Adenovirus BMP2-induced osteogenesis in combination with collagen carriers

Zbigniew Gugala, Alan R. Davis, Christine M. Fouletier-Dilling, Francis H. Gannon, Ronald Lindsey, Elizabeth A. Olmsted-Davis

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Adenovirus BMP2 gene therapy has potential of a robust endogenous BMP2 production, while circumventing many of the problems currently associated with recombinant BMP2. The study objective was to determine and compare the ability of adenovirus BMP2 ex vivo gene therapy in combination with three types of collagen carriers to release BMP2 in vitro and to induce heterotopic bone formation in vivo. Human CD45-negative bone marrow cells were ex vivo transduced with a chimeric Ad5F35BMP2. The bioactivity of BMP2 produced by the transduced cells without a carrier, or in combination with three types of collagen carriers (injectable gel, microporous sponge, collagen-mineral composite) was measured and compared to rhBMP2. The heterotopic osteoinductivity assay was performed in immunocompromised NOD/SCID mice. A statistically significant decrease in the amount of rhBMP2 and adenoviral BMP2 released in vitro from the collagen-mineral composite carrier was noted (21% and 12%, respectively), whereas the amounts of rhBMP2 and adenoviral BMP2 released from the gel or sponge carriers were comparable. In vivo, 14 days post-implantation, no bone was formed consistently in groups with the empty Ad5F35HM4 control vector. New bone formation was evident radiographically and histologically in all groups with the Ad5F35BMP2-transduced cells irrespective of the presence or absence of a carrier. The presence of a carrier resulted in osteogenesis limited to the implantation site, and was most pronounced for solid (sponge, composite) carriers. The physical characteristics of the carrier determined the new bone spatial distribution at the site. Solid carriers reduced the clearance of AD5F35-transduced cells by the host immune cells. Adenoviral ex vivo BMP2 gene therapy in combination with collagen carriers with distinct physical characteristics offers the prospects of adjusting this approach to optimally match the specific therapeutic requirements.

Original languageEnglish (US)
Pages (from-to)4469-4479
Number of pages11
JournalBiomaterials
Volume28
Issue number30
DOIs
StatePublished - Oct 2007
Externally publishedYes

Fingerprint

Collagen
Adenoviridae
Osteogenesis
Bone
Gene therapy
Porifera
Genetic Therapy
Minerals
Composite materials
Gels
Bone and Bones
Inbred NOD Mouse
SCID Mice
Bioactivity
Bone Marrow Cells
Spatial distribution
Assays
Cells
Injections
In Vitro Techniques

Keywords

  • Adenovirus
  • Bone morphogenetic protein
  • Collagen carriers
  • Gene therapy
  • Osteogenesis

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Gugala, Z., Davis, A. R., Fouletier-Dilling, C. M., Gannon, F. H., Lindsey, R., & Olmsted-Davis, E. A. (2007). Adenovirus BMP2-induced osteogenesis in combination with collagen carriers. Biomaterials, 28(30), 4469-4479. https://doi.org/10.1016/j.biomaterials.2007.07.007

Adenovirus BMP2-induced osteogenesis in combination with collagen carriers. / Gugala, Zbigniew; Davis, Alan R.; Fouletier-Dilling, Christine M.; Gannon, Francis H.; Lindsey, Ronald; Olmsted-Davis, Elizabeth A.

In: Biomaterials, Vol. 28, No. 30, 10.2007, p. 4469-4479.

Research output: Contribution to journalArticle

Gugala, Z, Davis, AR, Fouletier-Dilling, CM, Gannon, FH, Lindsey, R & Olmsted-Davis, EA 2007, 'Adenovirus BMP2-induced osteogenesis in combination with collagen carriers', Biomaterials, vol. 28, no. 30, pp. 4469-4479. https://doi.org/10.1016/j.biomaterials.2007.07.007
Gugala, Zbigniew ; Davis, Alan R. ; Fouletier-Dilling, Christine M. ; Gannon, Francis H. ; Lindsey, Ronald ; Olmsted-Davis, Elizabeth A. / Adenovirus BMP2-induced osteogenesis in combination with collagen carriers. In: Biomaterials. 2007 ; Vol. 28, No. 30. pp. 4469-4479.
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