Journal of Orthopaedic Research 23 (2005) 274-280

Journal of Orthopaedic

Research www.elsevier.com/locate/orthres

The effect of shock wave treatment at the tendon-bone interface- an histomorphological and biomechanical study in rabbits

Ching-Jen Wang a, Feng-Sheng Wang b3*, Kuender D. Yang b,

Lin-Hsiu Weng a, Yi-Chih Sun b, Ya-Ju Yang a Department of Orthopedic Surgery, Chang Gung Memorial Hospital Medical Center, Kaohsiung, Taiwan

Department of Medical Research, Chang Gung Memorial Hospital Medical Center, Kaohsiung, Taiwan

Received 24 November 2003; accepted 19 July 2004

Abstract

Purpose. This study was performed to investigate the effect of shock wave treatment on the healing at tendon-bone interface in rabbits.

Materials and methods. Thirty-six New Zealand White rabbits were used in this study. The anterior cruciate ligament was excised and replaced with the long digital extensor. The right knees (study group) were treated with 500 impulses of shock waves at 14kV, while the left knees (control group) received no shock waves. Histomorphological studies were performed in 24 rabbits at I , 2,4, 8, 12 and 24 weeks. Biomechanical studies were performed in 12 rabbits at 12 and 24 weeks.

Results. There was significantly more trabecular bone around the tendons noted in the study group compared with the control group at different time intervals after 4 weeks (P < 0.05). The contacting between bone and tendon was significantly better in the study group than the control group after 8 weeks (P < 0.05). The tensile strength of the tendon-bone interface was significantly higher in the study group than the control group at 24 weeks (P = 0.018), whereas similar modes of graft failure were noted between the two groups.

Conclusion. Shock wave treatment significantly improves the healing rate of the tendon-bone interface in a bone tunnel in rab- bits. The effect of shock waves appears to be time-dependent. 0 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Introduction and background

Ligament reconstruction of the knee is one of the most common surgical procedures and usually is per- formed by the implantation of a tendon graft in a bone tunnel. The success of ligament reconstruction relies upon the firm healing of tendon to bone. Despite the improvement in fixation techniques with new surgical devices, the healing of a tendon graft to bone remains

* Corresponding author. Tel.: +886 7 733 5279; fax: +886 7 733

E-mail address: w28121 l@adm.cgmh.org.tw (F.-S. Wang). 5515.

unclear. Some studies described ligamentization after implantation of a tendon graft in a bone tunnel [ 1,3,4,16,3436], whereas other studies showed the oppo- site results, and concluded that bone and tendon do not heal together [6,13].

The complex healing and remodeling processes of a tendon graft depend upon a variety of factors including the application of mechanical forces to the grafts [1,19- 221. Recently, shock wave treatment has been shown to be effective in the treatment of certain musculoskeletal disorders including chronic non-union of long bone fracture [23-271, and tendinopathies of the shoulder, elbow and heel [7,18,28,29]. In animal studies, shock wave treatment was shown to increase cortical bone forma- tion in acute fracture [29] and induce neovascularization

0736-0266/$ - see front matter 0 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. doi: 10.10 1 6/j.orthres .2004.07.004

C.-J. Wang et al. I Journal of' Orthopaedic Research 23 (2005) 274-280 275

and improvement of blood supply at the bone-tendon junction [31,32]. We hypothesized that shock wave treat- ment may enhance tendon healing to bone. The purpose of this study was to investigate the effect of shock wave treatment on the healing at the tendon-bone interface in rabbits.

Materials and methods

Study model and animal

The Institutional Review Board of our hospital approved this study, and the study was performed under the guidelines and the care and use of animals in research. Thirty-six New Zealand White rabbits of 12 months old with body weight ranging from 2.79kg to 3.65kg were used in this study. Twenty-four rabbits were used for histomor- phological study, and 12 rabbits for biomechanical study. With the rabbit anesthetized with ketamine (50mglkg) and phenobarbital (50mg/kg), both lower limbs were shaved and scrubbed and prepared with sterile technique. Arthrotomy of the knee was carried out through a medial parapatellar approach. The anterior cruciate ligament was ex- cised. The long digital extensor tendon was dissected off distally at the musculotendinous junction while the proximal femoral attachment was left intact. The tihial tunnel was created with a graft size-matched drill bit through the anterior cruciate ligament footprint, and exited on the anteromedial aspect of the proximal tibia. The distal end of the graft was re-routed intra-articularly and pulled into the tibia tunnel and se- cured to bone through drill holes with Ethibond sutures with the knee at 30" of flexion (Fig. 1). The surgery mimicked anterior cruciate liga- ment (ACL) reconstruction using long digital extensor tendon graft. This study was designed to focus only on the tibial tunnel. Therefore, the proximal end of the graft was left intact and no femoral tunnel was made. The knee joint was irrigated and closed in routine fashion. Post- operatively, the knee was covered with a bulky dressing with no addi- tional immobilization. The animal was returned to the housing cage and was cared for by a veterinarian. Prophylactic antibiotic with amp- icillin 50mgIkg was given intramuscularly for 5 days. The general activities of the rabbits and the local wound condition were inspected daily.

Fig. 1. A sketch showed the surgical technique of tendon reconstruc- tion by intra-articular transplantation of the distal end of the long digital extensor into the tibial tunnel.

Shock wave application

The left knees received no shock wave treatment, and were used as the control group. The right knees received shock wave treatment, and were regarded as the study group. Shock waves were applied immedi- ately after surgery. The source of shock waves was from an Ossa-Tron orthotriptor (High Medical Technology, Kreuzlinger, Switzerland). The shock wave was focused on the mid-portion of the tibial tunnel with the control guide of the device, and the depth was estimated clini- cally and determined with an ultrasound guide. Surgical lubricate was applied to the area of skin in contact with the shock wave tube. Each rabbit was treated with 500 impulses of shock waves at 14kV to the right knee. The optimal dose of shock waves so chosen was based on our previous experience in animal experiments [8,33]. Immediately after shock wave application, the right knee was examined for swelling, ecchymosis or hematoma etc. There was no device-related problems, systemic or local complications.

Histomorphological assessment

Twenty-four animals were sacrificed at different time intervals with four rabbits each at 1, 2,4, 8, 12 and 24 weeks. The middle 113 of the tibial tunnel were dissected and fixed in 4% PBS-buffered paraformal- dehyde for 48h and decalcified in PBS-buffered 10% EDTA. Decalci- fied tissues were embedded in paraffin. Specimens were cut transversally into 5 p thick sections and transferred to poly-lysine- coated slides for conventional hematoxylin+osin, alcian blue or aliza- rin red staining (Sigma Chemicals Inc, St. Louis, MO, USA) to distin- guish fibrous, cartilaginous and bony tissues as previously described [1,2]. Five regions within the specimens from three sections obtained from each specimen were randomly selected (Fig. 2) using a Zeiss Axi- oskop 2 plus microscope (Carl Zeiss, Gottingen, Germany). Three ran- dom images of 0.75mm2 from each area (3mm2) were then taken under 400x magnification. All images of each specimen were captured using a Cool CCD camera (SNAP-Pro c.f. Digital kit; Media Cybernetics, Sli- ver Spring, MD, USA). Images were analyzed using Image-Pro@ Plus image-analysis software (Media Cybernetics, Sliver Spring, MD, USA). Percentages of fibrous tissue, cartilaginous tissue, fibrocartilage and bony tissue were calculated. Fibroblasts, chondrocytes and osteo- blasts were identified morphologically.

Previous studies have demonstrated that graft incorporation is bone specific [12,14,15]. We sought to elucidate the effect of shock wave on the direct contact between the hone tunnel and grafted ten- don. After alizarin red staining, the positive staining area directly sur- rounded the grafted tendon were captured under 50x magnifications. Contact angle were calculated the total contact angle within 360" circle around the grafted tendon. A pathologist, blinded to the treatment regimen, performed measurements on all sections under 400x mag- nification.

Fig. 2. Schematic view of counting area between grafted tendon and tibial tunnel. After hematoxylin-eosin, alcian blue or alizarin red staining, areas of fibrous, cartilaginous or bony tissues in each of these 5 areas (shadowed boxes) were counted after using 40x magnification.

276 C.-J. Wang et at. I Journal of Orthopaedic Research 23 (2005) 274-280

20

16 Shock waves

5 12

s v

9 8

4

0.00 0.20 0.40 0.60 0.80 1 0

0 (A) cs) EXTENSION (In)

Fig. 3. The measurement of tensile strength of the tendon graft was performed on MTS (material testing system) machine (A). The load distraction curve of the tendon graft showed significantly higher peak load in the study group with shock wave treatment than the control group at 24 weeks (B).

Tensile strength test Table 1 The effect of shock waves on the trabecular bone around the tendon

Twelve rabbits were sacrificed with six rabbits each at 12 and 24 weeks. The knee joint including the femur, the tibia and the tendon graft was obtained, and the remaining structures were removed. The tensile strength of the tendon graft was measured with Material Test- ing Machine (MTS system, Minneapolis, MN). Both femur and tibia bones were fixed with bone clamps attached to the machine. The tensile strength of the tendon graft was measured by a slow distraction of the machine, and the peak load was determined when graft failure oc- curred (Fig. 3A and B). The sites of graft failure and the modes of fail- ure including graft pullout from the bone tunnel, rupture in the graft substance and avulsion fracture at the tendon-bone junction were carefully examined. The MTS tests were similarly performed in the study and control groups.

Shock waves Control P-value'

1-week mean f SD 18.2 ? 3.3% 20.1 f 4.3% 0.98 2 weeks mean f SD 22.6 f 3.8 23.7 f 3.8 0.87 P-value 0.53 0.69

4 weeks mean ? SD 32.9 2 2.8 25.7 f 3.1 0.022 P-value 0.012 0.57

8 weeks mean f SD 34.9 2 3.7 26.8 f 3.2 0.015 P-value 0.01 1 0.38

Statistical analysis

The data at different time intervals were compared statistically with the baseline data at I week within the same group using non-paramet- ric ANOVA (Kruskal-Wallis) test, whereas the data between the study group and the control group were compared statistically using the Mann-Whitney test with statistical significance set at P < 0.05.

Results

Histomorphological studies

The effects of shock wave treatment on the trabecular bone in the surrounding tissues of the tendon are sum- marized in Table 1. The percentage of trabecular bone around the tendon graft increased significantly with time after 4 weeks in the study group ( P < 0.05), whereas, the changes in the control group were statistically not signi- ficant ( P > 0.05). The difference in the amount of trabe- cular bone around the tendon graft between the study and control groups was statistically significant at each time interval after 4 weeks. The microscopic features of trabecular bone around the tendon graft are shown in Fig. 4A and B for the study and the control group, respectively.

The effect of shock waves on the contacting between tendon and bone are summarized in Table 2. In the study group, the tendon graft was largely surrounded by trabecular bone with small areas of cartilage, and

12 weeks mean f SD 37.4 ? 4.1 28.3 f 2.2 0.017 P-value 0.019 0.47

24 weeks mean k SD 39.4 ? 3.2 27.6 f 2.4 0.023 P-value 0.008 0.41

The data represent the percentage of trabecular bone in the sur- rounding tissues around the tendon. P-value compared the data at different time intervals with baseline data at 1 week. P-values' compared the data between the study and control groups.

there was intimate attachment between tendon and bone and cartilage. In the control group, however, the tendon was surrounded primarily by fibrous tissue with very limited bone tissue, and the attachment between tendon and the fibrous tissues was very loose. The percentage of contacting between tendon and bone appeared to be time-dependent in both groups, but was more pro- nounced in the study group. The difference in the per- centage of contacting between tendon and bone was statistically significant between the study and control groups at each time interval after 4 weeks (P < 0.05). The microscopic features of bonding between tendon and bone are shown in Fig. 5A and C for the study group and Fig. 5B and D for the control group.

Tensile strength test

The results of tensile strength at the tendon-bone junction of the study and control groups are summarized

C.-J. Wung et (11. I Jvurnul of Ortkopurdic Resrurch 23 (2005) 274-280

(A) Shock wave (B) Control

277

Fig. 4. Histomorphological pictures in longitudinal section showed that the tendon graft was largely surrounded by bone tissue in the shock wave group (A). In the control group, the tendon graft was surrounded by fibrous tissue and limited fibrocartilage (B). Tn: tendon; Tb: trabecular bone; Cg: cartilage; Fs: fibrous tissue.

Table 2 The effect of shock waves on the contacting between bone and tendon

shock wave treatment improved the graft strength and resisted the graft pullout at the tendon-bone junction.

Shock waves Control P-value'

1 week mean f SD 92.6 f 16.6" 94.8 f 15.2" 0.73 2 weeks mean 2 SD 104.8 f 13.5" 105.6 f 14.9" 0.81 P-value 0.92 0.86 Discussion

4 weeks mean f SD 13 1.6 f 24.6" 1 14.8 f 20.2" 0.01 1 P-value 0.016 0.36

8 weeks mean f SD 243.6 f 25.3" 142.8 f 19.2" 0.01 1 P-value 0.006 0.017

12 weeks mean f SD 286.8 f 37.9" 173.2 f 22.8" 0.017 P-value 0.005 0.019

24 weeks mean f SD 304.8 f 23.6" 216.8 f 24.6" 0.IKM P-value <O.OOI 0.012

The data represent the degrees of contacting between tendon and bone within 360" circle around the tendon. P-value compared the data at different time intervals with the baseline data at 1 week. P-value' compared the data between the study and control groups.

in Table 3. The difference in the tensile strength between the study and control groups was statistically significant at 24 weeks ( P = 0.018); however, such difference was not statistically significant at 12 weeks ( P = 0.597). It appeared that the effect of shock wave treatment on the tensile strength at the tendon-bone interface is time-dependent. Moreover, increased tensile strength is associated with elevated tendon-bone contact at 24 weeks (r2 = 0.864).

Similar modes of mechanical failure of the tendon graft at the tendon-bone junction were observed, how- ever, different frequencies of graft failure were noted be- tween the two groups. Complete graft pullout from the bone tunnel was noted in all cases in the control group, whereas the modes of failure in the study group included graft pullout in 4, graft breakage in 1 and one avulsion fracture at the tendon-bone junction. It appeared that

The success of ligament reconstruction depends in part, on the healing of tendon graft to bone. Many studies have provided evidence that a tendon graft is incorporated into a bone tunnel by ossification or for- mation of a fibrous sleeve of callus [10,16,36]. Yet, very little is known about the character of the tendon-bone interface. Rodeo et al. [21] transplanted the proximal end of the long digital extensor into a bone tunnel at the proximal tibia in a dog model, and demonstrated that progressive healing of tendon into bone tunnel be- tween 8 and 12 weeks. The design of tendon graft in that study differed from that commonly used in clinical appli- cation because the tendon together with the muscle was used, and the graft was not subject to cyclic loading as it did not cross the knee joint. The healing process of a graft to bone under physiological loading condition may differ from a tendon-muscle unit not under loading [5]. Blickenstaff et al. [4] performed an intra-articular semitendinosus autograft in ACL reconstruction in rab- bits, and demonstrated that bony fixation occurred by the formation of an indirect tendon insertion at 26 weeks, and greater graft strength and stiffness than nor- mal semitendinosus tendon and the anterior cruciate ligament at 52 weeks.

In clinical practice, most ligament reconstructions of the knee are performed with a free tendon graft such as patellar bone-tendon-bone or hamstring graft, and the graft is under physiological cyclic loading of the knee joint in normal activities of daily living. The mechanism of healing of a graft to bone under physiological loading condition is unknown [3,5,9-11,16,17,22,36,37]. The remodeling processes of tendon graft depend upon a variety of factors [1,19-22,35,36]. Anderson et al. [l]

278 C.-J. Wang ef al. I Journal of Orthopaedic Research 23 (ZOOS) 274-280

Shock wave Control

Fig. 5. Histomorphological pictures in axial section at the mid-portion of the tendon-bone interface: (A) in shock wave group, the tendon was largely surrounded by trabecular bone; (B) in the control group, the tendon was surrounded predominantly by fibrous tissue and limited bone tissue; (C) in higher power view, the tendon was intimately attached to bone and cartilage in the study group and (D) in control section, the junction between tendon and bone was filled with fibrous tissue. Tn: tendon; Tb: trabecular bone; Cg: cartilage; Fs: fibrous tissue.

Table 3 The effect of shock waves on tensile strength and graft failure

Time Shock wave Control P-value'

12 weeks ( N = 6 ) (N = 6) Peak load (N)

Mode of failure Pullout 5 6 Breakage 1 0 Fracture 0 0

Mean f SD 52.69 f 22.02 46.72 f 8.8 0.597

24 weeks ( N = 6 ) (N = 6) Peak load (N)

Mean f SD 109.94 f 22.05 73.55 k 13.83 0.018 P-value 0.003 0.009

Mode of failure Pullout 4 6

Fracture 1 0 Breakage 1 0

Peak load in Newton represents the tensile strength when graft failure occurred. P-value compared the data at 12 weeks with 24 weeks. P-value' compared the data between the study and control groups.

tion with no graft pullout at 24 weeks, and the interference fit fixation is beneficial for tendon-to-bone incorporation by leading to the development of a direct type of ligament insertion due to direct-contact healing without the development of a fibrous interzone. Other studies have also shown that parathyroid hormone and physical factors such as CPM (continuous passive motion) could accelerate tissue healing of the joint including bone and cartilage [2,19,20].

The design of this study included an intra-articular tendon transplantation mimicking ACL reconstruction under physiological loading of the knee similar to that used in clinical application. The results of the current study demonstrated that physical shock waves signifi- cantly increased the trabecular bone around the tendon graft, improved the contacting between tendon and bone and enhanced the tensile strength at 24 weeks. The effect of shock wave treatment on the healing at the tendon-bone interface appeared to be time-depend- ent. The source of trabecular bone could be new bone formation from the native bone. The exact mechanism of shock waves remains unclear. The results of our pre- vious studies in animal experiments showed that shock waves promote bone formation and healing of segmen- tal femur defect associated with bone morphogenetic protein (BMP) expression in callus in rats [8,33], en- hance bone mass and bone strength after fracture in rab- bits [30] and induce neovascularization and improve

and Rodeo et al. [22] have shown that addition of osteo- inductive growth factors such as bone morphogenetic protein can improve the tendon healing in a bone tun- nel. Weiler et al. [35,36] performed ACL reconstruction with Achilles split graft and biodegradable screw fixa- tion in a sheep model, and showed excellent graft fixa-

C.-J. Wang et ul. I Jour~iul qf Orthopaedic Reseurch 23 (2005) 274-280 279

blood supply at the tendon-bone junction 131,321. Therefore, it is reasonable to assume that shock wave treatment stimulates the ingrowth of reactive bone for- mation associated with improvement in blood supply that leads to an increase in trabecular bone around the tendon and improvement in the contacting between ten- don and bone at the tendon-bone interface. Despite the benefits of shock waves, two third of the grafts failed as a result of graft pullout at 24 weeks. Based on the results of the study, cautious approach is recommended in returning patients to early full activities including sports after ACL reconstruction.

In conclusion, shock wave treatment significantly improved the healing of a tendon graft to bone in a bone tunnel in rabbits. The effect of shock waves on tendon- bone interface appeared to be time-dependent.

Acknowledgement

This study was supported by a grant from National Science Council of Taiwan (NSC 9 1-23 14-B- 182A- 068). No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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