[Study on in vivo drug delivery and repairing large segmental infected bony defect with massive reconstituted bovine xenograft aided by calcium phosphate cement drug core].
OBJECTIVE
To find out an effective technique to repair large segmental infected bony defect.


METHODS
Calcium phosphate cement (CPC) incorporated with bone morphogenetic protein and gentamycin was embedded in the massive reconstituted bovine xenograft (MRBX), then CPC-MRBX was obtained after CPC's solidification. In vivo test was applied to test the drug delivery capability of CPC-MRBX, in which it was implanted in the dorsal muscle pouch of 18 rabbits. The drug concentration of animal blood and surrounding soft tissue of the CPC-MRBX in the muscle pouch was measured 1, 2, 5, 10, 15, 20, 25, 30 and 35 d after operation, 2 rabbits each time. Large segmental infected femur defect in the rabbit model was created to test the repairing capability of CPC-MRBX. External fixation was done 1.5-2.0 cm above the knee, the most adjacent nail to fracture site was 0.5-0.8 cm away, and proper pressure was applied to the graft. In experimental group (n = 25), the bony defect was replaced by CPC-MRBX, while in the control group(n = 15) dissected bone block was re-implanted in original position. The animal was subjected to radiographic, histological examination at 4, 8, 16 and 24 weeks. The general condition was observed after the operation.


RESULTS
CPC-MRBX was easily made under normal temperature and pressure. In vivo drug delivery test showed that the drug concentration of the tissue remained above the minimal inhibitory concentration of staphylococcus 30 d after operation and no significant increase of blood drug concentration was observed. In experimental group, no adverse influence was observed. Four weeks after operation, the animal could bear load, bony callus around the graft was observed by X-ray, and abundant chondral tissues that grew into CPC-MRBX were observed by histological method. Eight weeks after operation, progressively increasing bony callus around the graft was observed, external fixation could be removed, normal function was restored, and CPC was degenerated dramatically while new bone tissues were growing. Sixteen weeks after the operation, more new bone tissues grew and CPC was degenerated further while marrow tissues were taking shape. Twenty-four weeks after the operation, femur healed completely and CPC was degenerated completely. In the control group, the autograft remained unhealed on X-ray at 4 weeks, and osteomyelitis manifestation such as inflammatory cells infiltration and osteolysis was detected at 4 weeks. All the animals in the control group died before the 8th week, 4 of which showed positive hemoculture.


CONCLUSIONS
CPC-MRBX is readily available and can be applied to repairing large segmental infected bony defect.
Sun
Xiaotang
X
Department of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an Shaanxi, 710032, PR China.
Zhao
Li
L
Hu
Yunyu
Y
Du
Junjie
J
Yuan
Zhi
Z
Cui
Geng
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001843:Bone Cements / Q000737:chemistry*; D001850:Bone Diseases, Infectious / Q000382:microbiology / Q000601:surgery*; D018786:Bone Substitutes; D016025:Bone Transplantation / Q000379:methods*; D002130:Calcium Phosphates / Q000737:chemistry*; D002417:Cattle; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000382:microbiology / Q000601:surgery; D005839:Gentamicins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits; D013203:Staphylococcal Infections / Q000601:surgery; D014183:Transplantation, Heterologous
D000900:Anti-Bacterial Agents; D001843:Bone Cements; D018786:Bone Substitutes; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D005839:Gentamicins; C020243:calcium phosphate