J Korean Neurosurg Soc.  2018 Sep;61(5):559-567. 10.3340/jkns.2017.0297.

Biodegradable Screws Containing Bone Morphogenetic Protein-2 in an Osteoporotic Rat Model

Affiliations
  • 1Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea.
  • 2Laboratory of Stem Cell Therapy, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. neuri71@gmail.com
  • 3Department of Biostatistic Consulting, Soon Chun Hyang Medical Center, Bucheon, Korea.
  • 4Department of Neurological Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 5Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 6Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.

Abstract


OBJECTIVE
The aim of this study was to evaluate the effect for biodegradable screws containing bone morphogenetic protein-2 (BMP-2) in an osteoporotic rat model.
METHODS
Twenty-four female Wistar rat (250-300 g, 12 weeks of age) were randomized into four groups. Three groups underwent bilateral ovariectomy (OVX). Biodegradable screws with or without BMP-2 were inserted in the proximal tibia in two implantation groups. The extracted proximal metaphysis of the tibiae were scanned by exo-vivo micro-computed tomography. Evaluated parameters included bone mineral density (BMD), trabecular bone volume (BV/TV), trabecular number, trabecular thickness, and trabecular separation (Tb.Sp). The tibia samples were pathologically evaluated by staining with by Hematoxylin and Eosin, and trichrome.
RESULTS
Trabecular formation near screw insertion site was evident only in rats receiving BMP-2 screws. BMD and BV/TV significantly differed between controls and the OVX and OVX with screw groups. However, there were no significant differences between control and OVX with screw BMP groups. Tb.Sp significantly differed between control and OVX and OVX with screw groups (p < 0.05), and between the OVX and OVX with screw BMP group (p < 0.05), with no statistically significant difference between control and OVX with screw BMP groups. Over the 12 weeks after surgery, bone lamellae in direct contact with the screw developed more extensive and thicker trabecular bone around the implant in the OVX with screw BMP group compared to the OVX with screw group.
CONCLUSION
Biodegradable screws containing BMP-2 improve nearby bone conditions and enhance ostoeintegration between the implant and the osteoporotic bone.

Keyword

Osteoporosis; Models, Animal; Screw, Animal; Bone morphogenetic protein 2

MeSH Terms

Animals
Bone Density
Bone Morphogenetic Protein 2
Eosine Yellowish-(YS)
Female
Hematoxylin
Humans
Models, Animal*
Osteoporosis
Ovariectomy
Rats*
Tibia
Bone Morphogenetic Protein 2
Eosine Yellowish-(YS)
Hematoxylin

Figure

  • Fig. 1. Details of screw modification. A : Two 0.5 mm perpendicuallry crossed holes were made. B and C : A 1×5 mm absorbable collagen sponge (Collatape®; Zimmer Dental, Carlsbad, CA, USA) was inserted in the hole (arrow) as a carrier for the delivery of bone morphogenetic protein-2.

  • Fig. 2. Details of screw implantation. A : After dissection of soft tissue, a hole was made using a 1.4-mm rotary drill 5 mm distal from the proximal growth plate, and a screw was inserted. B : There is no wound site infection, dehiscence or swelling of the soft tissue (circle).

  • Fig. 3. In vitro BMP-2 release. An initial peak of release was evident in the first 2 hours after contact with fluids, with a steady release of 0.1 to 0.4% per day in the following days. BMP-2 : bone morphogenetic protein-2.

  • Fig. 4. Changes of the body weight of rats. The mean body weight increased over the 12 weeks. Body weight in the OVX, OVX with screw and OVX with screw BMP groups was higher than the control group (p<0.05). *There exists the significant difference between control and OVX with screw. †There exists the significant difference between control and OVX with screw BMP. OVX : ovariectomy, BMP : bone morphogenetic protein.

  • Fig. 5. Representative micro-computed tomography images (upper : sagittal, lower : axial), photographs showing osteoporotic changes of bone in the OVX, OVX with screw and OVX with screw BMP groups. Definite trabecular formation was evident near the screw insertion site only in the OVX with screw BMP group. A : Sham (control) group, B : OVX-induced osteoporosis group, C : OVX and biodegradable screw (OVX with screw) group, D : OVX and BMP-2 containing biodegradable screw (OVX with screw BMP) group. OVX : ovariectomy, BMP : bone morphogenetic protein.

  • Fig. 6. Changes of BMD. BMD of the control group was the highest, with a significant difference between the control and OVX and OVX with screw groups (p<0.05). *p<0.05 compared with control. OVX : ovariectomy, BMP : bone morphogenetic protein.

  • Fig. 7. Summary of micro-computed tomography findings. A : BV/TV of the control group was highest, with a significant difference between the control and OVX and OVX with screw groups (p<0.05). B : Significant difference in Tb.N was evident between control and the other groups (p<0.05). C : Tb.Th of the OVX with screw BMP group was highest, with a significant difference between the control and OVX with screw BMP groups (p<0.05). D : Tb.Sp of the control group was lowest. There was a significant difference between the control and OVX and OVX with screw groups (p<0.05), but there was no statistically significant difference between the control and OVX with screw BMP groups. A significant difference was evident between the OVX and OVX with screw BMP groups (p<0.05). *p<0.05 compared with control. †p<0.05 compared with OVX. BV/TV : bone volume/trabecular volume, OVX : ovariectomy, Tb.N : trabecular number, Tb.Th : trabecular thickness, BMP : bone morphogenetic protein, Tb.Sp : trabecular separation.

  • Fig. 8. Representative photographs of the H&E staining of the tibia. Disappearance of the bony trabeculae and increased of adipose tissue proportion at the bone marrow in the OVX, OVX with screw and OVX with screw BMP groups were apparent compared with the control group. Although not to the level of the control group, this condition was better than in the OVX with screw BMP group. In the bone lamellae in direct contact with the screw, there were more extensive and thickened trabecular bone around the implant in the OVX with screw BMP group than the OVX with screw group (Magnification, ×20). A : Sham (control) group, B : OVX-induced osteoporosis group, C : OVX and biodegradable screw (OVX with screw) group, D : OVX and BMP-2 containing biodegradable screw (OVX with screw BMP) group. OVX : ovariectomy, BMP : bone morphogenetic protein.

  • Fig. 9. Representative photographs of Masson’s trichrome staining. Mineralized collagen around the contact area of the screw appeared most prominent and most organized in the OVX with screw BMP group (magnification, ×20). A : Sham (control) group, B : OVX-induced osteoporosis group, C : OVX and biodegradable screw (OVX with screw) group, D : OVX and BMP-2 containing biodegradable screw (OVX with screw BMP) group. OVX : ovariectomy, BMP : bone morphogenetic protein.


Reference

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