2017 ISAKOS Biennial Congress ePoster #1117

 

Thermal Hydrogel Loaded With Estradiol Promotes Graft Bone Healing After Anterior Cruciate Ligament Reconstruction With Artificial Ligament

Fang Chai, MD, Shanghai CHINA
Fang Wan, MD, PhD, Shanghai CHINA
Jia Jiang, MD, PhD, Shanghai CHINA
Shiyi Chen, MD, PhD, Prof., Shanghai CHINA

Huashan Hospital affiliated to Fudan University, Shanghai, Shanghai, CHINA

FDA Status Not Applicable

Summary

A drug control releasing system, namely thermal hydrogel loaded with estradiol, is capable in promoting graft bone healing process after anterior cruciate ligament reconstruction with artificial ligament.

Abstract

Background

newly invented thermal hydrogel, renowned for its biocompatibility as well as phase changing ability on different temperatures, enables long time drug releasing in vivo. Estradiol is crucial in bone metabolism, affecting bone formation and degeneration in previous research. We loaded the estradiol with thermal hydrogel to test whether it may promote graft bone healing in ACL reconstruction animal model with PET ligament.

Methods

Thermal hydrogel with estradiol loaded was prepared and drug release curve was reached in vitro. In an in vivo study, we performed ACL reconstruction with PET artificial ligament fabricated with LARS artificial ligament remnant in 48 New Zealand rabbits. The rabbits were divided into four groups with 12 rabbits in each group: control group (C), hydrogel group (H), drug loaded hydrogel group (D), and estradiol (E) group. Rabbits in group H and group D received hydrogel injection into the bone tunnel immediately after ACL reconstruction. Rabbits in group E take subcutaneous injection of estradiol every 3 day after surgery, while group C take equivalent normal saline at the same time. Serum estradiol level were measured every other week after surgery. One thirds of the rabbit at 4 weeks, 8 weeks and 12 weeks were sacrificed separately for further study, including Micro-CT for bone volume and mineral density analysis, biomechanical tests on ultimate failure load and stiffness, histology study with use of hematoxylin and eosin stain and Masson’s trichrome stain.

Results

in the in vitro study, the drug release curve demonstrated consistent estradiol release at effective dose through 8 weeks during test. In the in vivo study, serum estradiol concentration goes up over time in group E and D while group C and H's results stay still. Further analysis revealed more steady concentration value in group D. Micro-CT results at 8 and 12 weeks after surgery shows increase in bone density in both group D and E which cannot be matched in group C and H. At 12 weeks after surgery, the diameter of group D is smaller than that of group E (P<0.05). Biomechanical test found greatest ultimate load and stiffness in group D compared with group E, C and H at 12 weeks after surgery. HE and Masson staining demonstrate the scar tissue thickness is smaller in both group D and E compared with group C and H at 8 weeks and 12 weeks (P<0.05). Moreover, new bone tissue formation can be found in group D and E via Masson staining, reflecting bone formation in the interface.

Discussion

our research indicated that estradiol may promote bone formation in graft healing period after ACL reconstruction. Uses of estrogen in bone formation research have been reported before, but its use in tendon to bone interference healing research lacks reports. Thermal hydrogel provided consistent drug release with steady concentration, which proved to be beneficial in graft bone healing process.

Conclusion

thermal hydrogel loaded with estradiol promotes graft bone healing after anterior cruciate ligament reconstruction with artificial ligament