BMP-2 within CAD/CAM customized bilaminar resorbable mesh promote cranial defect bone healing
James P. Bradley, M.D., Henry K. Kawamoto, MD, DDS, Hurig Katchian, BA.
University of California, Los Angeles, Los Angeles, CA, USA.
For repair of cranial vault defects, alloplastic (titanium or methylmethacrylate) solutions may result in nonhealing or infectious complications and autogenous solutions (split rib or calvaria) may result in excessive blood loss or donor site morbidity. As a new option, we investigated a method using a bilaminar resorbable construct with BMP-2 with hopes of providing initial structural support followed by bone healing without permanent foreign body problems. Our objective was to characterize animal cranial defect healing with a bone tissue engineering option and compare this new method with other clinical cases.
Part I: Surgically created large cranial defects in 40 day old Sprague Dawley rats were treated with 1) BMP-2 on a resorbable matrix within bilaminar resorbable plates, 2) transfected (hoct4, hcmf4c, hsox2, hklf4) adipose-derived stem cells (ASCs) seeded in collagen within bilaminar resorbable plates, 3) regular ASCs seeded in collagen within bilaminar resorbable plates, 4) bilaminar resorbable plates only or 5) nothing (control) (n=30). Osteogenic potential of transfected ASCs were compared to ASCs. The impact and fracture stability of the resorbable construct was studied. For bone healing: histology and microCT scans were analyzed at 6, 12, 24 weeks. Part II: Clinical patients with moderate to large cranial vault defects who underwent reconstruction from 2000-2007 were studied with CT scans in perioperative and follow-up (>6 months) (n=69). New method of BMP-2 in collagen sandwiched in a bilaminar resorbable construct fashioned from a CAD/CAM patient specific negative was compared to other methods.
6 months) (n=69). New method of BMP-2 in collagen sandwiched in a bilaminar resorbable construct fashioned from a CAD/CAM patient specific negative was compared to other methods. >RESULTS:
Part I: Transfected ASCs had 5-25 times greater bone marker expression than regular ASCs when in cultured in osteogenic media. The stability of bilaminar resorbable constructs was less than bone but greater than mesh. Rat cranial vault defects healed 85% faster and with 24% more final bone fill with BMP-2 or the transfected ASCs in the bilaminar constructs than the regular ASCs or construct only groups and had 55% more bone fill compared to the nothing (control) group. Part II: Clinical cranial defect reconstruction included 1)titanium mesh plate=11, cryopreserved bone flap=18, 3)patient specific alloplast=13, 4)split autogenous bone=19 and 5)new method of BMP-2 in bilaminar resorbable construct=8. Perioperative data showed higher complications with titanium mesh, frozen bone and alloplast with regard to infection and/or exposure (36%, 22% and 23% compared to autogenous= 5%, BMP/bilaminar construct= 14%). Bone healing was superior in the BMP/bilaminar construct and autogenous bone groups with complete bone healing in 85% and 90% compared to the others (frozen bone=18%, others=minimal healing).
CONCLUSION:1) BMP-2 or transfected ASCs within bilaminar constructs augmented bone healing of animal cranial defects; 2) a new method of treatment of large clinical cranial defects with BMP/bilaminar resorbable constructs provided improved bone healing with less infectious/exposure related problems over alloplastic options. This study documents our group’s experience with a bone tissue engineering approach for initial sturctural stability followed by bone healing without residual foreign body.