Drug-Free ROS Sponge Polymeric Microspheres Reduce Tissue Damage from Ischemic and Mechanical Injury

Kristin P. O'Grady, Taylor E. Kavanaugh, Hongsik Cho, Hanrong Ye, Mukesh K. Gupta, Megan C. Madonna, Jinjoo Lee, Christine M. O'Brien, Melissa C. Skala, Karen Hasty, Craig L. Duvall

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The inherent antioxidant function of poly(propylene sulfide) (PPS) microspheres (MS) was dissected for different reactive oxygen species (ROS), and therapeutic benefits of PPS-MS were explored in models of diabetic peripheral arterial disease (PAD) and mechanically induced post-traumatic osteoarthritis (PTOA). PPS-MS (∼1 μm diameter) significantly scavenged hydrogen peroxide (H2O2), hypochlorite, and peroxynitrite but not superoxide in vitro in cell-free and cell-based assays. Elevated ROS levels (specifically H2O2) were confirmed in both a mouse model of diabetic PAD and in a mouse model of PTOA, with greater than 5- and 2-fold increases in H2O2, respectively. PPS-MS treatment functionally improved recovery from hind limb ischemia based on ∼15-25% increases in hemoglobin saturation and perfusion in the footpads as well as earlier remodeling of vessels in the proximal limb. In the PTOA model, PPS-MS reduced matrix metalloproteinase (MMP) activity by 30% and mitigated the resultant articular cartilage damage. These results suggest that local delivery of PPS-MS at sites of injury-induced inflammation improves the vascular response to ischemic injury in the setting of chronic hyperglycemia and reduces articular cartilage destruction following joint trauma. These results motivate further exploration of PPS as a stand-alone, locally sustained antioxidant therapy and as a material for microsphere-based, sustained local drug delivery to inflamed tissues at risk of ROS damage.

Original languageEnglish (US)
Pages (from-to)1251-1264
Number of pages14
JournalACS Biomaterials Science and Engineering
Volume4
Issue number4
DOIs
StatePublished - Apr 9 2018

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Microspheres
Reactive Oxygen Species
Propylene
Tissue
Oxygen
Pharmaceutical Preparations
Cartilage
Antioxidants
Hypochlorous Acid
Peroxynitrous Acid
Hemoglobin
Sulfides
Matrix Metalloproteinases
Drug delivery
Hydrogen peroxide
Superoxides
Hydrogen Peroxide
propylene sulfide
Polypropylenes
Assays

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering

Cite this

Drug-Free ROS Sponge Polymeric Microspheres Reduce Tissue Damage from Ischemic and Mechanical Injury. / O'Grady, Kristin P.; Kavanaugh, Taylor E.; Cho, Hongsik; Ye, Hanrong; Gupta, Mukesh K.; Madonna, Megan C.; Lee, Jinjoo; O'Brien, Christine M.; Skala, Melissa C.; Hasty, Karen; Duvall, Craig L.

In: ACS Biomaterials Science and Engineering, Vol. 4, No. 4, 09.04.2018, p. 1251-1264.

Research output: Contribution to journalArticle

O'Grady, KP, Kavanaugh, TE, Cho, H, Ye, H, Gupta, MK, Madonna, MC, Lee, J, O'Brien, CM, Skala, MC, Hasty, K & Duvall, CL 2018, 'Drug-Free ROS Sponge Polymeric Microspheres Reduce Tissue Damage from Ischemic and Mechanical Injury', ACS Biomaterials Science and Engineering, vol. 4, no. 4, pp. 1251-1264. https://doi.org/10.1021/acsbiomaterials.6b00804
O'Grady, Kristin P. ; Kavanaugh, Taylor E. ; Cho, Hongsik ; Ye, Hanrong ; Gupta, Mukesh K. ; Madonna, Megan C. ; Lee, Jinjoo ; O'Brien, Christine M. ; Skala, Melissa C. ; Hasty, Karen ; Duvall, Craig L. / Drug-Free ROS Sponge Polymeric Microspheres Reduce Tissue Damage from Ischemic and Mechanical Injury. In: ACS Biomaterials Science and Engineering. 2018 ; Vol. 4, No. 4. pp. 1251-1264.
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