Oxidation-Responsive, Settable Bone Substitute Composites for Regenerating Critically-Sized Bone Defects

Details

• Personal Author:
  Addison AE ; Ahmed A ; Bruce KA ; Dos Santos RL ; Hunn BE ; Marques DW ; Martin JR
• Description:
  Critically-sized bone defects that cannot spontaneously heal on their own remain a significant problem in the clinic. Synthetic polymeric implants are promising therapies for improving bone healing as they are highly tunable and avoid the potential complications associated with autologous bone grafts. However, biostable implants such as poly(methyl methacrylate) (PMMA) suffer from numerous shortcomings including negligible biodegradability and limited osseointegration with bone. Hydrolytically-degradable polymeric implants such as poly(caprolactone) (PCL) or poly(lactic-co-glycolic acid) (PLGA) have shown promise facilitating bone growth before being resorbed, but matching the degradation rate of these polyesters with the rate of bone regeneration continues to be an engineering challenge. To address these limitations with current synthetic bone implant materials, cell-degradable polymer/hydroxyapatite composites were developed as in situ-curing bone substitutes. The polymeric component was formulated from a thioketal (TK) dithiol linker and a tri-functional epoxy to facilitate rapid crosslinking upon deployment. To enable biologically-responsive implant resorption, the TK unit is specifically cleaved by cell-produced reactive oxygen species (ROS). TK bone substitutes possessed tunable curing and mechanical properties, were selectively degraded in dose-dependent concentrations of ROS, were non-cytotoxic, and demonstrated significantly greater bone regeneration capacity than PMMA in a critically-sized rat skull defect model. These combined results highlight the therapeutic potential of cell-degradable bone void fillers compared against conventional polymeric bone implants. [Description provided by NIOSH]
• Subjects:
  Occupational Health Safety
• Keywords:
  Biological Materials Biomedical Engineering Bone Disorders Reactive Oxygen Species ROS Skeletal Disorders
• ISSN:
  2047-4830
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Chicago Region [OSHA] ; Ohio
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  13
• Issue:
  8
• NIOSHTIC Number:
  nn:20070594
• Citation:
  Biomater Sci 2025 Apr; 13(8):1975-1992
• Email:
  marti7j3@ucmail.uc.edu
• Federal Fiscal Year:
  2025
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Biomaterials Science
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cae01e8a1b47cbe986cd652544980cd66128dbaa515972adc9381a855a4631083495a9ececa829cddd5729741bfdc5165f2463b4e6c4c3ac3b21305b291c15c6
• Download URL:
  https://stacks.cdc.gov/view/cdc/208773/cdc_208773_DS1.pdf
• File Type:
  [PDF - 2.42 MB ]