J Korean Soc Spine Surg.  2003 Dec;10(4):283-289.

Spinal Fusion by Percutaneous OP-1 Gene Delivery

Affiliations
  • 1Department of Orthopaedic Surgery, Kuri Hospital, College of Medicine, Hanyang University. hyparkys@hanyang.ac.kr
  • 2Department of Biomedical Engineering, Johns Hopkins University.
  • 3Department of Orthopaedic Surgery, Johns Hopkins University.

Abstract

STUDY DESIGN: An in-vivo experiment.
OBJECTIVES
To evaluate the feasibility of achieving bone formation by percutaneous gene delivery, with plasmid DNA encoding BMP-7(OP-1). SUMMARY OF LITERATURE REVIEW: Currently, the preferred method for posterolateral spinal fusion involves decortication of the transverse process, followed by a graft of autogenous bone harvested from the iliac crest. Unfortunately, this procedure suffers from significant morbidity, including blood loss, infection and persistent pain at the harvest site. MATERIAL AND METHODS: 24 Sprague-Dawley rats, weighing approximately 250~300 g, were used. The percutaneous injection was attempted above both the L5 transverse processes. The animals were divided into three groups, according to the injection materials: 1) OP-1 gene/collagen, 2) recombinant OP-1 protein/collagen and 3) control of PBS/collagen. At 2 and 4 weeks post-injection, the animals were sacrificed. The gross, radiological and histological findings were analyzed.
RESULTS
No bone was detected grossly by manual palpation or radiography in the groups receiving OP-1 gene/collagen at either time point. The histological findings revealed the initiation of endochondral bone formation within the paraspinal muscle, directly above the L5 transverse process. In the rhOP-1 protein/collagen groups, the gross, radiological and histological findings revealed extensive cartilage and bone formation at both 2 and 4 weeks.
CONCLUSION
In conclusion, the authors confirmed the feasibility of achieving bone formation by percutaneous gene delivery, with plasmid DNA encoding BMP-7(OP-1).

Keyword

Spinal fusion; Percutaneous delivery; OP-1 gene

MeSH Terms

Animals
Cartilage
DNA
Osteogenesis
Palpation
Paraspinal Muscles
Plasmids
Radiography
Rats, Sprague-Dawley
Spinal Fusion*
Transplants
DNA

Figure

  • Fig. 1. In gross and radiographic findings of Op-1 gene and collagen injection group, it doesn’ t show the evidence of bone formation (2 week group after harvest is (A, B) and 4 week group is (C, D).

  • Fig. 2. Histologic findings of Op-1 gene and collagen injection group. (A) It shows loose cartilaginous matrix and non-woven bone matrix in the dorsal injected surface of transverse process in 2 week histologic findings (H-E staining, × 100). (B) It shows the decrease of granulation tissue and atrophy of the muscle cell around the injection site in 4 week histologic findings (H-E staining, × 200).

  • Fig. 3. In gross and radiographic findings of Op-1 protein and collagen injection group, it shows the evidence of bone formation and firm bony union. 4 week group showed more bone formation than 2 week group. In 4 week group, it shows posterior and facet fusion due to abundant bone formation (2 week group after harvest is A, B and 4 week group is C, D).

  • Fig. 4. Histologic findings of Op-1 protein and collagen injection group. (A, B) It shows the newly formed bone around the posterior aspect of transverse process in 2 week whole spine sample and the definite evidence of endochondral ossification (H-E staining, A: × 10, B: × 100). (C, D) In the intertransverse muscle of 4 week histology, it shows maturation of chondrocyte, mature bone, osteoid and bone marrow (H-E staining, C: × 200, D: × 100).

  • Fig. 5. Control group of PBS and collagen injection. It doesn’ t show the cartilage and bone formation in gross, radiographic and histologic findings (H-E staining,× 40).


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