High-energy dose of therapeutic ultrasound in the treatment of patellar tendinopathy: protocol of a randomized placebo-controlled clinical trial.

BACKGROUND: Patellar tendinopathy is an extremely debilitating condition and its treatment usually requires a combination of clinical approaches. Therapeutic ultrasound (TUS) is one of the most available electrophysical agent in rehabilitation settings; however, there is also a lack of high-quality studies that test different dosimetric aspects of TUS. Thus, the purpose of this study is to evaluate the short-, medium-, and long-term effects of the combination of high-energy TUS with a rehabilitation program for patellar tendinopathy. METHODS: This will be a randomized, placebo-controlled trial with blinding of patients, assessors, and therapist. The setting is an outpatient physical therapy clinic. We will recruit 66 participants (male and female) aged between 18 and 40 years and presenting with patellar tendinopathy. A treatment combining high-energy dose TUS and a rehabilitation program for patellar tendinopathy will be delivered twice a week for 8 weeks. The control group will receive the same treatment, but with a placebo TUS. The effectiveness of the intervention will be measured at the beginning (baseline), midpoint (4 weeks), and end of treatment (8 weeks), as well as at 3- and 6-months post-treatment. Primary outcomes will be pain intensity (visual analogue scale, VAS), and VISA-P questionnaire and primary time points will be baseline (T0) and the end of the program (T2). Also, IPAQ-short form questionnaire, muscle strength (manual dynamometry), 2D kinematics, pain pressure threshold (PPT) algometry, thermography, and magnetic resonance imaging (MRI) will be collected. DISCUSSION: TUS will be applied in an attempt to enhance the results obtained with the rehabilitation program proposed in this study, as well as stimulate some repair responses in individuals undergoing treatment for patellar tendinopathy, which in turn may optimize and improve treatment programs for patellar tendinopathy as well as to establish new guidelines for the application of TUS. TRIAL REGISTRATION: This study was prospectively registered at April-3rd-2018 and updated at September-1st-2019 in the Brazilian Registry of Clinical Trials (REBEC) under the registration number: RBR-658n6w.

Effectiveness of Shockwave Treatment Combined With Eccentric Training for Patellar Tendinopathy: A Double-Blinded Randomized Study.

OBJECTIVE: To evaluate the effectiveness of a combined treatment of focused shockwave therapy (ESWT) and eccentric training compared with sham-shockwave therapy (placebo) and eccentric training in participants with patellar tendinopathy (PT) after 24 weeks. DESIGN: Randomized controlled trial. SETTING: Sports medicine departments of a university hospital and a general hospital in the Netherlands. PARTICIPANTS: Fifty-two physically active male and female participants with a clinical diagnosis of PT (mean age: 28.6 years; range, 18-45) were randomly allocated to the ESWT (n = 22) or sham shockwave (n = 30). INTERVENTIONS: Extracorporeal shockwave therapy and sham shockwave were applied in 3 sessions at 1-week intervals with a piezoelectric device. All participants were instructed to perform eccentric exercises (3 sets of 15 repetitions twice a day) for 3 months on a decline board at home. MAIN OUTCOME MEASURES: The Victorian Institute of Sport Assessment-Patella (VISA-P) scores (primary), pain scores during functional knee loading tests, and Likert score (secondary) were registered at baseline and at 6, 12, and 24 weeks after the start with the ESWT or sham-shockwave treatment. RESULTS: No significant differences for the primary and secondary outcome measures were found between the groups. In the ESWT/eccentric group, the VISA-P increased from 54.5 ± 15.4 to 70.9 ± 17.8, whereas the VISA-P in the sham-shockwave/eccentric group increased from 58.9 ± 14.6 to 78.2 ± 15.8 (between-group change in VISA-P at 24 weeks -4.8; 95% confidence interval, -12.7 to 3.0, P = 0.150). CONCLUSIONS: This study showed no additional effect of 3 sessions ESWT in participants with PT treated with eccentric exercises. The results should be interpreted with caution because of small sample size and considerable loss to follow-up, particularly in the ESWT group.

Effects of low-intensity pulsed ultrasound on new trabecular bone during bone-tendon junction healing in a rabbit model: a synchrotron radiation micro-CT study.

This study was designed to evaluate the effects of low-intensity pulsed ultrasound on bone regeneration during the bone-tendon junction healing process and to explore the application of synchrotron radiation micro computed tomography in three dimensional visualization of the bone-tendon junction to evaluate the microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits underwent partial patellectomy to establish a bone-tendon junction injury model at the patella-patellar tendon complex. Animals were then divided into low-intensity pulsed ultrasound treatment (20 min/day, 7 times/week) and placebo control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for each group and time point). The patella-patellar tendon specimens were harvested for radiographic, histological and synchrotron radiation micro computed tomography detection. The area of the newly formed bone in the ultrasound group was significantly greater than that of control group at postoperative week 8 and 16. The high resolution three dimensional visualization images of the bone-tendon junction were acquired by synchrotron radiation micro computed tomography. Low-intensity pulsed ultrasound treatment promoted dense and irregular woven bone formation at week 8 with greater bone volume fraction, number and thickness of new trabecular bone but with lower separation. At week 16, ultrasound group specimens contained mature lamellar bone with higher bone volume fraction and thicker trabeculae than that of control group; however, there was no significant difference in separation and number of the new trabecular bone. This study confirms that low-intensity pulsed ultrasound treatment is able to promote bone formation and remodeling of new trabecular bone during the bone-tendon junction healing process in a rabbit model, and the synchrotron radiation micro computed tomography could be applied for three dimensional visualization to quantitatively evaluate the microarchitecture of new bone in bone-tendon junction.

High-dose electron beam sterilization of soft-tissue grafts maintains significantly improved biomechanical properties compared to standard gamma treatment.

Allografts have gained increasing popularity in anterior cruciate ligament (ACL) reconstruction. However, one of the major concerns regarding allografts is the possibility of disease transmission. Electron beam (Ebeam) and Gamma radiation have been proven to be successful in sterilization of medical products. In soft tissue sterilization high dosages of gamma irradiation have been shown to be detrimental to biomechanical properties of grafts. Therefore, it was the objective of this study to compare the biomechanical properties of human bone-patellar tendon-bone (BPTB) grafts after ebeam with standard gamma irradiation at medium (25 kGy) and high doses (34 kGy). We hypothesized that the biomechanical properties of Ebeam irradiated grafts would be superior to gamma irradiated grafts. Paired 10 mm-wide human BPTB grafts were harvested from 20 donors split into four groups following irradiation with either gamma or Ebeam (each n = 10): (A) Ebeam 25 kGy, (B) Gamma 25 kGy, (C) Ebeam 34 kGy (D) Gamma 34 kGy and ten non-irradiated BPTB grafts were used as controls. All grafts underwent biomechanical testing which included preconditioning (ten cycles, 0-20 N); cyclic loading (200 cycles, 20-200 N) and a load-to-failure (LTF) test. Stiffness of non-irradiated controls (199.6 ± 59.1 N/mm) and Ebeam sterilized grafts did not significantly differ (152.0 ± 37.0 N/mm; 192.8 ± 58.0 N/mm), while Gamma-irradiated grafts had significantly lower stiffness than controls at both irradiation dosages (25 kGy: 126.1 ± 45.4 N/mm; 34 kGy: 170.6 ± 58.2 N/mm) (p < 0.05). Failure loads at 25 kGy were significantly lower in the gamma group (1,009 ± 400 N), while the failure load was significantly lower in both study groups at high dose irradiation with 34 kGy (Ebeam: 1,139 ± 445 N, Gamma: 1,073 ± 617 N) compared to controls (1,741 ± 304 N) (p < 0.05). Creep was significantly larger in the gamma irradiated groups (25 kGy: 0.96 ± 1.34 mm; 34 kGy: 1.06 ± 0.58 mm) than in the Ebeam (25 kGy: 0.50 ± 0.34 mm; 34 kGy: 0.26 ± 0.24 mm) and control (0.20 ± 0.18 mm) group that did not differ significantly. Strain difference was not different between either control or study groups (controls: 1.0 ± 0.03; Ebeam 34 kGy 1.04 ± 0.018; Gamma 34 kGy 1.0 ± 0.028; 25 kGy: 1.4 ± 2,0; 34 kGy: 1.1 ± 1.1). The most important result of this study was that ebeam irradiation showed significantly less impairment of the biomechanical properties than gamma irradiation. Considering the results of this study and the improved control of irradiation application with electronic beam, this technique might be a promising alternative in soft-tissue sterilization.

Experimental remodellation of extracorporeal irradiated autogenous and allogenic patellar grafts.

BACKGROUND: Irradiated autografts have been used to aid the recovery of bone defects, and the results are well documented. Recently, bone allografts with tendinous attachments have been used to restore the function of joints. Similar reconstructions can be performed with irradiated autografts. However, little information is available on the biology of extracorporeal irradiated tendon autografts. QUESTIONS/PURPOSES: An experimental rabbit model was used to investigate the quality of healing and remodeling of the irradiated autogenous patellar tendon graft after 3 and 12 weeks using immunohistochemical and morphometric analyses. METHODS: New Zealand rabbits (n = 40) were randomly divided into autograft and allograft groups. The right knees of all animals served as the control (sham). The patellar tendon graft of the control right knee was reimplanted into its original location without any processing, while the patellar tendon of the left knee in the autograft group was reimplanted into the original location after 50 Gy irradiation. In the allograft group, the patellar tendon was sutured to the knee of another rabbit following 50 Gy irradiation. Five rabbits from each group were sacrificed and examined histologically. RESULTS: There were significant differences in the number of fibroblasts after 12 weeks between allograft and sham groups (P = 0.002). On the other hand, there were no differences between the allograft and autograft groups at the 12th week (P = 0.139). The difference in fibroblast numbers between autograft and allograft groups was statistically significant after the 3rd week (P < 0.05). Collagen fibril thickness was different between both the allograft and sham groups (P = 0.002) and the allograft and autograft groups at the 12th week (P = 0.000). Collagen fibrils were thicker in the sham and autograft groups compared with the allograft group at the 3rd week of evaluation (P < 0.05). The Ki67 index was significantly different between the allograft and sham groups at the 12th week (P < 0.032), while there was no difference between the allograft and autograft groups (P > 0.05). At the 3rd week, Ki67 reactivity was higher in the allograft group compared with the other two groups (P < 0.05).

Sterilization with electron beam irradiation influences the biomechanical properties and the early remodeling of tendon allografts for reconstruction of the anterior cruciate ligament (ACL).

Although allografts for anterior cruciate ligament (ACL) replacement have shown advantages compared to autografts, their use is limited due to the risk of disease transmission and the limitations of available sterilization methods. Gamma sterilization has shown detrimental effects on graft properties at the high doses required for sufficient pathogen inactivation. In our previous in vitro study on human patellar tendon allografts, Electron beam (Ebeam) irradiation showed less detrimental effects compared to gamma sterilization (Hoburg et al. in Am J Sports Med 38(6):1134-1140, 2010). To investigate the biological healing and restoration of the mechanical properties of a 34 kGy Ebeam treated tendon allograft twenty-four sheep underwent ACL replacement with either a 34 kGy Ebeam treated allograft or a non-sterilized fresh frozen allograft. Biomechanical testing of stiffness, ultimate failure load and AP-laxity as well as histological analysis to investigate cell, vessel and myofibroblast-density were performed after 6 and 12 weeks. Native sheep ACL and hamstring tendons (HAT, each n = 9) served as controls. The results of a previous study analyzing the remodeling of fresh frozen allografts (n = 12) and autografts (Auto, n = 18) with the same study design were also included in the analysis. Statistics were performed using Mann-Whitney U test followed by Bonferroni-Holm correction. Results showed significantly decreased biomechanical properties during the early remodeling period in Ebeam treated grafts and this was accompanied with an increased remodeling activity. There was no recovery of biomechanical function from 6 to 12 weeks in this group in contrast to the results observed in fresh frozen allografts and autografts. Therefore, high dose Ebeam irradiation investigated in this paper cannot be recommended for soft tissue allograft sterilization.

Effects of (60)Co gamma radiation dose on initial structural biomechanical properties of ovine bone--patellar tendon--bone allografts.

Gamma radiation is established as a procedure for inactivating bacteria, fungal spores and viruses. Sterilization of soft tissue allografts with high dose (60)Co gamma radiation has been shown to have adverse effects on allograft biomechanical properties. In the current study, bone-patellar tendon-bone (BPTB) allografts from 32 mature sheep were divided into two treatment groups: low-dose radiation at 15 kGy (n = 16) and high-dose radiation at 25 kGy (n = 16) with the contralateral limb serving as a 0 kGy (n = 32) non-irradiated control. Half of the tendons from all treatment groups were biomechanically tested to determine bulk BPTB mechanical properties, cancellous bone compressive properties, and interference screw pull-out strength. The remaining tissues were prepared, implanted, and mechanically tested in an acute in vitro anterior crucial ligament (ACL) reconstruction. Low-dose radiation did not adversely affect mechanical properties of the tendon allograft, bone, or ACL reconstruction compared to internal non-irradiated control. However, high-dose radiation compromised bulk tendon load at failure and ultimate strength by 26.9 and 28.9%, respectively (P < 0.05), but demonstrated no negative effect on the cancellous bone compressive properties or interference screw pull-out strength. Our findings suggest that low dose radiation (15 kGy) does not compromise the mechanical integrity of the allograft tissue, yet high dose radiation (25 kGy) significantly alters the biomechanical integrity of the soft tissue constituent.

Laser-induced modification of the patellar ligament tissue: comparative study of structural and optical changes.

The effects of non-ablative infrared (IR) laser treatment of collagenous tissue have been commonly interpreted in terms of collagen denaturation spread over the laser-heated tissue area. In this work, the existing model is refined to account for the recently reported laser-treated tissue heterogeneity and complex collagen degradation pattern using comprehensive optical imaging and calorimetry toolkits. Patella ligament (PL) provided a simple model of type I collagen tissue containing its full structural content from triple-helix molecules to gross architecture. PL ex vivo was subjected to IR laser treatments (laser spot, 1.6 mm) of equal dose, where the tissue temperature reached the collagen denaturation temperature of 60 ± 2°C at the laser spot epicenterin the first regime, and was limited to 67 ± 2°C in the second regime. The collagen network was analyzed versus distance from the epicenter. Experimental characterization of the collagenous tissue at all structural levels included cross-polarization optical coherence tomography, nonlinear optical microscopy, light microscopy/histology, and differential scanning calorimetry. Regressive rearrangement of the PL collagen network was found to spread well outside the laser spot epicenter (>2 mm) and was accompanied by multilevel hierarchical reorganization of collagen. Four zones of distinct optical and morphological properties were identified, all elliptical in shape, and elongated in the direction perpendicular to the PL long axis. Although the collagen transformation into a random-coil molecular structure was occasionally observed, it was mechanical integrity of the supramolecular structures that was primarily compromised. We found that the structural rearrangement of the collagen network related primarily to the heat-induced thermo-mechanical effects rather than molecular unfolding. The current body of evidence supports the notion that the supramolecular collagen structure suffered degradation of various degrees, which gave rise to the observed zonal character of the laser-treated lesion.

Mechanical properties of radiation-sterilised human Bone-Tendon-Bone grafts preserved by different methods.

Patellar tendon auto- and allo-grafts are commonly used in orthopedic surgery for reconstruction of the anterior cruciate ligaments (ACL). Autografts are mainly used for primary reconstruction, while allografts are useful for revision surgery. To avoid the risk of infectious disease transmission allografts should be radiation-sterilised. As radiation-sterilisation supposedly decreases the mechanical strength of tendon it is important to establish methods of allograft preservation and sterilisation assuring the best quality of grafts and their safety at the same time. Therefore, the purpose of this study was to compare the tensile strength of human patellar tendon (cut out as for ACL reconstruction), preserved by various methods (deep fresh freezing, glycerolisation, lyophilisation) and subsequently radiation-sterilised with doses of 0, 25, 50 or 100 kGy. Bone-Tendon-Bone grafts (BTB) were prepared from cadaveric human patella tendons with both patellar and tibial attachments. BTB grafts were preserved by deep freezing, glycerolisation or lyophilisation and were subsequently radiation-sterilised with doses of 0 (control), 25, 50 or 100 kGy. All samples were subjected to mechanical failure tensile tests with the use of Instron system in order to estimate their mechanical properties. All lyophilised grafts were rehydrated before performing of those tests. Obtained mechanical tests results of examined grafts suggest that deep-frozen irradiated grafts retain their initial mechanical properties to an extent which does not exclude their clinical application.

The effect of gamma irradiation on anterior cruciate ligament allograft biomechanical and biochemical properties in the caprine model at time zero and at 6 months after surgery.

BACKGROUND: High levels of gamma irradiation are required to eliminate the risk of bacterial and viral transmission during implantation of musculoskeletal allografts. The effects of high levels of gamma irradiation on anterior cruciate ligament allograft biomechanics are still not known. HYPOTHESIS: High-dose gamma irradiation (4 Mrad) adversely affects anterior cruciate ligament allograft biomechanics at surgery and at 6 months after surgery and affects biochemistry at 6 months. STUDY DESIGN: Controlled laboratory study. METHODS: Bilateral anterior cruciate ligament reconstructions were performed in 18 adult goats, with one knee receiving an irradiated patellar tendon allograft (4 Mrad) and the other receiving a frozen control allograft (0 Mrad). In 6 recipients (time zero group), graft pairs were tested immediately after sacrifice, and load relaxation of the femur-allograft-tibia preparation was measured during cyclic anterior displacement. Twelve recipients received bilateral anterior cruciate ligament reconstructions, staged 2 months apart, and were sacrificed a mean of 6 months postoperatively. Load relaxation and tensile failure testing were performed, followed by allograft biochemistry assessment. RESULTS: At time zero, irradiated grafts showed less load relaxation than did contralateral controls, but by 6 months, the trend had reversed because of decreases in control graft relaxation, with no changes in irradiated graft relaxation. By 6 months, irradiated grafts showed lower stiffness and maximum force compared to controls but no differences in modulus, maximum stress, or biochemistry. CONCLUSION: High levels of gamma irradiation affect anterior cruciate ligament allograft subfailure viscoelastic and structural properties but not material or biochemical properties over time. CLINICAL RELEVANCE: Although high levels of gamma irradiation may inactivate infectious agents, this treatment is not a feasible clinical option because of altered allograft biomechanics.

Does irradiation affect the clinical outcome of patellar tendon allograft ACL reconstruction?

The clinical implications of using irradiation to sterilize allograft bone-patellar tendon-bone (BPTB) remains unknown. The purpose of this study was to compare the clinical outcome of anterior cruciate ligament (ACL) reconstruction with irradiated allograft versus autograft BPTB. We hypothesized that patients undergoing ACL reconstruction with irradiated BPTB allograft would have no significant differences in patient-reported and objective parameters compared to those undergoing autograft BPTB reconstruction. Patients who underwent ACL reconstruction with either irradiated allograft or autograft BPTB from 1996 to 2002 were eligible for this study. One hundred and two patients (39 allograft, 63 autograft) met the study criteria and were available for follow-up. The BPTB allografts were obtained from a single tissue bank and were sterilized with 2.5 Mrad of irradiation prior to distribution. Participants completed the International Knee Documentation Committee (IKDC) subjective knee form and returned for physical and radiographic examinations, instrumented measurement of laxity, and functional testing. Patients were evaluated at an average follow-up of 4.2 years (range 1.8-8.4). Those undergoing allograft reconstruction were older (44+/-8.4 vs. 25.3+/-9.3 years, p<0.001) and had a longer median time from injury to surgery (17.1 weeks vs. 9.7 weeks, p=0.04). There was no difference in IKDC Subjective Knee Scores between groups (86.7 allograft vs. 88.0 autograft, p=0.65). The average maximum manual KT-1000 side-to-side difference was 1.3 and 2.2 mm for allograft and autograft, respectively (p=0.04); however, after adjusting for age, this difference was no longer significant. 90.6% of the allograft and 82.8% of the autograft had normal/nearly normal overall IKDC physical examination rating (p=0.37). 66.7% of the allograft and 77.8% of the autograft returned to the same or more strenuous level of sports (p=0.25). Patients undergoing ACL reconstruction with irradiated allograft BPTB had similar clinical outcomes compared to those reconstructed with autograft BPTB. These data suggest that irradiation can be used to sterilize BPTB allograft without adversely affecting clinical outcome.

Thermal damage prediction for collagenous tissues part I: a clinically relevant numerical simulation incorporating heating rate dependent denaturation.

Subablative thermotherapy is frequently used for the treatment of joint instability related diseases. In this therapy, mechanically deformed collagenous tissues are thermally shrunk and the stability of the tissue is re-established. In this research, the thermal damage fields generated by three different clinical heating modalities (monopolar and bipolar radio frequency and Ho:YAG laser) are compared numerically using finite element analysis. The heating rate dependent denaturation characteristics of collagenous tissues are incorporated into the model using experimental data from in vitro experimentation with rabbit patellar tendons. It is shown that there are significant differences among the thermal damage profiles created by these modalities, explaining the main reason for the discrepancies reported in the literature in terms of the efficacy and safety of each modality. In the complementary paper, the accuracy of the model presented here is verified by in vitro experimentation with a model collagenous tissue and by quantifying the denaturation-induced birefringence change using Optical Coherence Tomography and Magnetic Resonance Imaging.

Thermomechanical analysis of soft-tissue thermotherapy.

Soft-tissue thermotherapy based on sub-ablative heating of collagenous tissues finds wide-spread application in medicine such as tissue welding, thermokeratoplasty, skin resurfacing, elimination of discogenic pain in the spine and treatment of joint instability. In this paper, heat-induced thermomechanical response characteristics of collagenous tissues are quantified by means of in vitro experimentation with a representative model tissue (New Zealand white rabbit patellar tendon). Three distinct heat-induced thermomechanical response regimes (defined by the rate of deformation and the variation of material properties) are identified. Arrhenius damage integral representation of collagenous tissue thermal history is shown to be adequate in establishing the master response curves for quantification of thermomechanical response for modeling purposes. The trade-off between the improved kinematical stability and compromised mechanical stability of the heated collagenous tissue is shown to be the major challenge hindering the success of subablative thermotherapies.

Subject variation in caprine anterior cruciate ligament reconstruction.

We studied the subject and treatment contributions to anterior cruciate ligament (ACL) reconstruction biomechanics by reexaming the results of two bilateral reconstruction studies. Bilateral reconstruction allows a comparison between treatments exposed to the same subject related healing factors. The studies examined the effects of gamma irradiation and the effects of initial graft size and initial graft laxity. In both studies different treatments were applied to contralateral limbs. We found that the subject was the best predictor of outcome, while the surgical treatments had little influence on outcome. There was a large variation between subjects despite similar treatments, and little difference between contralateral limbs despite different surgical treatments. At 26 weeks, the graft cross sectional area and modulus were most strongly influenced (p < 0.002) by the subject. We interpret this as a subject related factor is regulating the quantity and quality of the healing tissue. Potential sources of subject related factors include the subject's pre-operative condition, the activity during the post-operative period, and an intrinsic biologic response. By better understanding the source of subject variation, more successful and consistent ACL reconstructions might be achieved.

Mechanoreceptors and length of the patellar ligament after Ho-YAG laser treatment: a long-term follow-up in rabbits.

We studied the shortening and the number of mechanoreceptors in the patellar ligament up to 18 months after Ho-YAG irradiation of the ligament's surface in 35 rabbits. The ligaments shortened an average 13% immediately after irradiation. After treatment, we divided the rabbits into a mobilized or immobilized group. At 2 weeks and 12 months after treatment both groups showed no shortening of the ligament, as compared to the intact ligament while that in the mobilized group had elongated at 12 months. Fewer Pacinian and Ruffini corpuscles were found in the irradiated ligaments than in the intact ones at 2 weeks after treatment, but we found no difference between irradiated and intact ligaments at 18 months after treatment.