Arthroscopic Visualization Is a Reliable Method of Confirming Femoral Button Placement During Anterior Cruciate Ligament Reconstruction.

Purpose: To compare arthroscopic visualization with intraoperative fluoroscopy for confirming proper femoral button placement during ACLR. Methods: Fifty consecutive patients undergoing soft-tissue ACLR between March 2021 and February 2022 were evaluated for inclusion in this study. Both primary and revision ACLR cases using suspensory fixation were included. Surgeons rated their confidence of proper button placement from both an intra-articular perspective (through the femoral tunnel) and an extra-articular perspective (through the iliotibial band) by grading confidence with a Likert scale. Fluoroscopy was also performed for confirmation of proper button placement. Results: Fifty consecutive patients (35.1 ± 14.5 years of age) with soft-tissue ACLR were included. Mean surgeon Likert confidence scores for accurate button placement were as follows: 4.1 of 5 ± 0.9 from an intra-articular perspective, 4.6 of 5 ± 0.7 from an extra-articular perspective, and 8.7 of 10 ± 1.4 based on the sum of intra- and extra-articular perspectives. Fluoroscopic findings demonstrated that 48 of 50 cases had an appropriate flipped button on the lateral cortex of the femur. I total, 2 of 50 had soft-tissue interposition. Cases in which surgeons had high confidence from both intra- and extra-articular perspectives (≥9/10 sum score) were indicative of proper button placement 97% of the time. Conclusions: Arthroscopic visualization is a reliable method of confirming femoral button placement during ACLR and is sufficient to rule out intraoperative fluoroscopy during surgery. ACLR cases with high surgeon confidence from both intra- and extra-articular perspectives (sum score of 9 or greater out of 10) resulted in proper femoral button placement in 97% of cases as confirmed by intraoperative fluoroscopy. Level of Evidence: Level II, prospective cohort study.

Return to Sport in Middle-aged and Older Athletes After Unicompartmental Knee Arthroplasty at a Mean 10-Year Follow-up: Radiographic and Clinical Outcomes.

BACKGROUND: Return to sport is essential information when an athlete contemplates surgical intervention. Young athletes, <30 years of age, may undergo complex cartilage procedures or femoral/tibial osteotomies to successfully treat single-compartment knee osteoarthritis. Unicompartmental knee arthroplasty (UKA) may offer an attractive alternative option to middle-aged/older athletes with timely return to the same sport without a lengthy rehabilitation. PURPOSE: The purpose of this study was to determine if athletes are able to return to the same level of vigorous and moderate sports after fixed-bearing intramedullary nonrobotic UKA and the specific sports activities that these athletes continued to participate in at a minimum of 5 years. We hypothesized that UKA in the appropriately selected middle-aged/older athlete would yield high return to sport after UKA with high patient satisfaction. We also hypothesized that UKA would allow athletes to return to their sports of choice. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We identified 245 patients who underwent a UKA by a single surgeon between 2003 and 2017. Athletes were included if they participated in vigorous or moderate sports, as defined by the American College of Sports Medicine, and had minimum 5-year follow-up. The primary outcome was return to vigorous or moderate sports after UKA. Secondary outcomes included the Knee injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living score, KOOS Sport and Recreation score, Lysholm score, Patient Acceptable Symptom State (PASS) analysis, and radiographic analysis. RESULTS: An overall 169 athletes met the inclusion criteria and were evaluated for return to sports. A total of 98% (165/169) returned to vigorous or moderate sports participation. The mean ± SD time to return to sport was 5.2 ± 2.3 months in the 39- to 50-year-old cohort, 5.8 ± 3.2 months in athletes aged 51 to 64 years, and 5.2 ± 3.0 months in athletes aged ≥65 years. A total of 143 athletes had minimum 5-year clinical and radiographic follow-up (mean, 10 years; range, 5-19 years). Maintenance of vigorous and moderate sport was seen in 99% (142/143) of athletes at a mean 10 years. In athletes who participated in vigorous sports, the mean Lysholm score was 85 ± 17, and 83% reached the PASS for KOOS Sport and Recreation. Radiographic analysis revealed no evidence of implant loosening (ie, subsidence, radiolucency) or osteolysis, and limb alignment and posterior slope of the implant were within normal limits. CONCLUSION: Athletes returned to sport at a mean 5 months after UKA implantation, with 98% (165/169) participating in vigorous or moderate sports. UKA is recommended as an alternative procedure in middle-aged and older athletes with single-compartment osteoarthritis who are contemplating a return to vigorous or moderate sport.

The Effects of Tensioning of the Anterior Cruciate Ligament Graft on Healing after Soft Tissue Reconstruction.

The purpose of this study is to determine the effect of the magnitude of static mechanical tension on the anterior cruciate ligament (ACL) graft at the time of surgery on healing within the graft tunnels. Ninety male rats underwent unilateral ACL resection followed by reconstruction with a soft tissue tendon autograft. The ACL graft mechanical environment was modulated by different ACL graft pretension levels at the time of surgery (no pretension: 0N; moderate tension: 5N; over tension: 10N). External fixators were used to eliminate graft and joint motion during cage activity. Graft-tunnel healing was assessed at 3- and 6-week postoperatively, and articular joint surfaces were assessed at 9 weeks. Our results demonstrate that the ACL graft-tunnel healing was sensitive to different static graft pretension levels as demonstrated by different load-to-failure and stiffness properties among the different pretension levels. Pretensioning the graft to 5N (7-8% of the rat ACL ultimate load to failure) resulted in the best graft-tunnel healing as shown by higher graft-tunnel failure load and stiffness. Higher bone volume fraction was also seen in the 5N group relative to other pretension levels. Histological analysis of the graft-tunnel interface revealed differences in cellularity of the ACL graft between the 5N group and the other two groups. Furthermore, the highest graft pretension level (10N) resulted in loss of proteoglycan content among articular joint surfaces. In conclusion, we found that ACL graft-tunnel healing is sensitive to the magnitude of graft pretension at the time of surgery in a preclinical model of ACL reconstruction with joint immobilization. The combination of high-graft tension and immobilization is also deleterious for the articular surface. Further study is necessary to understand the interaction between the magnitude of graft tensioning and joint motion.

No Difference in Outcomes Detected Between Decellular Nerve Allograft and Cable Autograft in Rat Sciatic Nerve Defects.

BACKGROUND: Nerve injuries with a gap/defect represent a clinical challenge without a clear solution. Reconstruction with cable autografts is a common treatment technique, and repair with decellular nerve allograft is a newer option. The purpose of this study was to compare the functional outcomes of reconstruction with cable autografts with those of matched-diameter decellular nerve allografts to evaluate the relative importance of diameter as well as the autograft-versus-allograft nature of the reconstruction. METHODS: A unilateral 10-mm sciatic nerve defect was created in 81 genetically identical male Lewis rats and then repaired with a reverse autograft, 4 or 5 sural nerve cable autografts, or a matched-diameter decellular nerve allograft. In each group, at each time point (12, 16, and 20 weeks), all 9 animals underwent functional testing and 5 of the 9 underwent histologic analysis. Functional testing included bilateral measurements of the isometric tetanic force of the tibialis anterior (primary outcome), the weight of the tibialis anterior, and the gastrocnemius compound muscle action potential (CMAP) latency. Histologic evaluation included an axon count as well as measurement of the axon density, fiber diameter, myelin thickness, and G-ratio. RESULTS: The repair groups did not differ significantly in terms of isometric tetanic force, muscle weight, or CMAP latency, but these measurements did differ significantly according to the time after surgery (p < 0.05). The isometric tetanic force percent recovery (width of the 95% confidence interval) for the reverse autograft, cable autograft, and decellular nerve allograft was 57.7% (15.6%), 57.0% (23.4%), and 56.0% (19.7%), respectively, at 12 weeks; 69.1% (14.7%), 65.6% (18.5%), and 65.9% (29.1%) at 16 weeks; and 72.5% (18.2%), 73.7% (25.6%), and 71.8% (22.4%) at 20 weeks. Isometric tetanic force and muscle weight recovery were greater and CMAP latency was shorter at 20 and 16 weeks after surgery than they were at 12 weeks. The treatment type did not affect any of the histologic outcomes. CONCLUSIONS: In this animal study, we found that matched-diameter decellular nerve allograft was not significantly different from reverse autograft or cable graft reconstruction in terms of function and histologic outcomes. These findings support decellular nerve allograft as a viable treatment option for nerve reconstruction. CLINICAL RELEVANCE: This study showed that decellular nerve allograft was no different from cable or reverse autograft in terms of outcome measures in a rat sciatic nerve defect model. If these results are applicable clinically, it would obviate the need for autograft nerve harvest and its ensuing donor site morbidity.

Effect of Dynamic Changes in Anterior Cruciate Ligament In Situ Graft Force on the Biological Healing Response of the Graft-Tunnel Interface.

BACKGROUND: Anterior cruciate ligament (ACL) grafts that are placed for reconstruction are subject to complex forces. Current "anatomic" ACL reconstruction techniques may result in greater in situ graft forces. The biological effect of changing magnitudes of ACL graft force on graft-tunnel osseointegration is not well understood. PURPOSE: The research objective is to determine how mechanical force on the ACL graft during knee motion affects tendon healing in the tunnel. STUDY DESIGN: Controlled laboratory study. METHODS: Male rats (N = 120) underwent unilateral ACL reconstruction with a soft tissue flexor tendon autograft. ACL graft force was modulated by different femoral tunnel positions at the time of surgery to create different graft force patterns with knee motion. External fixators were used to eliminate graft load during cage activity. A custom knee flexion device was used to deliver graft load through controlled daily knee motion. Graft-tunnel healing was then assessed via biomechanical, micro-computed tomography, and histological analyses. RESULTS: ACL graft-tunnel healing was sensitive to dynamic changes in graft forces with postoperative knee motion. High ACL graft force with joint motion resulted in early inferior ACL graft load to failure as compared with knees that had low-force ACL grafts and joint motion and knees that were immobilized (mean ± SD: 5.50 ± 2.30 N vs 9.91 ± 3.54 N [ P = .013] and 10.90 ± 2.8 N [ P = .001], respectively). Greater femoral bone volume fraction was seen in immobilized knees and knees with low-force ACL grafts when compared with high-force ACL grafts at 3 and 6 weeks. CONCLUSION: The authors were able to demonstrate that ACL graft-tunnel incorporation is sensitive to dynamic changes in ACL graft force with joint motion. Early high forces on the ACL graft appear to impair graft-tunnel osseointegration. CLINICAL RELEVANCE: Current "anatomic" techniques of ACL reconstruction may result in greater graft excursion and force with knee motion. Our results suggest that the postoperative rehabilitation regimen may need to be modified during the early phase of healing to protect the reconstruction.

Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma.

Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs) isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia.

Use of a new model allowing controlled uniaxial loading to evaluate tendon healing in a bone tunnel.

The optimal mechanical loading regimen for the healing of a tendon graft in a bone tunnel is unknown. We developed a rat model that directly tensions a healing tendon graft, without the use of confounding joint motion. Fifty cycles of either 0, 3, or 6 N of tension were applied to groups daily for 3 or 6 weeks. At 3 weeks the low load (3 N) group had the highest failure load (p = 0.009), but by 6 weeks there were no differences in failure load among groups. At 3 weeks the high load (6 N) group had greater osteoclast activity compared to the immobilized (0 N) group (p < 0.05), and by 6 weeks there were significantly more osteoclasts in the high load group compared to the low load group (p = 0.01). Bone volume fraction was higher in the immobilized group compared to the 3 N load group at 3 weeks (p = 0.014) and 6 weeks (p = 0.007). At 6 weeks, the immobilized group had greater trabecular number compared to both loading groups (p < 0.05). In conclusion, low magnitude loading had a beneficial early effect but continued loading led to poorer new bone formation over time and no beneficial effect at 6 weeks, perhaps due to delayed maturation from cumulative loads. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:852-859, 2016.

Cadaveric investigation on radial nerve strain using different posterior surgical exposures for extraarticular distal humeral ORIF: merits of nerve decompression through a lateral paratricipital exposure.

OBJECTIVE: To determine whether the type of posterior surgical approach for distal humeral fracture open reduction and internal fixation influenced radial nerve strain during simulated operative retraction in a cadaveric model. METHODS: Three different posterior surgical exposures: triceps splitting, lateral paratricipital, and paratricipital with release of the lateral intermuscular septum were used. Radial nerve strain was measured using a microDVRT, while traction was applied with a digital force gauge at forces 0.1-0.3 kg. RESULTS: The lateral paratricipital with nerve decompression was superior to both the triceps splitting approach (P < 0.048) and paratricipital method without decompression (P < 0.036). There was no significant difference between the triceps splitting method and paratricipital exposure without intermuscular septum release. CONCLUSIONS: Radial nerve decompression through release of the lateral intermuscular septum through a lateral paratricipital exposure ideally decreases nerve strain during humeral open reduction and internal fixation in our cadaveric model.

ALDH Activity Correlates with Metastatic Potential in Primary Sarcomas of Bone.

Osteosarcoma (OS), chondrosarcoma (CSA), and Ewings sarcoma (ES) are the most common primary malignancies of bone, and are rare diseases. As with all sarcomas, the prognosis of these diseases ultimately depends on the presence of metastatic disease. Survival is therefore closely linked with the biology and metastatic potential of a particular bone tumor's cells. Here we describe a significant correlation of aldehyde dehydrogenase (ALDH) activity and the presence/absence of distant metastases in ten consecutive cases of human bone sarcomas. Additionally, cultured human CSA cells, which are historically chemo- and radio-resistant, may be sensitive to the ALDH inhibitor, disulfiram. While it is premature to draw broad conclusions from such a small series, the importance of ALDH activity and inhibition in the metastatic potential of primary bone sarcomas should be investigated further.

Effect of diet-induced vitamin D deficiency on rotator cuff healing in a rat model.

BACKGROUND: Few studies have considered hormonal influences, particularly vitamin D, on healing. HYPOTHESIS: Vitamin D deficiency would have a negative effect on the structure of the healing tendon-bone interface in a rat model and would result in decreased tendon attachment strength. STUDY DESIGN: Controlled laboratory study. METHODS: Vitamin D deficiency was induced in 28 male Sprague-Dawley rats using a specialized vitamin D-deficient diet and ultraviolet light restriction. Serum levels of vitamin D were measured after 6 weeks. These vitamin D-deficient animals (experimental group) plus 32 rats with normal vitamin D levels (controls) underwent unilateral detachment of the right supraspinatus tendon from the greater tuberosity of the humerus, followed by immediate repair using bone tunnel suture fixation. The animals were sacrificed at 2- and 4-week intervals after surgery for biomechanical analysis. A paired t test was used to compare serum vitamin D levels at day 0 and at 6 weeks. A nonparametric Mann-Whitney U test was used to compare load-to-failure and stiffness values between the experimental group and controls. Bone density and new bone formation at the tendon insertion site on the greater tuberosity were assessed with micro-computed tomography (CT). The organization of collagen tissue, new bone formation, vascularity at the tendon-bone interface, fibrocartilage at the tendon-bone interface, and collagen fiber continuity between the tendon and bone tissue were evaluated with safranin O and picrosirius red staining. RESULTS: Blood draws confirmed vitamin D deficiency at 6 weeks compared with time zero/baseline for rats in the experimental group (10.9 ng/mL vs 6.5 ng/mL, respectively; P < .001). Biomechanical testing demonstrated a significant decrease in load to failure in the experimental group compared with controls at 2 weeks (5.8 ± 2.0 N vs 10.5 ± 4.4 N, respectively; P < .006). There was no difference in stiffness at 2 weeks between the control and experimental groups. At 4 weeks, there was no significant difference in load to failure or stiffness between the control and experimental groups. Histological analysis showed less bone formation and less collagen fiber organization in the vitamin D-deficient specimens at 4 weeks as compared with controls. Micro-CT analysis showed no significant difference between groups for total mineral density and bone volume fraction of cortical, whole, or trabecular bone at 4 weeks. CONCLUSION: The biomechanical and histological data from this study suggest that low vitamin D levels may negatively affect early healing at the rotator cuff repair site. CLINICAL RELEVANCE: It is estimated that 1 billion people worldwide are vitamin D deficient. In the deficient state, acutely injured rotator cuffs may have a reduced ability for tendon healing. Further studies are needed to determine the exact mechanism by which vitamin D affects tendon healing and whether vitamin D supplementation can improve rotator cuff tendon healing and reduce the incidence of retears.

Dynamic contact mechanics on the tibial plateau of the human knee during activities of daily living.

Despite significant advances in scaffold design, manufacture, and development, it remains unclear what forces these scaffolds must withstand when implanted into the heavily loaded environment of the knee joint. The objective of this study was to fully quantify the dynamic contact mechanics across the tibial plateau of the human knee joint during gait and stair climbing. Our model consisted of a modified Stanmore knee simulator (to apply multi-directional dynamic forces), a two-camera motion capture system (to record joint kinematics), an electronic sensor (to record contact stresses on the tibial plateau), and a suite of post-processing algorithms. During gait, peak contact stresses on the medial plateau occurred in areas of cartilage-cartilage contact; while during stair climb, peak contact stresses were located in the posterior aspect of the plateau, under the meniscus. On the lateral plateau, during gait and in early stair-climb, peak contact stresses occurred under the meniscus, while in late stair-climb, peak contact stresses were experienced in the zone of cartilage-cartilage contact. At 45% of the gait cycle, and 20% and 48% of the stair-climb cycle, peak stresses were simultaneously experienced on both the medial and lateral compartment, suggesting that these phases of loading warrant particular consideration in any simulation intended to evaluate scaffold performance. Our study suggests that in order to design a scaffold capable of restoring 'normal' contact mechanics to the injured knees, the mechanics of the intended site of implantation should be taken into account in any pre-clinical testing regime.

A novel device to apply controlled flexion and extension to the rat knee following anterior cruciate ligament reconstruction.

We designed and validated a novel device for applying flexion-extension cycles to a rat knee in an in vivo model of anterior cruciate ligament reconstruction (ACL-R). Our device is intended to simulate rehabilitation motion and exercise post ACL-R to optimize physical rehabilitation treatments for the improved healing of tendon graft ligament reconstructions. The device was validated for repeatability of the knee kinematic motion by measuring the force versus angular rotation response from repeated trials using cadaver rats. The average maximum force required for rotating an ACL reconstructed rat knee through 100 degrees of flexion-extension was 0.4 N with 95% variability for all trials within ±0.1 N.

Recombinant human platelet-derived growth factor-BB augmentation of new-bone formation in a rat model of distraction osteogenesis.

BACKGROUND: Distraction osteogenesis creates a challenging bone-healing environment with protracted demand for cells of the osteoblast lineage. Platelet-derived growth factor-BB (PDGF-BB) is an osteoblast mitogen and chemotaxin that has been shown to accelerate and/or enhance bone-healing in several preclinical studies. The purpose of the present study was to determine whether recombinant human platelet-derived growth factor-BB (rhPDGF-BB) would have a similar effect on regenerate healing after distraction osteogenesis. METHODS: Unilateral 7-mm mid-diaphyseal femoral lengthening procedures were performed in eighty-three male Sprague-Dawley rats that were separated into five experimental groups. During the distraction period (Days 7 to 28), each animal received a weekly 50-microL injection of either sodium acetate buffer, bovine collagen dissolved in sodium acetate buffer, or one of three concentrations of rhPDGF-BB (100, 300, or 1000 microg/mL) into the distraction site. Animals from each group were killed on Days 35, 42, 49, 56, and 63. Healing was assessed with biweekly serial radiographs, micro-computed tomography of the explanted bones, and histologic analysis. RESULTS: rhPDGF-BB treatment significantly increased new-bone formation at the midconsolidation time points (Days 42, 49, and 56) as well as the union rate. On Day 49 regenerate bone volume was significantly greater in each of the three rhPDGF-BB-treated groups than in the controls (p < 0.05, p = 0.0002, and p < 0.05 for the 100, 300, and 1000 microg/mL rhPDGF-BB groups, respectively), whereas on Day 42 regenerate bone volume was significantly greater in the 300 and 1000 microg/mL rhPDGF-BB groups than in the controls (p = 0.0002 and p < 0.05, respectively) and on Day 56 regenerate bone volume was significantly greater in the 100 and 300 microg/mL rhPDGF-BB groups than in the controls (p < 0.05 and p < 0.0001, respectively). The overall union rate was 40.4% (nineteen of forty-seven) in the rhPDGF-BB-treated animals, compared with 4.5% (one of twenty-two) in the controls (p = 0.01). The radiographic and histologic results were consistent with new-bone formation as quantified by micro-computed tomography, although they were less definitive. CONCLUSIONS: The administration of exogenous rhPDGF-BB into the distraction site during diaphyseal distraction enhanced bone-healing in a rat model of distraction osteogenesis as evidenced by both increased regenerate new-bone formation and a higher union rate.