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Self-complementary AAV2.5-BMP2-coated femoral allografts mediated superior bone healing versus live autografts in mice with equivalent biomechanics to unfractured femur. | LitMetric

AI Article Synopsis

  • Structural allografts for bone defects have limited natural ability to integrate and heal, highlighting the need for improved methods.
  • Researchers compared two approaches: a minimally effective viral coating (ssAAV-BMP2) and a more successful self-complementary virus variant (scAAV2.5-BMP2).
  • The scAAV2.5-BMP2 significantly enhanced bone healing, leading to new bone formation and superior mechanical strength, proving it a better option for treating critical bone defects.

Article Abstract

Structural allografts used for critical bone defects have limited osteogenic properties for biointegration. Although ex vivo tissue-engineered constructs expressing bone morphogenetic protein-2 (BMP2) have demonstrated efficacy in critical defect models, similar success has not been achieved with off-the-shelf acellular approaches, including allografts coated with freeze-dried single-stranded adeno-associated virus (ssAAV-BMP2). To see whether the self-complementary AAV serotype 2.5 vector (scAAV2.5-BMP2) could overcome this, we performed side-by-side comparisons in vitro and in the murine femoral allograft model. Although ssAAV-BMP2 was unable to induce BMP2 expression and differentiation of C3H10T1/2 cells in culture, scAAV2.5-BMP2 transduction led to dose-dependent BMP2 expression and alkaline phosphatase activity, and displayed a 25-fold increased transduction efficiency in vivo. After 6 weeks, the ssAAV-BMP2 coating failed to demonstrate any significant effects. However, all allografts coated with 10(10) scAAV2.5-BMP2 formed a new cortical shell that was indistinguishable to that formed by live autografts. Additionally, coated allografts experienced reduced resorption resulting in a threefold increase in graft bone volume versus autograft. This led to biomechanical superiority versus both allografts and autografts, and equivalent torsional rigidity to unfractured femur. Collectively, these results demonstrate that scAAV2.5-BMP2 coating overcomes the major limitations of structural allografts, which can be used to heal critical defects of any size.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149158PMC
http://dx.doi.org/10.1038/mt.2010.294DOI Listing

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