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Recent Advances in Controlled Release Technologies for the Co-delivery of Antimicrobial and Osteoconductive Therapeutics

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Racing for the Surface

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Abstract

Bone defects are a significant cause of morbidity in the fields of orthopedics, maxillofacial surgery, and oral implantology, yet their treatment currently faces many challenges including the defect size and location, underlying disease, and microbial infection. Bacteria may be introduced to healing bone through several routes including colonization during open-wound trauma, introduction during surgery, from blood-borne bacteria, or infection of a medical device such as a bone screw. Unfortunately, current treatment strategies are often inadequate and lead to severe and costly consequences. To tackle the problem of infection during bone healing, novel biomaterials such as scaffolds, cements, surface-modified implants, and particles have been developed that comprise both antimicrobial and osteoconductive properties. The antimicrobial properties of these biomaterials typically stem from the addition of antimicrobial agents like antibiotics and silver nanoparticles to the composite material, while osteoconductive properties are conveyed by biomolecules such as growth factors or hydroxyapatite. By controlling modes of delivery and/or release kinetics, these antibacterial and osteoconductive therapeutic constructs are potentially capable of significantly improving bone healing. Recent findings have shown very promising results in the application of these constructs with dual functions in treating infected bone defects. Here, we summarize the advances within the last decade in particle technologies, implant coatings, tissue engineering, and bone cements with both antimicrobial and osteoconductive activity with an emphasis on fabrication and the performance of constructs in various in vitro and in vivo models.

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Abbreviations

Ag-HA:

Silver-containing hydroxyapatite

AgNP:

Silver nanoparticle

AgNP/GS:

Silver nanoparticle gentamicin

AgNP-BHAC:

Silver nanoparticle-doped hydroxyapatite coatings with oriented block arrays

AgNPPGA:

Poly(l-glutamic acid)-capped silver nanoparticles

ALP:

Alkaline phosphatase

Bbr:

Berberine

BMP:

Bone morphogenetic protein

BMSC:

Bone marrow-derived mesenchymal stem/stromal cells

CAP:

Calcium phosphate

CD:

Zero-dimensional carbon dot

CFU:

Colony forming unit

CL:

Clindamycin phosphate

CMCS:

O-carboxymethyl chitosan

Col I:

Type I collagen/procollagen

CS:

Chitosan

CT:

Computed tomography

Cu:

Copper

E. coli :

Escherichia coli

F:

Fluorine

Fe:

Iron

GR-HA:

Glass-reinforced hydroxyapatite

GS:

Gentamicin sulfate

HA:

Hydroxyapatite

IGF-1:

Insulin-like growth factor 1

LbL:

Layer-by-layer (deposition)

MCPM:

Monocalcium phosphate monohydrate

MIC:

Minimum inhibitory concentration

MRSA:

Methicillin-resistant Staphylococcus aureus

MSC:

Mesenchymal stem cell

nHA:

Nanohydroxyapatite

NPs:

Nanoparticles

NT:

Nanotube

OCN:

Osteocalcin

P. aeruginosa :

Pseudomonas aeruginosa

PBS:

Phosphate buffered saline

PCL:

Polycaprolactone

PDLLA:

Poly(d,l-lactide)

PLGA:

Poly(lactic co-glycolic acid)

PM:

PLGA Microparticles

QRT-PCR:

Quantitative real-time polymerase chain reaction

RUNX2:

Runt-related transcription factor 2

S. albus :

Staphylococcus albus

S. aureus :

Staphylococcus aureus

S. epidermidis :

Staphylococcus epidermidis

SBA-15:

Mesoporous silica nanoparticle

SEM:

Scanning electron microscopy

SNPSA:

Silver nanoparticle/poly(dl-lactic-co-glycolic acid)(PLGA)-coated stainless steel alloy

Sr:

Strontium

SR:

Strontium ranelate

TCP:

Tricalcium phosphate

Ti:

Titanium

TNT:

Titania nanotubes

XRD:

X-ray diffraction

Zn:

Zinc

ZnO:

Zinc oxide

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Authors and Affiliations

  1. Department of Biomedical Engineering, Binghamton University (SUNY), Binghamton, NY, USA

    Chukwuazam Nwasike, Kyle Reeser, Erin Purr & Chendong Han

  2. Interdisciplinary Faculty of Toxicology and Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA

    Yizhong Liu

  3. Department of Electrical and Biomedical Engineering, University of Vermont, Burlington, VT, USA

    Jaspreet Singh Nagi & Amber L. Doiron

Authors
  1. Chukwuazam Nwasike
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  2. Kyle Reeser
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  3. Yizhong Liu
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  4. Jaspreet Singh Nagi
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  5. Erin Purr
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  6. Chendong Han
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  7. Amber L. Doiron
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Corresponding author

Correspondence to Amber L. Doiron .

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Editors and Affiliations

  1. Department of Orthopaedics School of Medicine, West Virginia University, Morgantown, WV, USA

    Bingyun Li

  2. AO Research Institute Davos, Davos Platz, Graubünden, Switzerland

    Thomas Fintan Moriarty

  3. Department of Chemical Engineering, Northeastern University, Boston, MA, USA

    Thomas Webster

  4. Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB, Canada

    Malcolm Xing

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Nwasike, C. et al. (2020). Recent Advances in Controlled Release Technologies for the Co-delivery of Antimicrobial and Osteoconductive Therapeutics. In: Li, B., Moriarty, T., Webster, T., Xing, M. (eds) Racing for the Surface. Springer, Cham. https://doi.org/10.1007/978-3-030-34471-9_2

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