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No permanent, reliable artificial tendon exists clinically. Our group developed the OrthoCoupler™ device as a versatile connector, fixed at one end to a muscle, and adaptable at the other end to inert implants such as prosthetic bones or to bone anchors. The objective of this study was to evaluate four configurations of the device to replace the extensor mechanism of the knee in goats. Within muscle, the four groups had: (A) needle-drawn uncoated bundles, (B) needle-drawn coated bundles, (C) barbed uncoated bundles, and (D) barbed coated bundles. The quadriceps tendon, patella, and patellar tendon were removed from the right hind limb in 24 goats. The four groups (n=6 for each) were randomly assigned to connect the quadriceps muscle to the tibia (with a bone plate). Specimens were collected from each operated leg and contralateral unoperated controls both for mechanical testing and histology at 90 days post-surgery. In strength testing, maximum forces in the operated leg (vs. unoperated control) were 1288±123 N (vs. 1387±118 N) for group A, 1323±144 N (vs. 1396±779 N) for group B, 930±125 N (vs. 1337±126 N) for group C, and 968±109 N (vs. 1528±146 N) for group D (mean ± SEM). The strengths of the OrthoCoupler™ legs in the needled device groups were equivalent to unoperated controls (p=0.6), while both barbed device groups had maximum forces significantly lower than their controls (p=0.001). We believe this technology will yield improved procedures for clinical challenges in orthopaedic oncology, revision arthroplasty, tendon transfer, and tendon injury reconstruction.
A successful artificial tendon, a fastener that interfaces with muscle proximally and provides a link directly or indirectly to the skeleton distally, would expand effective treatment in important applications: orthopaedic oncology, tendon transfer procedures, revision arthroplasty, and tendon injury reconstruction [1–5]. No prior artificial tendons succeeded [6–8]. Even when not weakened by adverse tissue reaction, the interface of living to non-living materials concentrates force into long-term unsustainable stress [9, 10].
Prosthetic bones and bone segments [11–13], commonly used in oncology, do not restore full motor function. Tendons sutured to a prosthetic femur  do not remain attached, except to a fibrous envelope of tissue around the implant, restoring less than normal walking ability. Scaffold-induced neotendons and autografts do not work either, as there is nothing living beyond the gap to which such tissues can heal. Tendon-transfer procedures involve reattaching and retraining of muscles can allow dramatic rehabilitation , but the available length of native tendons limits availability to a few patients , limits potential applications, and adversely affects long-term outcome [16, 17]. Revision arthroplasty will become more common , despite increases in the durability of artificial joints. An artificial tendon could provide a quick, easy linkage for reattachment to revision, allowing better rehabilitation. Patients sustain >32 million traumatic and repetitive motion injuries to tendons and ligaments , costing$30 billion per year in the U.S. alone . Tendon injuries can dramatically affect quality of life and are expected to increase in number and severity in our aging and active population. Many tendon tears and severe sprains may be amenable to artificial tendons securely anchored in the accompanying muscle[4, 5, 20].
The OrthoCoupler was designed to reduce tissue stress by enabling a low mass, high surface-area tissue interface. The large area is generally parallel to the force, allowing large ‘shear’ force transfer. In contrast, with conventional sutures, staples, barbed sutures, and hooks, the significant bearing surfaces are projections at a positive angle to the force direction, resulting in a compressive stress that is equal to the transmitted force divided by the size of the projections, often leading to tissue damage. OrthoCoupler’s increased area reduces stress, and the shear stress is lower than the normal stress it offsets [21, 22].
To increase interface area, bundles of 12-micron fibers each were chosen for two reasons. First, for a given volume of round fibers, the cumulative surface area is inversely proportional to the chosen fiber diameter. Second, fiber diameter determines tissue response. Whereas most implants become macro-encapsulated, no such poorly-vascularized capsule develops around implants ≤50 microns diameter[23, 24]. Our preliminary studies [21, 22, 25–30] confirmed that the implanted fibers, delivered in an unbraided, needle-drawn bundle, are individually surrounded by well-vascularized connective tissue. Implantation sites showed bonding strength greater than the muscle itself [22, 25, 28, 29, 31].
We also evaluated rapidly absorbable coatings were evaluated. Gelatin [32,33] alone in a concentrated aqueous solution, gelatin plus glycerin [34.35] in concentrations from 5 to 50%, and poloxamer 188, a water-soluble compound used for lubrication and coating of both absorbable and non-absorbable sutures, were tested. Glycerin in a 9:1 ratio to gelatin was selected. This combination was similar in appearance and handling to a braided suture.
A low-profile wire barb at the end of each fiber bundle would allow exposure of only the distal cut end of the quadriceps femoris, so that the device’s fiber bundles could simply be pushed into place and left. Tanner patented rigid and flexible barbs to hold sutures in place . Richards was later granted a patent for a barbed coupler comprising both filamentous and head portions . Bays, et al. patented an absorbable rigid barbed tack for arthroscopic tissue repair, pushed into place with a rigid slotted needle . For simplicity of fabrication, a stainless steel wire barb was made for this application.
The present 2×2 block design study introduced two design variables, a rapidly-absorbable coating and a wire barb at bundle ends to obviate knot-tying. Our objectives were to test the following hypotheses: (1) tensile strength 90 days post-surgery would be equivalent among the four groups and unoperated controls and ingrowth of connective tissue among the anchoring fibers would be seen histologically.
In 24 neutered male mature goats, (51.8 ± 7.6 kg; Thomas Morris Inc., Reisterstown, MD), the quadriceps tendon, patella, and patellar tendon were removed from the right hind limb. To reconnect the quadriceps muscle to the tibia (through a bone plate), 1 of 4 groups of devices (n=6 for each) was randomly assigned, having: (A) Needled uncoated bundles, (B) Needled coated bundles, (C) Barbed uncoated bundles, or (D) Barbed coated bundles. Specimens were collected from operated and contralateral control legs for mechanical testing (n = 24) and histology (n = 8) 90 days post-surgery. The same specimens that were used for mechanical testing were later used for histological evaluation.
The muscle-interfacing region of the OrthoCoupler™ consists of bundles of a few thousand fine polymer fibers each, in this case 12-μm polyester (polyethylene terephthalate, PET) fibers (Milliken & Co., Spartanburg SC). The device (Fig.1) is composed of 32 fiber bundles, which all together comprise 32 × 3,072 or 98,304 12-micron fibers. For groups A and B, the fiber bundles were each swaged into the heel of a straight 16 cm tapered needle (laboratory-made, using stainless steel wire and hypodermic tubing from McMaster-Carr, Aurora, OH) that is removed during surgery. Bundles were initially 20 cm long to allow for knot tying, then cut leaving the same implantation length as the barbed groups, described below. For groups C and D, the fiber bundles were each linked through a 12 mm long barb (Fig.2) (laboratory-made, using 0.48 mm stainless steel, McMaster-Carr). This barb obviated knot-tying of the free ends, thus reducing the length of required skin incision. To avoid clustering the barbs, the bundle lengths were staggered at 7, 8, 9, and 10 cm for a mean implantation length of 8.5 cm. For groups B and D. the fiber bundles were coated (Fig.2) with a solution of 90 g glycerin and 10 g gelatin type A 275 bloom (Fisher Scientific, Pittsburgh, PA) dissolved in 100 g deionized water.
At the opposite end was a looped portion (4.3 cm long) that is a high-strength composite of the fibers in a matrix of silicone rubber (Shin-Etsu 1300T, durometer 40A, Shin-Etsu Silicones, Inc., Akron OH), which prevents tissue adhesion and creates a solid structure custom-moldable to the attachment site. The device had 2 loops at this end, which simplifies fixation, reduces potential stress concentration, and reduces the height of the implant at the bone plate. A stainless steel bone plate served to illustrate this simple mechanical attachability.
The intermediate portion was a braided strap (10 cm long, 0.94 cm wide, cross-sectional area 0.43 cm2), which spans the distance between the muscle interfacing bundles and the prosthesis connecting loops. The silicone rubber impregnation described above continued through this strap to prevent tissue adhesion. The strap surface was molded to approximate the cross-section of the trochlear groove in which it slides.
Throughout these three portions, the polyester fibers were continuous. The quantity of fibers achieved a cross-sectional area (0.11 cm2) equal to ~1% of the muscle (11.3 cm2), a proportion that exceeds the strength of sutured and unoperated controls without causing fibrosis or swelling [21, 22, 25–30].
An ultrasonic bath (Quantrex, L&R Ultrasonics, Kearny, NJ) was used for one 15-minute wash cycle at 37°C in a 0.4% solution of Sodium Lauryl Sulfate (Fisher Scientific) in deionized water, followed by three 15-minute deionized water rinses and air-drying. The bundles were immersed in the absorbable coating solution, drawn through perforations in a Teflon sheet to smooth the coating, and air driedagain. The devices were sterilized with ethylene oxide (Anprolene, Andersen Sterilizers, Inc., Haw River, NC) with 12 hrs of exposure and 24 hrs outgassing.
Procedures were performed under general anesthesia (intramuscular Ketamine and Xylazine, 10mg and 0.2 mg/kg, respectively) followed by isoflurane inhalation titrated to effect. The University of Cincinnati Institutional Animal Care and Use Committee approved all procedures. The hair was clipped, and the skin prepared with iodophor solution over the right hind limb. A longitudinal incision was made over the anterior proximal tibia and extended over the patella to the distal end of the quadriceps femoris, and these structures exposed. For the needled treatment groups, the incision was extended proximally to expose the distal 8 to 10 cm of quadriceps muscle. The barbed devices allowed a shorter skin incision (~14 rather than 20 cm) because they did not exit the muscle and no knotting was done. The distance from the tibial tubercle to musculotendinous junction of the quadriceps was measured so that the length could be reproduced when the artificial tendon was implanted. The patellar tendon insertion was cut from the tibia. With traction on the freed tendon, the distal quadriceps femoris tendon was then transected at the level of the most proximal externally-visible quadriceps tendon fibers, and the bloc of patellar tendon, patella, and quadriceps tendon together with interdigitated distal muscle fibers removed. One or two (#1) Caprosyn™ sutures (Syneture, Mansfield, MA) were then placed in horizontal mattress fashion in the AP direction 10 mm from the cut edge of the quadriceps stump, and the ends clamped by hemostats and set aside. The anterior surface of the proximal tibia was stripped of periosteum and the knobbed metallic plate positioned and anchored with bone screws. The loops of the device assembly were then placed securely over the knobs of the metallic plate.
The PET bundles were then inserted. For the needled groups (A and B), a preloaded disposable clip was used to push 8 parallel needles at a time, into each of the 4 quadrants of the cut quadriceps stump. Exiting needle tips were grasped from the muscle surface and individually pulled through. After all fiber groups were placed, the muscle was held in position, based on the measure taken of the intact structure, and each fiber bundle was pulled through the muscle. Each pair of adjacent bundles was tied together; excess fibers were cut and removed (Fig. 3A). For the barbed groups (C and D), the bundles were individually placed by pushing each barb with the tip of a tapered 2.9mm diameter probe; no knots were used (Fig.3B).
The heavy absorbable Caprosyn™ sutures were also wrapped about the knobs external to the OrthoCoupler™ loop and tied taut, but not to a degree that visibly slackened the OrthoCoupler™. Subcutaneous tissue and skin were closed with absorbable sutures (0 Vicryl and 2-0 Vicryl, Ethicon, Somerville, NJ), followed by a dressing. Animals were maintained for 90 days, with pain management early postoperatively and regular walking thereafter. Nocasting or fixation was employed post-surgery.
At 90 days post surgery, specimens were harvested and kept at −80°C until thawing and testing. Taking care not to disturb the quadriceps muscle or patellar tendon, other tissues were trimmed at the proximal ends of femur and tibia. Two pins were placed through the proximal femur, and this region was potted in Bondo (3M, Atlanta, GA). For the controls, the same steps were taken for the proximal tibia. For the operated legs, the device was removed from the bone plate and gripped distally. Specimens were mounted in an MTS system (MTS Corp, Eden Prairie, MN), preconditioned for 10 cycles, and then failed in tension at a rate of 1 mm/sec while monitoring load and grip-to-grip displacement. No standard displacement exists for preconditioning cycles in soft tissue, but 5% of free length is common. Postulating a true free length was precluded by the aponeurosis running along the bone and muscle. Moreover, the gripping did not permit accurate length measurements of the entire specimen, so 5% of each femur length was chosen as a preconditioning displacement. Although strain rate can affect failure mode, we chose the 1 mm/sec failure rate to allow direct observation of disruption concurrently with the load cell output, and thus determine the failure mechanism. The force-elongation curves were plotted, with failure force defined as the maximum force achieved. The specimen was inspected and mechanical mode of failure—muscle failure with muscle-prosthetic bond intact, prosthetic pull-out, or a combination—recorded.
Specimens of both operated and contralateral unoperated control from 8 animals (2 from each group) were fixed in 10% buffered formalin, processed, and paraffin embedded. 5 μm thick sections were cut and mounted on glass slides, and stained with hematoxylin and eosin and Masson’s trichrome. Specific attention was given to the separation of prosthetic fibers by in-growing connective tissue and to prevalence and nature of inflammatory cells. Ingrowth and deposition of collagenous tissue were evaluated with the aid of trichrome stained sections.
Mechanical properties were compared using 2-wayANOVA. Bonferroni’s adjustment was made to account for multiple comparisons among groups. A paired student t-test was used to compare each group and its contralateral control. Significance at the p < 0.05 level was required.
Animals began walking within 24 hrs of surgery, regaining complete weight-bearing in the operated leg and normal gait by 3 wks. At explantation, no adhesion to the exposed mobile portion of the device)was noted (Fig.4). Ingrowth occurred within the fiber bundles.
Peak load typically coincided with fiber bundles pulling out of the quadriceps muscle in the operated legs; in the controls, the quadriceps muscle typically pulled off the femur. No differences in maximum force occurred between needled vs. barbed devices (p=0.1) or between coated vs. uncoated fiber bundles (p=0.5; Table 1). The strengths of the operated and control legs were not different for the needled devices (power 80%, p=0.6). Maximum forces for the barbed devices were significantly lower than for their controls (p=0.001).
No differences in linear stiffness were found between needled vs. barbed devices (p=0.1) or between coated vs. uncoated fiber bundles (p=0.3; Table 1). No differences between the operated and control legs occurred for the needled devices (p=0.3) or barbed devices (p=0.1). No differences in elongation at failure occurred between needled vs. barbed devices (p=0.1) or between coated vs. uncoated fiber bundles (p=0.3; Table 1). The elongations at failure of the operated and control legs were different for the needled devices (p=0.02), but not different for the barbed devices (p=0.3).
Grossly, no muscle atrophy or fat infiltration in the muscle around the device was observed. All the groups showed plentiful fibroblasts with spindle shaped nuclei surrounded by their abundantly produced collagen (blue on trichrome staining), organized between the fibers (Fig.5). Multiple small blood vessels containing red blood cells were present. The fibers were widely separated with the surrounding healing and inflammatory process extending into the interstices. No significant inflammatory reaction was seen.
Our objective was to evaluate 4 configurations of the OrthoCoupler™ to replace the extensor mechanism of the knee in goats. We demonstrated thorough tissue integration without evidence of microencapsulation or compromise of vascularity. In terms of strength and stiffness, the OrthoCoupler™ legs behaved similarly to the control legs in the needled groups, but elongated more at failure. The OrthoCoupler™ legs also behaved similarly to controls in the barbed groups, but required less force for the fiber bundles to pullout of the muscle. Since the desired ingrowth was found in all groups, there is no reason to believe it contributed any less strength to the barbed groups. Rather, we believe that the barb itself did not affect the strength, whereas the knots of the needled version provided some additional strength.
This outcome suggests that the needled version is more feasible than the barbed version for initial clinical applications. Also, while wire staples and sutures are commonly left in smooth muscle, we are unaware of studies on the long-term effect of such wire in functioning skeletal muscle. The study of potential enhancements for reduced exposure (e.g., a less simplistic barb design) may be useful.
This is the first study in which pull-out strength could be measured, since previously the coupling always exceeded muscle strength [21, 22, 25, 26]. This does not suggest weaker coupling in this model, however. Forces in the present study were 4.3 times those seen in the semitendinosus study, while the device was only 2.7 times the size, and device-to-muscle proportions of the implantation region were similar . This 60% higher maximum device stress is due to the fact that the semitendinosus itself tore remotely, without device pull-out, whereas the quadriceps usually remained intact until device pullout had begun. The fact that this muscle withstood proportionally higher loads seems to be due to stress-shielding by the femur through the large aponeurosis along the quadriceps. While equivalent strength to unoperated controls was obtained, this finding suggests even higher attachment strengths might be achievable in the quadriceps by increasing the number of fibers deployed in this muscle.
We believe the OrthoCoupler™ has clinical potential. Cords, rods, and cables work in acute trials [6, 9, 10], but the sutured tendon connections separate after a few days to a few weeks. Inducing neotendon to grow among prosthetic fibers has been done with carbon[7, 8], but unfavorable tissue reactions decreased mechanical properties over time. Augmenting repair with tissue factors  requires harvesting and preparation of autogenous or allogenic tissues, and has not matched the strength of intact controls.
In a previous study we tested a smaller OrthoCoupler™ in the goat semitendinosus tendon . The tendon was removed bilaterally in 8 goats. Left sides were reattached with the device, and right sides were reattached using the Krackow stitch with #5 braided polyester sutures. Fatigue strength of the device in vitro was several times the contractile force of the muscle. In strength testing at necropsy 60 days post-surgery, suture controls pulled out at 120 ± 68 N, whereas all devices were still holding after the muscle tore, remotely, at 298 ± 111 (mean ± SD) (p<0.0003). Muscle tear strength was reached with the fiber-muscle composite still intact.
This study has limitations. First, the study did not vary the time of evaluation after surgery. Future studies are underway to evaluate repairs at longer time points. Second, semi-quantitative and quantitative histological analyses were not performed. Third, histology was performed in specimens after failure testing. The observed fiber-muscle interface might not be a true representation as disruptive mechanical testing would have resulted in slipping of fibers through the muscles. Four, any bone anchor or prosthesis may be adapted simply to the distal loop(s)of an OrthoCoupler™, and replaced if needed without disrupting the loop(s). However, this study did not investigate further bone-interface possibilities. Five, in clinical repair or replacement of the extensor mechanism, the ability to integrate a salvaged or prosthetic patella with the OrthoCoupler™ could be advantageous, but such investigations were beyond the scope of this study. Six, the attachment strength of the device at the time of surgery might already be sufficient to sustain in vivo loads, but this was not studied. Caprosyn suture (absorbed in 56 days)was used to allow sufficient time for tissue integration and stability. Seven, during needled-version implantation, extensive exposure of the muscle was required, limiting use of the device to situations where such exposure could be achieved. Eight, in vitro mechanical testing is a limited assessment tool. Although the device’s holding strength exceeds passive muscle strength, this does not imply that the device can withstand all possible in vivo muscle forces. Nine, neither the device pre-implantation nor the excised tendon-patella-tendon structure were tested to compare viscoelastic properties, and estimates of fatigue strength (1867 N) and ultimate strength (4741 N) for the device alone were extrapolated from smaller versions , which do not have a braided strap.
In the current study, in vivo observations, mechanical testing, and histology support adequacy of the repair. The implanted fibers equaled <2% of the muscle cross section in the implanted region. Animals resumed walking with the operated leg within hours. Based on these results, the configuration selected for ongoing, extended-healing studies was needled coated bundles due to easier implantation and mechanical strength similar to the unoperated leg. Histology of fully vascularized integrated tissue encourages us to expect sustained strength in longer-term studies (now underway) and in different tissue models. We believe this technology may be of value for clinical challenges in orthopaedic oncology, an expanded application of tendon-transfer, revision arthroplasty, and tendon injury reconstruction.
We thank Sarma Singam and Stephen Myers for their assistance with device fabrication. This research was supported by a grant from NIH(NIAMS AR049941) given to Surgical Energetics LLC.