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Related Concept Videos

Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
Bone Remodeling and Repair01:31

Bone Remodeling and Repair

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...

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Related Experiment Video

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Visualizing Angiogenesis by Multiphoton Microscopy In Vivo in Genetically Modified 3D-PLGA/nHAp Scaffold for Calvarial Critical Bone Defect Repair
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Recent advances in gene delivery for structural bone allografts.

Hani A Awad1, Xinping Zhang, David G Reynolds

  • 1Department of Biomedical Engineering, The Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14620, USA. Hani_Awad@urmc.rochester.edu

Tissue Engineering
|May 24, 2007
PubMed
Summary

Gene therapy using recombinant adeno-associated virus (rAAV) revitalizes bone allografts. Delivering specific genes like caAlk2, VEGF, and RANKL promotes bone formation, vascularization, and remodeling for improved bone defect repair.

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Gene Therapy

Background:

  • Massive bone defects pose significant challenges in repair.
  • Current strategies include mesenchymal stem cells (MSCs), bone morphogenetic proteins (BMPs), and gene therapy.
  • Effective bone grafting requires osteoinduction, angiogenesis, and remodeling.

Purpose of the Study:

  • To evaluate the efficacy of recombinant adeno-associated virus (rAAV)-mediated gene transfer for revitalizing bone allografts.
  • To investigate the osteogenic, angiogenic, and remodeling effects of specific gene deliveries in a murine femoral model.

Main Methods:

  • Development of a murine femoral allograft model.
  • Coating allografts with rAAV expressing constitutively active BMP type I receptor Alk2 (caAlk2) or vascular endothelial growth factor (VEGF) with receptor activator of NF-kappa B ligand (RANKL).
  • Histomorphometric analysis and micro computed tomography (muCT) imaging to assess bone healing and vascularization.

Main Results:

  • rAAV-mediated delivery of caAlk2 induced significant osteoinduction, forming a mineralized callus resembling autograft healing.
  • Co-delivery of VEGF and RANKL via rAAV significantly enhanced vascularization and remodeling of structural allografts.
  • Control allografts treated with rAAV-LacZ showed no significant improvements, resembling necrotic allografts.

Conclusions:

  • Gene delivery innovations, particularly with rAAV, offer a promising therapeutic strategy for tissue engineering of structural bone.
  • rAAV-mediated gene transfer can effectively revitalize bone allografts, promoting osteogenesis, angiogenesis, and remodeling.
  • These findings suggest potential clinical applications for challenging bone defect indications.