Injectable And Thermoreversible PCLA-PEG-PCLA Hydrogel As A Barrier For Prevention Of Tendon Adhesion In Rabbits

BackgroundThe tendon adhesion after injury or operation is a kind of serious complication and induces the motor dysfunction of tendon [1]. Former experiment revealed that the biodegradable thermoreversible triblock (PCLA-PEG-PCLA)hydrogel was highly effective in preventing post-operative intestinal adhesion [2]Thus, we hypothesize that the biodegradable thermoreversible triblock (PCLA-PEG-PCLA) hydrogel could prevent tendon adhesion in rabbits.MATERIALS and METHODS:Fifty four New Zealand White rabbits, which average weight was2.50kg, were selected as experiment animals. Their2nd and4th flexor digitorum profundus tendons of the left forepaw were subjected to a standard "shaving" surgical injury [3]and proximal unloading tenotomy of the flexor tendons [4]. All animals were randomly divided into3groups:A, PCLA-PEG-PCLA Hydrogel Group, B, Hyaluronan Gel Group and C, Saline Group. The defects were treated by PCLA-PEG-PCLA hydrogel, hyaluronan gel or saline respectively. Animals were subjected to euthanasia and different analyses1week,3weeks and6weeks after operation.Morphological Assessment:Operation site of Digit2was dissected. The macroscopic grading of the peritendinous adhesions were evaluated by double blind method. After amputated, joint range of motion was measured. All digit-tendon complexes were fixed in4%formalin and then sent to double-blinded histology assessment by HE staining.Biomechanical Tests:To assess gliding function, simulated passive flexion (the angular motion of the distal interphalangeal joint) of2nd digits was measured. To assess adhesion formation, the maximum pull-out force of4th digits was measured. The2nd or4th digits of tight forepaws were randomly chosen as the negative control (Group D). The statistical analyses were performed the experimental groups.Results:Morphological Assessment:1, Macroscopic evaluation:The macroscopic grading of the peritendinous adhesions showed A<B<C1week after operation, however, there was no statistically significant difference among the three groups (P>0.05) The macroscopic grading of the peritendinous adhesions showed B<A<C three weeks after operation, and the peritendinous adhesion in Group B is significantly slighter than in Group C (P<0.05). Moreover, the macroscopic grading of the peritendinous adhesions showed C<B<A6weeks after ooperation, however, there was no statistically significant difference among the three groups (P)0.05).Histological Evaluation:1) The grading of the peritendinous adhesions asessments:At1、3、6weeks postoperatively, the grading of the peritendinous adhesions were A<B <C, A<B<C and C<B<A respectively, however, there were no statistically significant difference among the three groups (P)0.05)2) Inflammatory reaction assessment:At1、3weeks postoperatively, the grading of inflammatory reaction were A<C<B and A<B<C, however, there were no statistically significant difference among the three groups (P)0.05). At6weeks postoperatively, the inflammatory reaction in Group A and C disappeared. There are minimal inflammatory cells infiltration into fibroosseous tendon sheath in Group B, however, there were no statistically significant difference among the three groups (P)0.05)Biomechanical Tests:1) Maximum pullout force measurement:At1week postoperatively, the mean peak pullout force required to break the adhesion were A (1.211±0.472N) <B(1.553±1.140N)<C(2.198±1.122N), however, the difference among three groups were not statistically different. At3weeks postoperatively, the mean peak pullout force were C(2.311±0.305N)<A (3.680±1.139N)<B (4.231±1.097N), the difference between Group B and C was statistically different (P<0.05). At6weeks postoperatively, the mean peak pullout force were A(2.353±0.845N)<C(2.870±1.296N)<B(4.351±2.106N), however, the difference among three groups were not statistically different.(P>0.05). At1、3、6weeks postoperatively, difference between Group C and D were statistically significant (P<0.05)2, Simulated passive flexion:At1、3、6weeks postoperatively, the mean peak simulated passive flexion were B (90.875±1.031°)>A (89.167±7.607°)>C(86.200±4.494°), B(84.800±5.155°)>C (80.000±5.100°)>A (78.500±5.579°) and C (67.667±15.044°)>A (63.333±5.774°)>B (55.667±12.897°), however, the difference among three groups were not statistically significant (P>0.05). At1、3、6weeks postoperatively, difference between GroupC and D were all statistically significant (P<0.05)Conclusions:A standard "shaving" surgical injury and proximal unloading tenotomy of the flexor tendons resulted in tendon adhesion in rabbits. This animal model was stable and repeatable.The biodegradable thermoreversible PCLA-PEG-PCLA hydrogel has good biocompatibility.During the first3weeks postoperately, the biodegradable thermoreversible PCLA-PEG-PCLA hydrogel may have a potential effect on preventing tendon adhesion and inflammatory reaction in rabbits.