TET1 Regulates Skeletal Stem-Cell Mediated Cartilage Regeneration.

OBJECTIVE: Adult skeletal stem cells (SSCs) that give rise to chondrocytes, osteocytes, and stromal cells as progeny have been shown to contribute to cartilage regeneration in osteoarthritis (OA). Understanding extrinsic and intrinsic regulators of SSC fate and function can therefore identify putative candidate factors to enhance cartilage regeneration. This study explores how the DNA hydroxymethylase Tet1 regulates SSC function in OA. METHODS: We investigated the differences in the SSC lineage tree and differentiation potential in neonatal and adult Tet1+/+ and Tet1-/- mice with and without injury and upon OA induction and progression. Using RNA sequencing, the transcriptomic differences between SSCs and bone cartilage stroma progenitor cells (BCSPs) were identified in Tet1+/+ mice and Tet1-/- mice. RESULTS: Loss of Tet1 skewed the SSC lineage tree by expanding the SSC pool and enhanced the chondrogenic potential of SSCs and BCSPs. Tet1 inhibition led to enhanced chondrogenesis in human SSCs and chondroprogenitors isolated from human cartilage. Importantly, TET1 inhibition in vivo in late stages of a mouse model of OA led to increased cartilage regeneration. Transcriptomic analyses of SSCs and BCSPs lacking Tet1 revealed pathway alterations in transforming growth factor ß signaling, melatonin degradation, and cartilage development-associated genes. Lastly, we report that use of the hormone melatonin can dampen inflammation and improve cartilage health. CONCLUSION: Although Tet1 is a broad epigenetic regulator, melatonin can mimic the inhibition ability of TET1 to enhance the chondrogenic ability of SSCs. Melatonin administration has the potential to be an attractive stem cell-based therapy for cartilage regeneration.

Assessment of a Synergistic Effect of Platelet-Rich Plasma and Stem Cell-Seeded Hydrogel for Healing of Rat Chronic Rotator Cuff Injuries.

Outcomes after repair of chronic rotator cuff injuries remain suboptimal. Type-1 collagen-rich tendon hydrogel was previously reported to improve healing in a rat chronic rotator cuff injury model. Stem cell seeding of the tendon hydrogel improved bone quality in the same model. This study aimed to examine whether there was a synergistic and dose-dependent effect of platelet-rich plasma (PRP) on tendon-bone interface healing by combining PRP with stem cell-seeded tendon hydrogel. Human cadaveric tendons were processed into a hydrogel. PRP was prepared at two different platelet concentrations: an initial concentration (initial PRP group) and a higher concentration (concentrated PRP group). Tendon hydrogel was mixed with adipose-derived stem cells and one of the platelet concentrations. Methylcellulose, as opposed to saline, was used as a negative control due to comparable viscosity. The supraspinatus tendon was detached bilaterally in 33 Sprague-Dawley rats (66 shoulders). Eight weeks later, each detached tendon was repaired, and a hydrogel mixture or control was injected at the repair site. Eight weeks after repair, shoulder samples were harvested and assigned for biomechanical testing (n = 42 shoulders) or a combination of bone morphological and histological assessment (n = 24 shoulders). Biomechanical testing showed significantly higher failure load and stiffness in the concentrated PRP group than in control. Yield load in the initial and concentrated PRP groups were significantly higher than that in the control. There were no statistically significant differences between the initial and concentrated PRP groups. The addition of the highly concentrated PRP to stem cells-seeded tendon hydrogel improved healing biomechanically after chronic rotator cuff injury in rats compared to control. However, synergistic and dose-dependent effects were not seen.

Biomechanical Forces of the Lateral Knee Joint Following Meniscectomy and Meniscus Transplantation in Pediatric Cadavers.

INTRODUCTION: Lateral meniscus transplantation successfully treats symptomatic meniscus deficiency in children. Although clinical outcomes are well-characterized, joint forces in meniscus-deficient and transplant states are unknown. The purpose of this study was to characterize contact area (CA) and contact pressures (CP) of transplanted lateral meniscus in pediatric cadavers. We hypothesize that (1) compared with the intact state, meniscectomy will decrease femorotibial CA and increase CP, and increase contact pressure (CP) and (2) compared with the meniscectomy state, meniscus transplantation will improve contact biomechanics toward the intact meniscus state. METHODS: Pressure-mapping sensors were inserted underneath the lateral meniscus of eight cadaver knees aged 8 to 12 years. CA and CP on the lateral tibial plateau were measured in the intact, meniscectomy, and transplant states each at 0°, 30°, and 60° of knee flexion. Meniscus transplant was anchored with transosseous pull-out sutures and sutured to the joint capsule with vertical mattresses. The effects of meniscus states and flexion angle on CA and CP were measured by a two-way analysis of variance repeated measures model. One-way analysis of variance measured pairwise comparisons between meniscus states. RESULTS: Regarding CA, at 0°, no differences between the groups reached significance. Meniscectomy reduced CA at 30° ( P = 0.043) and 60° ( P = 0.001). Transplant and intact states were comparable at 30°. At 60°, transplant significantly increased CA ( P = 0.04). Regarding contact pressure, the average pressure increased with meniscectomy at all angles of flexion (0° P = 0.025; 30° P = 0.021; 60° P = 0.016) and decreased with transplant relative to respective intact values. Peak pressure increased with meniscectomy at 30° ( P = 0.009) and 60° ( P = 0.041), but only reached intact comparable values at 60°. Pairwise comparisons support restoration of average CP with transplant, but not peak CP. DISCUSSION: Pediatric meniscus transplantation improves average CP and CA more than peak CP, but does not completely restore baseline biomechanics. Net improvements in contact biomechanics after transplant, relative to the meniscectomy state, support meniscus transplant. STUDY DESIGN: Descriptive laboratory study, Level III.

A Biomechanical Comparison of All-Inside Versus Transtibial Meniscus Root Repair Techniques.

BACKGROUND: Meniscus root tears are associated with chondral injury, early degenerative change, and a high conversion rate to total knee arthroplasty. It is well-established that meniscus root tears lead to decreased femorotibial contact area, increased peak contact pressures, and increased stress on the articular cartilage. PURPOSE: To evaluate the biomechanical characteristics of the all-inside meniscus root repair procedure and compare it with the previously described transtibial technique. STUDY DESIGN: Controlled laboratory study. METHODS: Nine paired cadaveric knees were prepared by removing skin, subcutaneous tissues, quadriceps muscles, patella, and patellar tendon, while leaving the capsule in place. Pressure-mapping sensors were inserted, and specimens underwent compressive loading to obtain peak pressures, mean pressures, and femorotibial contact area in the medial and lateral compartments. Tests were performed as static compression tests with the knee locked at 0° of flexion. Compression testing was performed in 3 states: meniscus intact, meniscus root cut, and after meniscus root repair with an all-inside repair technique. Additionally, testing was completed on 9 pairs of cadaveric knees to compare stiffness and maximal load to failure between the all-inside and transtibial meniscus root repair techniques. RESULTS: In the medial compartment, there were significant increases in median peak pressures and median mean pressures in the root cut state as compared with the intact state (+636 kPA [95% CI, 246 to 1026] and +190 kPA [95% CI, 49 to 330], respectively). All-inside meniscus root repair restored median peak pressures and median mean pressures to approach those of the intact meniscus (+311 kPA [95% CI, -79 to 701] and +137 kPA [95% CI, -3 to 277]). In the lateral compartment, there were also significant increases in median peak pressures and median mean pressures in the root cut state as compared with the intact state (+718 kPA [95% CI, 246 to 1191] and +203 kPA [95% CI, 51 to 355]). All-inside meniscus root repair restored median peak pressures and median mean pressures such that they were not significantly different from the intact state (+322 kPA [95% CI, -150 to 795] and +18 kPA [95% CI, -134 to 171]). There was no difference between repair techniques regarding load to failure (P = .896). Transtibial meniscus root repair had significantly more stiffness (mean ± SD, 24.8 ± 9.3 N/mm) as compared with the all-inside meniscus root repair technique (13.6 ± 3.8 N/mm, P = .015). CONCLUSION: All-inside meniscus root repair reduced median peak and mean pressures to those of the native intact meniscus with the knee in extension in the cadaveric model. When compared with a transtibial meniscus root repair technique, all-inside repair demonstrated decreased stiffness and a similar load to failure. CLINICAL RELEVANCE: All-inside meniscus root repair restored mean and peak femorotibial pressures to those of the intact meniscus. Additionally, it offers a technically easier technique for management of meniscus root tears.

The efficiency of genetically modified mesenchymal stromal cells combined with a functionally graded scaffold for bone regeneration in corticosteroid-induced osteonecrosis of the femoral head in rabbits.

Core decompression (CD) with mesenchymal stromal cells (MSCs) is an effective therapy for early-stage osteonecrosis of the femoral head (ONFH). Preconditioning of MSCs, using inflammatory mediators, is widely used in immunology and various cell therapies. We developed a three-dimensional printed functionally graded scaffold (FGS), made of ß-TCP and PCL, for cell delivery at a specific location. The present study examined the efficacy of CD treatments with genetically modified (GM) MSCs over-expressing PDGF-BB (PDGF-MSCs) or GM MSCs co-over-expressing IL-4 and PDGF-BB and preconditioned for three days of exposure to lipopolysaccharide and tumor necrosis factor-alpha (IL-4-PDGF-pMSCs) using the FGS for treating steroid-induced ONFH in rabbits. We compared CD without cell-therapy, with IL-4-PDGF-pMSCs alone, and with FGS loaded with PDGF-MSCs or IL-4-PDGF-pMSCs. For the area inside the CD, the bone volume in the CD alone was higher than in both FGS groups. The IL-4-PDGF-pMSCs alone and FGS + PDGF-MSCs reduced the occurrence of empty lacunae and improved osteoclastogenesis. There was no significant difference in angiogenesis among the four groups. The combined effect of GM MSCs or pMSCs and the FGS was not superior to the effect of each alone. To establish an important adjunctive therapy for CD for early ONFH in the future, it is necessary and essential to develop an FGS that delivers biologics appropriately and provides structural and mechanical support.

Distal Metaphyseal Ulnar Shortening Osteotomy Fixation: A Biomechanical Analysis.

PURPOSE: Ulnar shortening osteotomy can be used to treat ulnar impaction syndrome and other causes of ulnar wrist pain. Distal metaphyseal ulnar shortening osteotomy (DMUSO) is one technique that has been proposed to reduce the complications seen with a diaphyseal USO or a wafer resection. However, to our knowledge, the optimal fixation construct for DMUSO has not been studied. We sought to characterize the biomechanical stiffness and rotational stability of different DMUSO constructs. METHODS: A DMUSO was performed on 40 human cadaveric ulnas using 4 different fixation constructs (10 specimens per group): one 3.0 mm antegrade screw; two 2.2 mm antegrade screws; one 3.0 mm retrograde screw; and two 2.2 mm retrograde screws. Biaxial testing using axial load and cyclical axial torque was performed until failure, defined as 10° of rotation or 2 mm displacement. Specimens were assessed for stiffness at failure. Bone density was assessed using the second metacarpal cortical percentage. RESULTS: Bone density was similar between all 4 testing groups. Of the 4 groups, the 2 antegrade screw group exhibited the highest rotational stiffness of 232 ± 102 Nm/deg. In paired analysis, this was significantly greater than 1 retrograde screw constructs. In multivariable analysis, 2-screw constructs were significantly stiffer than 1 screw and antegrade constructs were significantly stiffer than retrograde. Maximum failure torque did not differ with orientation, but 2 screws failed at significantly higher torques. CONCLUSION: Using 2 screws for DMUSO fixation constructs may provide higher stiffness and maximum failure torque, and antegrade screw constructs may provide more stiffness than retrograde constructs. CLINICAL RELEVANCE: Antegrade screw fixation using 2 screws may provide the strongest construct for DMUSO. Antegrade fixation may be preferred because it avoids violating the distal radioulnar joint capsule and articular surface of the ulna.

Superior Capsule Reconstruction Using Acellular Dermal Allograft Secured at 45° of Glenohumeral Abduction Improves the Superior Stability of the Glenohumeral Joint in Irreparable Massive Posterosuperior Rotator Cuff Tears.

PURPOSE: The purpose of the current study was to create a dynamic cadaveric shoulder model to determine the effect of graft fixation angle on shoulder biomechanics following SCR and to assess which commonly used fixation angle (30° vs 45° of abduction) results in superior glenohumeral biomechanics. METHODS: Twelve fresh-frozen cadaveric shoulders were evaluated using a dynamic shoulder testing system. Humeral head translation, subacromial and glenohumeral contact pressures were compared among 4 conditions: 1) Intact, 2) Irreparable supra- and infraspinatus tendon tear, 3) SCR using acellular dermal allograft (ADA) fixation at 30° of abduction, and 4) SCR with ADA fixation at 45° of abduction. RESULTS: SCR at both 30° (0.287 mm, CI: -0.480 - 1.05 mm; P < .0001) and 45° (0.528 mm, CI: -0.239-1.305 mm; P = .0006) significantly decreased superior translation compared to the irreparably torn state. No significant changes in subacromial peak contact pressure were observed between any states. The average glenohumeral contact pressure increased significantly following creation of an irreparable RCT (373 kPa, CI: 304-443 vs 283 kPa, CI 214-352; P = .0147). The SCR performed at 45° (295 kPa, CI: 226-365, P = .0394) of abduction significantly decreased the average glenohumeral contact pressure compared to the RCT state. There was no statistically significant difference between the average glenohumeral contact pressure of the intact state and SCR at 30° and 45°. CONCLUSION: SCR improved the superior stability of the glenohumeral joint when the graft was secured at 30° or 45° of glenohumeral abduction. Fixation at 45° of glenohumeral abduction provided more stability than did fixation at 30°. CLINICAL RELEVANCE: Grafts attached at 45° of glenohumeral abduction biomechanically restore the glenohumeral stability after SCR using ADA better than fixation at 30° of glenohumeral abduction.

Transtibial Repair of Lateral Meniscus Posterior Root Tears Improves Contact Biomechanics in Pediatric Cadavers.

Purpose: A paucity of data exists on the treatment of pediatric lateral meniscus root tears (LMPRTs). This study aims to characterize the biomechanics of the lateral knee joint in pediatric cadavers following LMPRT and root repair. Our hypotheses were: (1) compared with the intact state, LMPRT would be associated with decreased contact area; (2) compared with the intact state, LMPRT would be associated with increased contact pressures; and (3) compared with LMPRT, root repair would restore contact area and pressures toward intact meniscus values. Methods: Eight cadaver knees (ages 8-12 years) underwent contact area and pressure testing of the lateral compartment. Tekscan pressure mapping sensors covering the tibial plateau were inserted underneath the lateral meniscus. Appropriate pressure load equivalents were applied by a robot at degrees of flexion: 0, 30, 60. Three meniscus conditions were tested: (1) intact, (2) complete root tear, and (3) repaired root tear. Root repairs were performed with transtibial pullout sutures. Statistical analysis was performed. Results: Root tear significantly decreased mean contact area at 30° (P = .0279) and 60° (P = .0397). Root repair increased mean contact area and did not significantly differ from intact states. Differences in contact pressures between meniscus states were not statistically significant. Relative to the intact state. the greatest increase in contact pressures occurred between 0° and 30°. Root repair decreased mean contact pressures at 0° and 30°. At 60°, mean contact pressures of the repair state were closer in magnitude to the tear state than the intact state. Conclusions: LMPRT decreases contact area and increases contact pressures in the lateral knee compartment. Repair of LMPRT improves tibiofemoral contact area at high (>30°) degrees of flexion and contact pressures at low (<30°) degrees of flexion. Clinical Relevance: Transosseous pullout repair is a clinically validated treatment for LMPRT. This study provides baseline biomechanics data of transtibial pullout repair of pediatric LMPRTs.

Biomechanical, Histologic, and Micro-Computed Tomography Characterization of Partial-Width Full-Thickness Supraspinatus Tendon Injury in Rats.

PURPOSE: Partial rotator cuff tears can cause shoulder pain and dysfunction and are more common than complete tears. However, few studies examine partial injuries in small animals and, therefore a robust, clinically relevant model may be lacking. This study aimed to fully characterize the established rat model of partial rotator cuff injury over time and determine if it models human partial rotator cuff tears. METHODS: We created a full-thickness, partial-width injury at the supraspinatus tendon-bone interface bilaterally in 31 Sprague-Dawley rats. Rats were euthanized immediately, and at 2-, 3-, 4-, and 8-weeks after surgery. Fourteen intact shoulders were used as controls. Samples were assessed biomechanically, histologically, and morphologically. RESULTS: Biomechanically, load to failure in controls and 8 weeks after injury was significantly greater than immediately and 3 weeks after injury. Load to failure at 8 weeks was comparable to control. However, the locations of failure were different between intact shoulders and partially injured samples. Bone mineral density at 8 weeks was significantly greater than that at 2 and 3 weeks. Although no animals demonstrated propagation to complete tear and the injury site remodeled histologically, the appearance at 8 weeks was not identical to that in the controls. CONCLUSIONS: The biomechanical properties and bone quality decreased after the injury and was restored gradually over time with full restoration by 8 weeks after injury. However, the findings were not equivalent to the intact shoulder. This study demonstrated the limitations of the current model in its application to long-term outcome studies, and the need for better models that can be used to assess chronic partial rotator cuff injuries. CLINICAL RELEVANCE: There is no small animal model that mimics human chronic partial rotator cuff tears, which limits our ability to improve care for this common condition.

Aligned Gelatin Microribbon Scaffolds with Hydroxyapatite Gradient for Engineering the Bone-Tendon Interface.

Injuries of the bone-to-tendon interface, such as rotator cuff and anterior cruciate ligament tears, are prevalent musculoskeletal injuries, yet effective methods for repair remain elusive. Tissue engineering approaches that use cells and biomaterials offer a promising potential solution for engineering the bone-tendon interface, but previous strategies require seeding multiple cell types and use of multiphasic scaffolds to achieve zonal-specific tissue phenotype. Furthermore, mimicking the aligned tissue morphology present in native bone-tendon interface in three-dimensional (3D) remains challenging. To facilitate clinical translation, engineering bone-tendon interface using a single cell source and one continuous scaffold with alignment cues would be more attractive but has not been achieved before. To address these unmet needs, in this study, we develop an aligned gelatin microribbon (µRB) hydrogel scaffold with hydroxyapatite nanoparticle (HA-np) gradient for guiding zonal-specific differentiation of human mesenchymal stem cell (hMSC) to mimic the bone-tendon interface. We demonstrate that aligned µRBs led to cell alignment in 3D, and HA gradient induced zonal-specific differentiation of mesenchymal stem cells that resemble the transition at the bone-tendon interface. Short chondrogenic priming before exposure to osteogenic factors further enhanced the mimicry of bone-cartilage-tendon transition with significantly improved tensile moduli of the resulting tissues. In summary, aligned gelatin µRBs with HA gradient coupled with optimized soluble factors may offer a promising strategy for engineering bone-tendon interface using a single cell source. Impact statement Our 3D macroporous microribbon hydrogel platform with alignment cues zonally integrated with hydroxyapatite nanoparticles enables differentiation across the bone-tendon interface within a continuous scaffold. While most interfacial scaffolds heretofore rely on composites and multilayer approaches, we present a continuous scaffold utilizing a single cell source. The synergy of niche cues with human mesenchymal stem cell (hMSC) culture leads to an over 45-fold enhancement in tensile modulus in culture. We further demonstrate that priming hMSCs towards the chondrogenic lineage can enhance the differential osteogenesis. Relying on a single cell source could enhance zone integration and scaffold integrity, along with practical benefits.

The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits.

BACKGROUND: Approximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH. METHODS: In vitro studies: Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed. RESULTS: In vitro studies: PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P < 0.001) and CMV-PDGF-BB-MSCs (P < 0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P < 0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14 days (P < 0.01), and osteogenic differentiation at 28 days (P = 0.07) than CMV-PDGF-BB-MSCs. In vivo: The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P < 0.001), greater osteoclast density (P < 0.01), and greater angiogenesis (P < 0.01) than the other treatment groups. CONCLUSION: The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.

The efficacy of lapine preconditioned or genetically modified IL4 over-expressing bone marrow-derived mesenchymal stromal cells in corticosteroid-associated osteonecrosis of the femoral head in rabbits.

Cell-based therapy for augmentation of core decompression (CD) using mesenchymal stromal cells (MSCs) is a promising treatment for early stage osteonecrosis of the femoral head (ONFH). Recently, the therapeutic potential for immunomodulation of osteogenesis using preconditioned (with pro-inflammatory cytokines) MSCs (pMSCs), or by the timely resolution of inflammation using MSCs that over-express anti-inflammatory cytokines has been described. Here, pMSCs exposed to tumor necrosis factor-alpha and lipopolysaccharide for 3 days accelerated osteogenic differentiation in vitro. Furthermore, injection of pMSCs encapsulated with injectable hydrogels into the bone tunnel facilitated angiogenesis and osteogenesis in the femoral head in vivo, using rabbit bone marrow-derived MSCs and a model of corticosteroid-associated ONFH in rabbits. In contrast, in vitro and in vivo studies demonstrated that genetically-modified MSCs that over-express IL4 (IL4-MSCs), established by using a lentiviral vector carrying the rabbit IL4 gene under the cytomegalovirus promoter, accelerated proliferation of MSCs and decreased the percentage of empty lacunae in the femoral head. Therefore, adjunctive cell-based therapy of CD using pMSCs and IL4-MSCs may hold promise to heal osteonecrotic lesions in the early stage ONFH. These interventions must be applied in a temporally sensitive fashion, without interfering with the mandatory acute inflammatory phase of bone healing.

Supplemental medial small fragment fixation adds stability to distal femur fixation: A biomechanical study.

INTRODUCTION: Bridge plating of distal femur fractures with lateral locking plates is susceptible to varus collapse, fixation failure, and nonunion. While medial and lateral dual plating has been described in clinical series, the biomechanical effects of dual plating of distal femur fractures have yet to be clearly defined. The purpose of this study was to compare dual plating to lateral locked bridge plating alone in a cadaveric distal femur gap osteotomy model. MATERIALS AND METHODS: Gap osteotomies were created in eight matched pairs of cadaveric female distal femurs (average age: 64 yrs (standard deviation ± 4.4 yrs); age range: 57-68 yrs;) to simulate comminuted extraarticular distal femur fractures (AO/OTA 33A). Eight femurs underwent fixation with lateral locked plates alone and were matched with eight femurs treated with dual plating: lateral locked plates with supplemental medial small fragment non-locking fixation. Mechanical testing was performed on an ElectroPuls E10000 materials testing system using a 10 kN/100 Nm biaxial load cell. Specimens were subject to 25,000 cycles of cyclic loading from 100-1000 N at 2 Hz. RESULTS: Two (2/8) specimens in the lateral only group failed catastrophically prior to completion of testing. All dual plated specimens survived the testing regimen. Dual plated specimens demonstrated significantly less coronal plane displacement (median 0.2 degrees, interquartile range [IQR], 0.0-0.5 degrees) compared to 2.0 degrees (IQR 1.9-3.3, p = 0.02) in the lateral plate only group. Dual plated specimens demonstrated greater bending stiffness compared to the lateral plated group (median 29.0 kN/degree, IQR 1.5-68.2 kN/degree vs median 0.50 kN/degree, IQR 0.23-2.28 kN/degree, p = 0.03). CONCLUSION: Contemporary fixation methods with a distal femur fractures are susceptible to mechanical failure and nonunion with lateral plates alone. Dual plate fixation in a cadaveric model of distal femur fractures underwent significantly less displacement under simulated weight bearing conditions and demonstrated greater stiffness than lateral plating alone. Given the significant clinical failure rates of lateral bridge plating in distal femur fractures, supplemental fixation should be considered, and dual plating of distal femurs augments mechanical stability in a clinically relevant magnitude.

Effect of porosity of a functionally-graded scaffold for the treatment of corticosteroid-associated osteonecrosis of the femoral head in rabbits.

Background/Objective: Core decompression (CD) with scaffold and cell-based therapies is a promising strategy for providing both mechanical support and regeneration of the osteonecrotic area for early stage osteonecrosis of the femoral head (ONFH). We designed a new 3D printed porous functionally-graded scaffold (FGS) with a central channel to facilitate delivery of transplanted cells in a hydrogel to the osteonecrotic area. However, the optimal porous structural design for the FGS for the engineering of bone in ONFH has not been elucidated. The aim of this study was to fabricate and evaluate two different porous structures (30% or 60% porosity) of the FGSs in corticosteroid-associated ONFH in rabbits. METHODS: Two different FGSs with 30% or 60% porosity containing a 1-mm central channel were 3D printed using polycaprolactone and ß-tricalcium phosphate. The FGS was 3-mm diameter and 32-mm length and was composed of three segments: 1-mm in length for the non-porous proximal segment, 22-mm in length for the porous (30% versus 60%) middle segment, and 9-mm in length for the 15% porous distal segment. Eighteen male New Zealand White rabbits were given a single dose of 20 â€‹mg/kg methylprednisolone acetate intramuscularly. Four weeks later, rabbits were divided into three groups: the CD group, the 30% porosity FGS group, and the 60% porosity FGS group. In the CD group, a 3-mm diameter drill hole was created into the left femoral head. In the FGS groups, a 30% or 60% porosity implant was inserted into the bone tunnel. Eight weeks postoperatively, femurs were harvested and microCT, mechanical, and histological analyses were performed. RESULTS: The actual porosity and pore size of the middle segments were 26.4% â€‹± â€‹2.3% and 699 â€‹± â€‹56 â€‹µm in the 30% porosity FGS, and 56.0% â€‹± â€‹4.5% and 999 â€‹± â€‹71 â€‹µm in the 60% porosity FGS, respectively using microCT analysis. Bone ingrowth ratio in the 30% porosity FGS group was 73.9% â€‹± â€‹15.8%, which was significantly higher than 39.5% â€‹± â€‹13.0% in the CD group on microCT (p â€‹< â€‹0.05). Bone ingrowth ratio in the 60% porosity FGS group (61.3% â€‹± â€‹30.1%) showed no significant differences compared to the other two groups. The stiffness at the bone tunnel site in the 30% porosity FGS group was 582.4 â€‹± â€‹192.3 â€‹N/mm3, which was significantly higher than 338.7 â€‹± â€‹164.6 â€‹N/mm3 in the 60% porosity FGS group during push-out testing (p â€‹< â€‹0.05). Hematoxylin and eosin staining exhibited thick and mature trabecular bone around the porous FGS in the 30% porosity FGS group, whereas thinner, more immature trabecular bone was seen around the porous FGS in the 60% porosity FGS group. CONCLUSION: These findings indicate that the 30% porosity FGS may enhance bone regeneration and have superior biomechanical properties in the bone tunnel after CD in ONFH, compared to the 60% porosity FGS. TRANSLATION POTENTIAL STATEMENT: The translational potential of this article: This FGS implant holds promise for improving outcomes of CD for early stage ONFH.

The efficacy of core decompression for steroid-associated osteonecrosis of the femoral head in rabbits.

Although core decompression (CD) is often performed in the early stage of osteonecrosis of the femoral head (ONFH), the procedure does not always prevent subsequent deterioration and the effects of CD are not fully clarified. The aim of this study is to evaluate the efficacy of CD for steroid-associated ONFH in rabbits. Twelve male and 12 female New Zealand rabbits were injected intramuscularly 20 mg/kg of methylprednisolone once and were divided into the disease control and CD groups. In the disease control group, rabbits had no treatment and were euthanized at 12 weeks postinjection. In the CD group, rabbits underwent left femoral CD at 4 weeks postinjection and were euthanized 8 weeks postoperatively. The left femurs were collected to perform morphological, biomechanical, and histological analysis. Bone mineral density and bone volume fraction in the femoral head in the CD group were significantly higher than in the disease control group. However, no difference in the mechanical strength was observed between the two groups. Histological analysis showed that alkaline phosphatase and CD31 positive cells significantly increased in the males after CD treatment. The number of empty lacunae in the surrounding trabecular bone was significantly higher in the CD group. The current study indicated that CD improved the morphological properties, but did not improve the mechanical strength in the femoral head at early-stage ONFH. These data suggest the need for additional biological, mechanical strategies, and therapeutic windows to improve the outcome of early-stage steroid-associated ONFH.

Quantitative and Qualitative Analyses of the Lateral Ligamentous Complex and Extensor Tendon Origins of the Elbow: An Anatomic Study.

BACKGROUND: The lateral collateral ligament complex of the elbow is important in preventing posterolateral rotary instability of the elbow. Understanding the quantitative anatomy of this ligamentous complex and the overlying extensor musculature can aid in the surgical treatment of problems affecting the lateral side of the elbow. PURPOSE: To perform qualitative and quantitative anatomic evaluations of the lateral elbow ligamentous complex and common extensor muscle origins with specific attention to pertinent osseous landmarks. STUDY DESIGN: Descriptive laboratory study. METHODS: A total of 10 nonpaired, fresh-frozen human cadaveric elbows (mean age, 42.2 years; all male) were utilized. Quantitative analysis was performed using a 3-dimensional coordinate measuring device to quantify the location of pertinent bony landmarks, tendons, and ligament footprints of the lateral side of the elbow. RESULTS: The extensor carpi radialis brevis was the only humeral footprint found to cross the radiocapitellar joint line, extending a mean 5.9 mm (95% CI, 4.7-7.0) distal to the joint line. With the elbow in full extension, the lateral ulnar collateral ligament (LUCL) humeral footprint was found 7.1 mm (95% CI, 4.7-9.4) anterior and 9.8 mm (95% CI, 8.4-11.2) distal to the lateral epicondyle and 8.6 mm (95% CI, 7.5-9.7) proximal to the radiocapitellar joint line, while the radial collateral ligament humeral footprint was found 6.6 mm (95% CI, 5.5-7.8) anterior and 5.6 mm (95% CI, 4.0-7.2) distal to the lateral epicondyle and 12.7 mm (95% CI, 11.4-14.0) proximal to the radiocapitellar joint line. The center of the ulnar attachment of the LUCL was found 1.4 mm (95% CI, 0.7-2.1) anterior and 2.4 mm (95% CI, 1.2-6.0) proximal to the supinator tubercle and 24.4 mm (95% CI, 22.7-26.1) distal to the radiocapitellar joint line. The center of the ulnar attachment of the annular ligament was found to be 17.3 mm proximal to the supinator tubercle. CONCLUSION: The current study provides measured distances of LUCL and radial collateral ligament attachments in reference to clinically relevant landmarks, which can potentially aid surgeons in performing more anatomic reconstruction or repair of the lateral ligamentous complex of the elbow.

A Small Amount of Retraction Force Results in Inadvertent Piriformis Muscle Damage During a Piriformis-Sparing Approach to the Hip.

BACKGROUND: Piriformis-sparing approaches to the hip allow surgeons to avoid releasing the piriformis tendon during total hip arthroplasty; however, the consequences of retracting an intact piriformis tendon during such an approach remain ill-defined. The present study aimed to determine the upper limit of force that can be applied during retraction of the piriformis tendon to expose the hip, and to quantify the resultant damage to the piriformis musculotendinous complex. METHODS: A patent-pending instrumented retractor was designed to record the applied force, duration, and angle of retraction during a piriformis-sparing posterior approach to the hip. In addition to the data collected with use of the instrumented retractor, damage to the piriformis muscle and tendon was quantified by a blinded observer. RESULTS: There was no damage to the piriformis tendon in 22 (96%) of 23 hips during piriformis retraction for visualization of the hip capsule; however, there was complete or partial damage to the piriformis muscle at the sacral origin, belly, or musculotendinous junction (i.e., outside the surgical field) noted in 21 (91%) of 23 hips. The mean peak force to failure of the piriformis muscle was exceedingly small (29.0 ± 9.4 N; range, 10.1 to 44.9 N). CONCLUSIONS: The mean peak force applied to the piriformis retractor is much less than the force required for several common daily activities, such as opening a door or crushing an empty aluminum can. Soft-tissue damage that occurs outside the surgical field during the retraction of unreleased muscles, like the piriformis muscle, is common and remains an uncontrolled surgical variable. This inadvertent soft-tissue damage is not routinely accounted for when accessing the invasiveness of a procedure. Hence, it is no longer adequate to define a minimally invasive surgical procedure simply as an approach that involves the limited release of anatomical structures. CLINICAL RELEVANCE: The use of instrumented retractors may redefine surgical invasiveness by providing data that could alter our understanding of the soft-tissue damage caused by retraction and open the possibility of robot-assisted or damage-limiting retractor systems.

The Effect of Resection Size in the Treatment of Cam-Type Femoroacetabular Impingement in the Typical Patient With Hip Arthroscopy: A Biomechanical Analysis.

BACKGROUND: Arthroscopic osteochondroplasty may improve range of motion and relieve pain in patients with symptomatic hip impingement. Femoral neck fracture is a risk of this procedure because of the weakening of the proximal femur. To our knowledge, there are no biomechanical studies in young human cadaveric bone evaluating the effect of osteochondroplasty on femoral neck strength. PURPOSE/HYPOTHESIS: The purpose was to evaluate loads to fracture in young human cadavers after resection depths of 25% and 40% at the head-neck junction. We hypothesized that both depths will maintain ultimate loads to failure above previously published loads, as well as above physiologic weightbearing loads. STUDY DESIGN: Descriptive laboratory study. METHODS: Cadaveric proximal femoral specimens (6 matched pairs, under the age of 47 years) were divided into 2 groups: 25% or 40% of the diameter at the head-neck junction was resected. The length of the resection was 2 cm and the width of the resection was determined by the length of the anterolateral quadrant at the head-neck junction in all cases. A compressive load was applied directly to the femoral head. Peak load, stiffness, and energy to fracture were compared between groups. RESULTS: The average peak load to fracture after 25% resection (7347 N) was significantly higher than after the 40% resection (5892 N) (P = .010). The average energy to fracture was also significantly higher in the 25% resection group (30.2 J vs 19.2 J; P = .007). The average stiffness was higher in the 25% group, although not statistically significant (P = .737). CONCLUSION: Resection depths of 25% and 40% at the anterolateral quadrant of the femoral head-neck junction may be safe at previously described functional loads such as standing and walking in the age range more typically seen in patients undergoing hip arthroscopy. Loads to fracture were significantly higher than previously reported using older cadaveric specimens. CLINICAL RELEVANCE: Currently, most surgeons limit weightbearing after femoral osteochondroplasty in part because of risk of femoral neck fracture. Given the higher observed loads to fracture, young patients could possibly bear weight sooner after surgery, although postoperative protocols should be individualized based on patient age, weight, bone density, amount of bone resected, concomitant procedures, and potential compliance with activity restrictions.

The Hip Suction Seal, Part II: The Effect of Rim Trimming, Chondrolabral Junction Separation, and Labral Repair/Refixation on Hip Distractive Stability.

BACKGROUND: The acetabular labrum contains free nerve endings, and an unstable labrum can result in increased femoral head movement during hip motion. This can be caused by chondrolabral junction (CLJ) separation, especially in association with pincer-type femoroacetabular impingement, and may contribute to hip pain. HYPOTHESIS: Rim resection alone has no effect on suction seal biomechanics. Further, separation of the CLJ changes hip suction seal biomechanics when compared with those of the native state, whereas repair and refixation with suture anchors restore these biomechanical parameters. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 12 fresh-frozen human cadaveric hips were used in this study. Hips were mounted in a saline bath on a dynamic tensile testing machine and were distracted at a rate of 0.5 mm/s from neutral position. A total of 3 parameters (force, displacement, and intra-articular pressure) were measured throughout testing. Before testing, hips were randomly allocated to 1 of 2 groups: 1 that included the CLJ separation (CLJ Cut group) and 1 that did not (CLJ Intact group). Hips were tested in the following states: (1) native, (2) rim trimming, (3) separated CLJ (CLJ Cut group only), and (4) labral repair/refixation. For each group a linear mixed-effects model was used to compare biomechanical parameters between states. RESULTS: Rim trimming did not affect any suction seal parameters relative to those of the native state. In the CLJ Cut group, no significant difference in distance to break the suction seal was observed for any states compared with that of the native state. In the CLJ Intact group, the distance to break the suction seal was significantly shorter in the labral refixation state (1.8 mm) than the native state (5.6 mm; P = .002). The maximum distraction force (62.1 ± 54.1 N) and the peak negative pressure (-36.6 ± 24.2 kPa) of the labral repair/refixation state were significantly lower than those of the native state in both groups (93.4 ± 41.7 N, P = .01; -60.7 ± 20.4 kPa, P = .02). CONCLUSION: Rim trimming did not change the biomechanical properties of the labral suction seal. Labral refixation resulted in a shorter distance to break the labral suction seal. This indicates that labral mobility is reduced by the labral refixation procedure, which could be beneficial in postoperative pain relief and labral healing. CLINICAL RELEVANCE: The labral refixation reduced labral mobility, which could be beneficial for both pain relief and labral healing to the acetabulum after pincer-type femoroacetabular impingement resection.

The Hip Suction Seal, Part I: The Role of Acetabular Labral Height on Hip Distractive Stability.

BACKGROUND: The acetabular labrum has been found to provide a significant contribution to the distractive stability of the hip. However, the influence of labral height on hip suction seal biomechanics is not known. HYPOTHESIS: The smaller height of acetabular labrum is associated with decreased distractive stability. STUDY DESIGN: Descriptive laboratory study. METHODS: A total of 23 fresh-frozen cadaveric hemipelvises were used in this study. Hips with acetabular dysplasia or femoroacetabular impingement-related bony morphologic features, intra-articular pathology, or no measurable suction seal were excluded. Before testing, each specimen's hip capsule was removed, a pressure sensor was placed intra-articularly, and the hip was fixed in a heated saline bath. Labral size was measured by use of a digital caliper. Maximum distraction force, distance to suction seal rupture, and peak negative pressure were recorded while the hip underwent distraction at a rate of 0.5 mm/s. Correlations between factors were analyzed using the Spearman rho, and differences between groups were detected using Mann-Whitney U test. RESULTS: Of 23 hips, 12 satisfied inclusion criteria. The maximum distraction force and peak negative pressure were significantly correlated (R = -0.83; P = .001). Labral height was largely correlated with all suction seal parameters (maximum distraction force, R = 0.69, P = .013; distance to suction seal rupture, R = 0.55, P = .063; peak negative pressure, R = -0.62, P = .031). Labral height less than 6 mm was observed in 5 hips, with a mean height of 6.48 mm (SD, 2.65 mm; range, 2.62-11.90 mm; 95% CI, 4.80-8.17 mm). Compared with the 7 hips with larger labra (>6 mm), the hips with smaller labra had significantly shorter distance to suction seal rupture (median, 2.3 vs 7.2 mm; P = .010) and significantly decreased peak negative pressure (median, -59.3 vs -66.9 kPa; P = .048). CONCLUSION: Smaller height (<6 mm) of the acetabular labrum was significantly associated with decreased distance to suction seal rupture and decreased peak negative pressure. A new strategy to increase the size of the labrum, such as labral augmentation, could be justified for patients with smaller labra in order to optimize the hip suction seal. CLINICAL RELEVANCE: The height of the acetabular labrum is correlated with hip suction seal biomechanics. Further studies are required to identify the clinical effects of labral height on hip stability.