1634-1638
[4]
Pathologic Fractures in Children with Acute Staphylococcus aureus Osteomyelitis [J].
Belthur, Mohan V. ;
Birchansky, Sherri B. ;
Verdugo, Alejandro A. ;
Mason, Edward O., Jr. ;
Hulten, Kristina G. ;
Kaplan, Sheldon L. ;
Smith, E. O'Brian ;
Phillips, William A. ;
Weinberg, Jacob .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2012, 94A (01) :34-42
[5]
Blanchette Krystle A, 2018, J Bone Jt Infect, V3, P50, DOI 10.7150/jbji.23423
[6]
Commercially available bone graft substitutes: the impact of origin and processing on graft functionality [J].
Bow, Austin ;
Anderson, David E. ;
Dhar, Madhu .
DRUG METABOLISM REVIEWS, 2019, 51 (04) :533-544
[7]
Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390 [J].
Cassat, James ;
Dunman, Paul M. ;
Murphy, Ellen ;
Projan, Steven J. ;
Beenken, Karen E. ;
Palm, Katherine J. ;
Yang, Soo-Jin ;
Rice, Kelly C. ;
Bayles, Kenneth W. ;
Smeltzer, Mark S. .
MICROBIOLOGY-SGM, 2006, 152 :3075-3090
[8]
A Secreted Bacterial Protease Tailors the Staphylococcus aureus Virulence Repertoire to Modulate Bone Remodeling during Osteomyelitis [J].
Cassat, James E. ;
Hammer, Neal D. ;
Campbell, J. Preston ;
Benson, Meredith A. ;
Perrien, Daniel S. ;
Mrak, Lara N. ;
Smeltzer, Mark S. ;
Torres, Victor J. ;
Skaar, Eric P. .
CELL HOST & MICROBE, 2013, 13 (06) :759-772
[9]
Surgical Treatment of Osteomyelitis [J].
Cierny, George, III .
PLASTIC AND RECONSTRUCTIVE SURGERY, 2011, 127 (01) :190S-204S
[10]
Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis [J].
Ford, Caleb A. ;
Cassat, James E. .
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, 2017, 15 (09) :851-860