الفهرس 
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Abstract
Bone is the second most commonly transplanted tissue after blood. Biomaterials scaffold as implanted material promotes bone healing alone or in combination with other material(s), through osteogenesis, osteoinduction, and osteoconduction, in combination or alone. Bone tissue is a composite material composed by a combination of mineral phase (hydroxyapatite), organic components (collagen and proteins) and water. The proportion of these components may vary by age, gender, site and disease. Diseases, such as osteoporosis, and traumas can cause bone loss or bone fracture. Treatment of bone defects still is a challenge for orthopedic surgeons, especially for large ones.
Bioactive glasses (G) elaborated in the quaternary system SiO2–CaO–Na2O–P2O5 are potential candidates for bone repair and regeneration, and they have lately been successfully used in bone tissue engineering. Therefore, bioactive glass is osteoconductive besides its bioactivity, and it possesses inadequate desirable mechanical strength which makes it unable to support implant bearing load. Bioglass-Chitosan (BG-CH) contained a high rate of porosity approximatly 75 - 81% that can play an important role of vascularization.
Risedronate is an effective and well tolerated novel bisphosphonate that is suitable for first-line therapy in Paget’s disease. The rapid and sustained reductions in vertebral fracture incidence and BMD changes seen in patients with postmenopausal and glucocorticoid-induced osteoporosis indicate the drug to be a valuable treatment option with first line potential, particularly in patients for whom hormonal therapy is inappropriate.
The aim of this experimental study is to investigate the osteoconductive property and efficacy of bioactive glass combined with residronate sodium drug in repairing surgically created bony defects in the mandible. The assess of Biochemical parameters reflectie the effect of hybrid Bioactive chitosan - glass graft on bone remodeling in mongrel dogs as follows: by observations of bone formation and assessment of density changes through comparison of both test and control animals.
To fulfil this aim, Twenty mongrel dogs (Canis familiaris) were used. The selected dogs were apparently normal with an average weight of 20-30 kgs and average age of 1.5 years. The selected animals were quarantined in separate cages in the department of Veterinary Surgery, Faculty of Veterinary Medicine, Cairo University. Animals were divided into four equal groups. group (1): CH.PVA with no BG. (Non-Medicated), group (2): CH.PVA with no BG, (Medicated), group (3): CH.PVA with BG. (Non- Medicated), group (4): Chitosan Poly Vinyl Alcohol (CH.PVA) with Bioactive Glass (BG). (Medicated by Residronate Sodium Drug). We determined the levels of serum VEGF, BMP-2, Alk.Phos., Calcium, Phosphorus, Osteocalcin, Calcitonin.
At Gp1 (CH)(NM), the experimental side showed The defect appears clearly as well defined radiolucency with a radio-opaque surrounding normal bone. Also, at Gp2 (CH)(M), the experimental side showed the defect still radiolucent with some degree of bone formation. Also, at Gp3 (CH.BG)(NM), the experimental side showed the faint radio-opacity of the defect. Finally, at Gp4 (CH.BG)(M), the experimental side showed the defect in the right side of the mandible obliterated with the newly formed bone after 3 months. We noted, a homogenicity of the radiodensity of the bone of the mandible with the newly formed bone.
Biochemical analysis revealed that there was significant differences were observed in the calcium levels among (CH.BG) (NM) and (CH.BG) (M) groups when compared to (CH)(NM) group. While (CH)(M) group showed significant difference in the first and last two weeks of the study when compared to (CH)(NM) group, because of a high level of plasma calcitonin and the inhibition of osteoclastic resorption. Also, The current serum phosphorus level showed significant increase in (CH) (M) and (CH.BG) (NM) groups when compared to control group (CH)(NM). While a significant decrease in serum phosphorus level was recorded in the first five weeks followed by increase in (CH.BG) (M) group compared to control group (CH) (NM) with a (P value ≤ 0.05).
There was significant increase in serum ALP activity in (CH)(M) group when compared to control group (CH) (NM). While there was a non-significant difference in serum ALP activity in (CH.BG) (NM) when compared to control group (CH) (NM). Also, there was a significant difference in serum alkaline phosphatase activity in (CH.BG) (M) group when compared to the control group (CH) (NM) among study weeks with a (P value ≤ 0.05). Increase in serum alkaline phosphatase level may be due to increased chondroblastic proliferation to cause bone formation during fractured bone repair and also maximum contribution was from the periosteum of destructed bone which was a rich source of serum alkaline phosphatase.
Also, there was significant difference in serum calcitonin level in (CH)(M) and (CH.BG) (NM) groups when compared to control group (CH)(NM). Also, (CH.BG) (M) group showed significant difference in serum calcitonin level among most weeks when compared to (CH)(NM) group. Calcitonin lowering of blood calcium by its action on bone with inhibition of bone resorption or occure inhibition of osteoclastic activity and enhances bone formation. Also, There was a significant difference in serum OC level in the (CH)(M) and (CH.BG)(NM) groups when compared to control group (CH)(NM) among weeks. Also, there was a significant decrease in serum OC level in the (CH.BG) (M) when compared to control group (CH) (NM). Because osteocalcin considered to be an osteoblast related marker of bone formation.
There was a non-significant decrease in serum VEGF level in the (CH) (M) group when compared to control group (CH)(NM) only at 3 weeks (P-value > 0.05). While, there was a non-significant decrease in serum VEGF level in the (CH.BG) (NM) group when compared to (CH)(NM) only at 2 weeks (P-value > 0.05). There was a significant decrease in serum VEGF level in the (CH.BG)(M) when compared to control group (CH) (NM) during 4,5,8,9,11,12 weeks (P-value ≤ 0.05). Highly significant increase was observed in serum BMP-2 activity in the (CH.BG)(M) group when compared to other groups with a (P value ≤ 0.05). The implantation of the matrix four weeks before BMP application resulted in the weakest ossification and indicated that tissue already formed around the implant might have reduced the ability of applied BMP-2 to recruit mesenchymal progenitor cells from the surrounding to stimulate bone formation.
Based on the results of this study, it can be concluded that :
1. Biocomposite scaffold can show comparable osteogenic ability in the presence of risedronate as added medication.
2. The data suggest that the biocomposite is a promising candidate for using it as a scaffold in tissue engineering of bone. Large normal osseous defect resulted post surgically could be effectively and safely obliterated with this scaffold material without any complication.
3. scaffold has no allergic or cyto-toxic reaction, so it can be widely used on bone surgery as a space maintained material.
4. This study demonstrated the feasibility of using the biochemical reaction as an earlier indication for bone healing in comparison with x-ray as histopathological examination.
Recommendations
VIII. Recommendations
1. Further clinical studies are needed to find a predictable way to ensure success and more futuristic application of the scaffold (chitosan- bioactive glass- risedronate) in large bone cavities in the human studies.
2. The scaffold are urged to speed cellular generate bone and reformulated to bones tinny regularly.
3. The blood biochemical tests can be used as an earlies indicator for the newly formed bones.
4. Therefor and according to the obtained results it is very important to find a correlationship between the blood biochemical changes of minerals, growth factors, enzymes and bone components during the osteogenesis and the time elapsed. In addition to find relationship between the histological findings and the liberated bone markers in the blood during the healing process, in order to evaluate the quality of the newly regenerated bone.
5. serum biochemical markers as a clinically useful tool to monitor early changes in bone formation before radiographic signs of bone healing. The study also demonstrated that bioactive glass in combination with chitosan and residronate provided optimum
6. tissue guiding for regeneration of surgically created mandibular defects in dog model. Such combination provided accelerated bone healing compared to other groups with reducing the time required for optimum healing.