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Surgical Bone Implantation Technique for Rat Tibia Models of Diabetes and Osteoporosis
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A Multi-Functional Implant Induces Bone Formation in a Diabetic Model.

Behnoush Khorsand1, Timothy M Acri1, Anh-Vu Do1

  • 1Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, 52242, USA.

Advanced Healthcare Materials
|August 21, 2020
PubMed
Summary

Diabetic patients experience poor bone fracture healing. A novel therapy combining insulin, vitamin D3, and genes for bone morphogenetic protein-2 and fibroblast growth factor-2 significantly enhances bone regeneration in diabetic rats.

Keywords:
Insulinbone morphogenetic protein-2bone regenerationdiabetes mellitusfibrin gelsfibroblast growth factor-2nonviral gene deliverypoly lactic-co-glycolic acidpolyethyleniminevitamin D3

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Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Diabetic Complications

Background:

  • Diabetes mellitus (DM) impairs bone fracture healing.
  • Previous therapies using individual growth factors or hormones showed limited success.
  • A combination therapy is needed for effective bone regeneration in diabetic patients.

Purpose of the Study:

  • To investigate the efficacy of local delivery of insulin (INS), vitamin D3 (VD3), bone morphogenetic protein-2 (BMP-2), and fibroblast growth factor-2 (FGF-2) genes for ectopic bone formation.
  • To develop a composite delivery system for these therapeutic agents in a Type-2 diabetic rat model.

Main Methods:

  • A composite delivery system was created using poly(lactic-co-glycolic acid) microparticles loaded with INS and VD3, embedded in a fibrin gel and collagen matrix.
  • Polyethylenimine (PEI) complexed with plasmid DNA encoding BMP-2 and FGF-2 (PEI-(pBMP-2+pFGF-2) nanoplexes) were incorporated into the matrix.
  • The composite was tested in a submuscular osteoinduction model in Type-2 diabetic rats.

Main Results:

  • Local delivery of INS, VD3, and PEI-(pBMP-2+pFGF-2) significantly enhanced bone generation compared to control groups.
  • The synergistic effect of the combined therapy promoted superior bone formation in the diabetic model.

Conclusions:

  • The developed composite delivery system effectively promotes bone regeneration in diabetic rats.
  • This combination therapy holds promise for treating bone fractures in patients with diabetes mellitus.