The pathophysiology of tissue necrosis following cryotherapy has been determined. Liquid nitrogen is the most effective cryogen but it has not gained widespread acceptance in the medical community. There are a number of locally recurrent intraosseous lesions of the mandible where the recurrence rate after local enucleation is unacceptably high and a modality is required which could devitalize any remaining pathological cells on the periphery of a lesion to decrease the incidence of recurrence. It is hypothesized that liquid nitrogen cryotherapy can devitalize cells in the periphery of a bone cavity and that the osteogenic process will revitalize the bone and obliterate the bone cavity, augmented by bone marrow grafting if indicated.
The specific aims of this study are: 1) to determine the width of the zone of devitalized bone caused by controlled use of liquid nitrogen cryotherapy around a mandibular bone cavity; 2) to assess healing of the bone cavity which has been treated by liquid nitrogen cryospray; 3) to assess the healing of the bone cavity following liquid nitrogen cryospray treatment and simultaneous bone grafting (specific aims #2 and #3 will assess the rate of bone healing, the pattern of bone healing and the effects of cavity size on bone healing with and without simultaneous bone grafting); 4) to assess the effects liquid nitrogen cryospray on the dental pulp and periodontal tissues. Utilizing the mini pig animal model, standardized 2 cm, 4 cm, and 6 cm cavities will be created in the mandible. All cavities except controls will receive cryotreatment by either a cryoprobe technique or a cryospray technique with thermocouple monitoring. In addition, one-half of the cavities will receive simultaneous bone grafting following the cryosurgery treatment. Some animals will be sacrificed at three days to enable the extent of necrosis around the cavity to be measured. Temperatures achieved will be recorded on thermocouples and the width of necrosis evaluated by objective histological criteria. The remaining animals will be sacrificed at three months to assess the rate of healing of the cryotreated cavities. Assessment of the rate of bone healing will be by objective measurement of standardized histological preparations, vital double-label staining with tetracycline derivatives, immunohistochemistry for proliferating cell nuclear antigen and digital subtraction radiography. This study will determine: 1) the temperatures reached and width of necrosis around a cryotreated therapy when liquid nitrogen is applied by means of a) a cryoprobe and b) a cryospray; 2) the rate of bone healing in a cryotreated cavity as compared with a noncryotreated cavity; 3) the effect of cavity size on the rate of healing; 4) the effect of simultaneous cancellous bone grafting on the rate of healing. This will determine if there is a critical cavity size above which simultaneous bone grafting is indicated; 5) by examination of the teeth adjacent to the cryotreated cavities, the effects of the cryotreatment will be determined. Teeth and periodontal membranes will be examined utilizing objective histological criteria. The results of this study will be used as preliminary data for a wider ranging study of the effects of liquid nitrogen cryotherapy on bone.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE011189-01
Application #
2132363
Study Section
Special Emphasis Panel (ZDE1-PW (19))
Project Start
1994-09-30
Project End
1996-09-29
Budget Start
1994-09-30
Budget End
1996-09-29
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Dentistry
Type
Schools of Dentistry
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Pogrel, M A; Regezi, J A; Fong, B et al. (2002) Effects of liquid nitrogen cryotherapy and bone grafting on artificial bone defects in minipigs: a preliminary study. Int J Oral Maxillofac Surg 31:296-302