The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament. An in vivo study.
We report a biologic approach to improve medial collateral ligament healing using growth factors normally expressed in healing tissue. Our previous in vitro work demonstrated that platelet-derived growth factor-BB and transforming growth factor-beta 1 promoted fibroblast proliferation and matrix synthesis, respectively. There-fore, these growth factors were used in vivo to determine whether they could improve medial collateral ligament healing, whether this effect was dose-dependent, and if combinations of growth factors could improve healing more than individual growth factors. Thirty-seven rabbits had various doses of growth factors applied to the ruptured right medial collateral ligaments using a fibrin sealant delivery vehicle. The five groups consisted of 1) two groups receiving two doses of platelet-derived growth factor-BB, 2) two groups receiving two doses of this growth factor plus transforming growth factor-beta 1, and 3) one group receiving fibrin sealant only. After sacrifice at 6 weeks, biomechanical and histologic evaluations of the healing ligament were performed. Femur-medial collateral ligament-tibia complexes of the knees given the higher dose of platelet-derived growth factor-BB had ultimate load, energy absorbed to failure, and ultimate elongation values that were 1.6, 2.4, and 1.6 times greater than the same complexes of the control group. Adding transforming growth factor-beta 1 did not lead to any further increase in the structural properties of the complex compared with treatment with platelet-derived growth factor-BB. These encouraging results suggest that use of platelet-derived growth factor-BB may improve the quality of the healing medial collateral ligament, and that it may also have a similar potential for promoting healing of other ligaments.
Department of Orthopaedic Surgery, University of Pittsburgh, Pennsylvania 15213, USA.
K A
KA
Hildebrand
S L
SL
Woo
D W
DW
Smith
C R
CR
Allen
M
M
Deie
B J
BJ
Taylor
C C
CC
Schmidt
D000704:Analysis of Variance; D000818:Animals; D000077214:Becaplermin; D001696:Biomechanical Phenomena; D002455:Cell Division / Q000187:drug effects; D017885:Collateral Ligaments / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage / Q000627:therapeutic use; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D007718:Knee Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008934:Mitogens / Q000008:administration & dosage / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D020574:Proto-Oncogene Proteins c-sis; D011817:Rabbits; D011994:Recombinant Proteins; D012421:Rupture; D013718:Tensile Strength; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use; D016474:Weight-Bearing / Q000502:physiology; D014945:Wound Healing
D004338:Drug Combinations; D015718:Fibrin Tissue Adhesive; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000077214:Becaplermin; D004815:Epidermal Growth Factor