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Hybrid constructs for craniofacial reconstruction: sustained gene delivery using demineralized bone matrix putty
James M Smartt1, Ines C Lin, Elizabeth Kim
1Division of Plastic Surgery, The University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia, 19104, USA.
Annals of Plastic Surgery
|May 29, 2004
Summary
This study shows demineralized bone matrix putty effectively delivers genes using adenoviral vectors for sustained, site-directed gene transfer in bone and dural cells. Optimal dosing prevents toxicity while ensuring long-term gene expression.
Area of Science:
- Biomaterials Engineering
- Gene Therapy
- Tissue Engineering
Background:
- Demineralized bone matrix (DBM) putty is a bone graft substitute.
- Adenoviral vectors are common tools for gene delivery.
- Sustained, site-directed gene delivery remains a challenge in regenerative medicine.
Purpose of the Study:
- To evaluate the efficacy of a hybrid construct combining DBM putty and adenoviral vectors for gene transfer.
- To determine optimal dosing and sustainability of gene transfer in osteoblasts and dural cells.
- To assess the potential of this approach for site-directed gene therapy.
Main Methods:
- Hybrid constructs were formed by mixing DBM putty with varying concentrations of AdGFP.
- Constructs were co-cultured with fetal murine calvarial osteoblasts and dural cells at different multiplicities of infection (MOI).
- Gene transfer sustainability was assessed over 30 days by re-introducing constructs to new cells.
Main Results:
- Optimal gene transfer occurred at MOI 10 for osteoblasts and MOI 100 for dural cells.
- Higher viral concentrations led to toxicity in most samples.
- Sustained gene transfer to both cell types was observed throughout the 30-day experimental period.
Conclusions:
- Adenoviral vectors can be effectively incorporated into DBM putty for sustained gene delivery.
- This hybrid construct shows promise for site-directed gene therapy applications.
- The findings support the use of DBM-adenoviral vector composites for enhanced regenerative therapies.