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BACKGROUND The variation in the anatomic relationship between the coracoid and the clavicle affects the biomechanical stability of coracoclavicular ligament reconstruction (CCLR). METHODS Three-dimensional computed tomography reconstruction of 85 patients was analyzed. Anatomic landmarks were used to derive the coracoclavicular sagittal reconstruction angle (sRA). The lateral concave angle, which indicated the shape of the distal clavicle, and the offsets between the clavicle and coracoid were also measured. To investigate the biomechanical effects of the sRA on CCLR, 7 computed tomography scans with different sRAs were 3D printed. Two reconstructions, a single trans-coracoclavicular tunnel and a looped reconstruction technique, were performed sequentially. Models were cyclically loaded at 70 N in the anterior, posterior, and superior directions. RESULTS The mean sRA was 68° ± 9.3° (range, 47°-85°). The superoinferior offset between the clavicle and the coracoid and the lateral concave angle positively correlated with the sRA (r = 0.359 and 0.837, respectively; P ≤ .001), whereas the anteroposterior offset had a negative correlation (r = -0.925; P < .001). The sRA had a negative correlation with the anterior displacement of the clavicle (rho = -0.96; P < .001) and a positive correlation with the posterior displacement for both surgical techniques (rho = 1.0; P < .001). CONCLUSION The anatomic orientation of the native coracoclavicular ligaments is highly variable in the sagittal plane. Low sagittal angles can reduce anterior stability, whereas high sagittal angles can reduce posterior stability of CCLR.

Hypothesis Musculoskeletal computer models provide valuable insights into shoulder biomechanics. The shoulder is a complex joint composed of glenohumeral, scapulothoracic, acromioclavicular, and sternoclavicular articulations, whose function is largely dependent on the many muscles spanning these joints. However, the range of patient-to-patient variability in shoulder function is largely unknown. We therefore assessed the sensitivity of glenohumeral forces to population-based model input parameters that were likely to influence shoulder function. Methods We constructed musculoskeletal models of the shoulder in the AnyBody Modeling System (AnyBody Technology, Aalborg, Denmark). We used inverse dynamics and static optimization to solve for glenohumeral joint forces during a simulated shoulder elevation. We generated 1000 AnyBody models by uniformly distributing the following input parameters: subject height, scapulohumeral rhythm, humeral head radius, and acromiohumeral interval. Results Increasing body height increased glenohumeral joint forces. Increasing the ratio of scapulothoracic to glenohumeral elevation also increased forces. Increasing humeral head radius and acromiohumeral interval decreased forces. The relative sensitivity of glenohumeral joint forces to input parameters was dependent on the angle of shoulder elevation. We developed an efficient method of generating and simulating musculoskeletal models representing a large population of shoulder arthroplasty patients. We found that scapulohumeral rhythm had a significant influence on glenohumeral joint force. Conclusions This finding underscores the importance of more accurately measuring and simulating scapulothoracic motion rather than using fixed ratios or average scapulothoracic motion. This modeling approach can be used to generate virtual populations for conducting efficient simulations and generating statistical conclusions.

To compare the biomechanical stability of 3 different coracoclavicular reconstruction techniques under rotational and vertical loading using a cadaveric model.In total, 12 cadaveric shoulders were used for testing. The native state was first tested then followed by 3 different reconstruction configurations using suture tapes and cortical buttons: coracoid loop (CL), single-bundle (SB), and double-bundle (DB). Superior displacement was measured by cycling an inferiorly directed force of 70 N to the scapula. The rotational stiffness of the scapula was determined by cycling the scapula in rotational displacement control between 15° of internal and external rotation. The rotational stiffness of the clavicle was determined by rotating the clavicle around its long axis 20° anteriorly and 30° posteriorly in rotational displacement control. All measurements were captured over 10 cycles at a rate of 200 Hz.Both the CL and SB techniques demonstrated significantly less internal scapular rotation stiffness. (intact: 19.70 ± 9.07 cNm/deg, CL: 3.70 ± 2.63 cNm/deg, SB:4.30 ± 2.66 cNm/deg, P.001) External scapular rotation stiffness was significantly decreased in all techniques (intact: 17.70 ± 4.43 cNm/deg, CL: 3.30 ± 1.37 cNm/deg, SB: 4.50 ± 1.56 cNm/deg, DB: 4.67 ± 1.99 cNm/deg, P.001). The CL and SB reconstructions were significantly less stiff with regards to posterior rotation of the clavicle (intact: 5.60 ± 1.80 cNm/deg, CL: 2.90 ± 1.10 cNm/deg, SB: 1.40 ± 0.65 cNm/deg, P.001). Anterior rotation stiffness of the clavicle was significantly lower in all of the reconstructions (intact: 6.95 ± 1.90 cNm/deg, CL: 3.08 ± 0.84 cNm/deg, SB: 3.64 ± 0.93 cNm/deg, DB: 4.48 ± 1.21 cNm/deg, P.001).None of the described techniques provided equivalent rotational stability in all planes compared with the native state. DB reconstruction presented stiffness characteristics closest to the native state under cyclic loading during internal scapular and posterior clavicular rotation.Additional procedures such as tendon grafting or acromioclavicular ligament reconstruction may be required to control rotational stability.

Objective Mesenchymal stem cells (MSCs) are a promising cell-based therapy treatment option for several orthopedic indications. Because culture expansion of MSC is time and cost intensive, a bedside concentration of bone marrow (BM) aspirate is used as an alternative. Many commercial systems are available but the available literature and knowledge regarding these systems is limited. We compared different point-of-care devices that concentrate BM (BMC) by focusing on technical features and quality parameters to help surgeons make informed decisions while selecting the appropriate device. Methods We compared published data on the BMC devices of Arteriocyte, Arthrex, Celling Biosciences, EmCyte, Exactech, ISTO Tech, Harvest Tech/Terumo BCT, and Zimmer/BIOMET regarding technical features (centrifugation speed/time, input/output volume, kit components, type of aspiration syringes, filter usage) and quality parameters of their final BMC product (hematocrit, concentration of platelets and total nucleated cells, concentration of MSC and connective tissue progenitor cells). Results The systems differ significantly in their technical features and centrifugation parameters. Only the fully automated systems use universal kits, which allow processing different volumes of BM. Only the Arthrex system allows selection of final hematocrit. There was no standardized reporting method to describe biologic potency. Conclusions Based on the data obtained in this review, recommending a single device is not possible because the reported data could not be compared between devices. A standardized reporting method is needed for valid comparisons. Furthermore, clinical outcomes are required to establish the true efficacy of these systems. We are conducting additional studies for more careful comparison among the devices.

Purpose Some reports have noted favorable long-term clinical results with milder postoperative arthritic changes after total meniscectomy in symptomatic patients with torn discoid lateral meniscus (DLM). This meta-analysis was conducted to compare the clinical and radiographic results between partial and total meniscectomy in patients with symptomatic DLM. Methods Studies were included in the meta-analysis if (1) they analysed patients who underwent arthroscopic surgeries for DLMs, (2) they directly compared clinical outcomes in patients treated with partial and total meniscectomies, (3) they analysed at least one parameter related to postoperative outcomes, including the Ikeuchi scale, and/or radiographic results including the Tapper and Hoover classification. Results Eight studies were finally included. The proportion of the knees with excellent or good grade appeared to be higher in partial than in total meniscectomy group, but this difference did not reach statistical significance [128/158 (81.0%) vs. 87/131 (66.4%); OR 1.62; p = 0.10; I2 = 0%]. The pooled results of the proportion of normal cartilage status or mild chondral wear (grade 0 or 1 of the Tapper and Hoover classification) were significantly much higher with partial than with total meniscectomy [228/261 (87.4%) vs. 94/169 (55.6%); OR 9.08; p Conclusion This meta-analysis showed that the radiographic outcomes of DLM were better with partial meniscectomy with or without repair than with total meniscectomy, but their clinical outcomes were similar. The findings thus suggest that meniscal preservation would be a better option than total meniscectomy for symptomatic DLM. Level of evidence II, Systematic review and Meta-analysis.

Purpose To determine the relationship between lamellar layer thickness on ultrashort echo time (UTE) magnetic resonance (MR) images and indentation stiffness of human menisci and to compare quantitative MR imaging values between two groups with normal and abnormally thick lamellar layers. Materials and Methods This was a HIPAA-compliant, institutional review board-approved study. Nine meniscal pieces were obtained from seven donors without gross meniscal pathologic results (mean age, 57.4 years ± 14.5 [standard deviation]). UTE MR imaging and T2, UTE T2*, and UTE T1ρ mapping were performed. The presence of abnormal lamellar layer thickening was determined and thicknesses were measured. Indentation testing was performed. Correlation between the thickness and indentation stiffness was assessed, and mean quantitative MR imaging values were compared between the groups. Results Thirteen normal lamellar layers had mean thickness of 232 μm ± 85 and indentation peak force of 1.37 g ± 0.87. Four abnormally thick lamellar layers showed mean thickness of 353.14 μm ± 98.36 and peak force 0.72 g ± 0.31. In most cases, normal thicknesses showed highly positive correlation with the indentation peak force (r = 0.493-0.912; P < .001 to .05). However, the thickness in two abnormal lamellar layers showed highly negative correlation (r = -0.90, P < .001; and r = -0.23, P = .042) and no significant correlation in the others. T2, UTE T2*, and UTE T1ρ values in abnormally thick lamellar layers were increased compared with values in normal lamellar layers, although only the UTE T2* value showed significant difference (P = .010). Conclusion Variation of lamellar layer thickness in normal human menisci was evident on two-dimensional UTE images. In normal lamellar layers, thickness is highly and positively correlated with surface indentation stiffness. UTE T2* values may be used to differentiate between normal and abnormally thickened lamellar layers. (©) RSNA, 2016.

Hypothesis Glenoid retroversion can be corrected with standard glenoid implants after anterior-side asymmetric reaming or by using posterior augmented glenoid implants with built-in corrections. The purpose of this study was to compare 2 augmented glenoid designs with a standard glenoid design, measure the amount of bone removed, and compute the stresses generated in the cement and bone. Methods Finite element models of 3 arthritic scapulae with varying severities of posterior glenoid wear were each implanted with 4 different implant configurations: standard glenoid implant in neutral alignment with asymmetric reaming, standard glenoid implant in retroversion, glenoid implant augmented with a posterior wedge in neutral alignment, and glenoid implant augmented with a posterior step in neutral alignment. The volume of cortical and cancellous bone removed and the percentage of implant back surface supported by cortical bone were measured. Stresses and strains in the implant, cement, and glenoid bone were computed. Results Asymmetric reaming for the standard implant in neutral version required the most bone removal, resulted in the lowest percentage of back surface supported by cortical bone, and generated strain levels that risked damage to the most bone volume. The wedged implant removed less bone, had a significantly greater percentage of the back surface supported by cortical bone, and generated strain levels that risked damage to significantly less bone volume. Conclusions The wedged glenoid implants appear to have various advantages over the standard implant for the correction of retroversion. Level of evidence Basic Science Study; Computer Modeling

The self-healing capacity of an injured meniscus is limited to the vascularized regions and is especially challenging in the inner avascular regions. As such, we investigated the use of human meniscus cell-seeded electrospun (ES) collagen type I scaffolds to produce meniscal tissue and explored whether these cell-seeded scaffolds can be implanted to repair defects created in meniscal avascular tissue explants. Human meniscal cells (derived from vascular and avascular meniscal tissue) were seeded on ES scaffolds and cultured. Constructs were evaluated for cell viability, gene expression, and mechanical properties. To determine potential for repair of meniscal defects, human meniscus avascular cells were seeded and cultured on aligned ES collagen scaffolds for 4 weeks before implantation. Surgical defects resembling "longitudinal tears" were created in the avascular zone of bovine meniscus and implanted with cell-seeded collagen scaffolds and cultured for 3 weeks. Tissue regeneration and integration were evaluated by histology, immunohistochemistry, mechanical testing, and magentic resonance imaging. Ex vivo implantation with cell-seeded collagen scaffolds resulted in neotissue that was significantly better integrated with the native tissue than acellular collagen scaffolds or untreated defects. Human meniscal cell-seeded ES collagen scaffolds may therefore be useful in facilitating meniscal repair of avascular meniscus tears.

Background Nearly 14% to 39% TKA patients report dissatisfaction causing incomplete return of function. We proposed that the kinematics of knees implanted with patient-specific prostheses using patient-specific cutting guides would be closer to normal. Methods Eighteen matched cadaver lower limbs were randomly assigned to two groups: group A was implanted with patient-specific implants using patient-specific cutting guides; group B, the contralateral knee, was implanted with a standard design using intramedullary alignment cutting guides. Knee kinematics were measured on a dynamic closed-kinetic-chain Oxford knee rig, simulating a deep knee bend and in a passive rig testing varus–valgus laxity. Results The difference from normal kinematics was lower for group A compared to group B for active femoral rollback, active tibiofemoral adduction, and for passive varus–valgus laxity. Conclusions Our results support the hypothesis that knees with patient-specific implants generate kinematics more closely resembling normal knee kinematics than standard knee designs. Clinical Relevance Restoring normal kinematics may improve function and patient satisfaction after total knee arthroplasty.

Bone water exists in different states with the majority bound to the organic matrix and to mineral, and a smaller fraction in 'free' form in the pores of cortical bone. In this study, we aimed to develop and evaluate ultrashort-TE (UTE) MRI techniques for the assessment of T2*, T1 and concentration of collagen-bound and pore water in cortical bone using a 3-T clinical whole-body scanner. UTE MRI, together with an isotope study using tritiated and distilled water (THO-H2O) exchange, as well as gravimetric analysis, were performed on ten sectioned bovine bone samples. In addition, 32 human cortical bone samples were prepared for comparison between the pore water concentration measured with UTE MRI and the cortical porosity derived from micro-computed tomography (μCT). A short T2* of 0.27 ± 0.03 ms and T1 of 116 ± 6 ms were observed for collagen-bound water in bovine bone. A longer T2* of 1.84 ± 0.52 ms and T1 of 527 ± 28 ms were observed for pore water in bovine bone. UTE MRI measurements showed a pore water concentration of 4.7-5.3% by volume and collagen-bound water concentration of 15.7-17.9% in bovine bone. THO-H2O exchange studies showed a pore water concentration of 5.9 ± 0.6% and collagen-bound water concentration of 18.1 ± 2.1% in bovine bone. Gravimetric analysis showed a pore water concentration of 6.3 ± 0.8% and collagen-bound water concentration of 19.2 ± 3.6% in bovine bone. A mineral water concentration of 9.5 ± 0.6% was derived in bovine bone with the THO-H2O exchange study. UTE-measured pore water concentration is highly correlated (R(2) = 0.72, p

Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors.

Objective Mouse models are commonly used in research applications due to the relatively low cost, highly characterized strains, as well as the availability of many genetically modified phenotypes. In this study, we characterized an ex vivo murine osteochondral repair model using human infrapatellar fat pad (IPFP) progenitor cells. Design Femurs from euthanized mice were removed and clamped in a custom multidirectional vise to create cylindrical osteochondral defects 0.5 mm in diameter and 0.5 mm deep in both condyles. The IPFP contains progenitors that are a promising cell source for the repair of osteochondral defects. For proof of concept, human IPFP-derived progenitor cells, from osteoarthritic (OA) patients, cultured as pellets, were implanted into the defects and cultured in serum-free medium with TGFβ3 for 3 weeks and then processed for histology and immunostaining. Results The custom multidirectional vise enabled reproducible creation of osteochondral defects in murine femoral condyles. Implantation of IPFP-derived progenitor cells led to development of cartilaginous tissue with Safranin O staining and deposition of collagen type II in the extracellular matrix. Conclusions We showed feasibility in creating ex vivo osteochondral defects and demonstrated the regenerative potential of OA human IPFP-derived progenitors in mouse femurs. The murine model can be used to study the effects of aging and OA on tissue regeneration and to explore molecular mechanisms of cartilage repair using genetically modified mice.

Entheses are regions where tendons and ligaments attach to bone, and are the primary target in seronegative and other diseases of the musculoskeletal (MSK) system. MRI has been widely used for visualizing features of inflammatory and degenerative MSK disease; however, normal tendons and entheses have short transverse relaxation times (T2 ), and show little or no signal with conventional clinical MRI pulse sequences, making it difficult to investigate their MR properties. In this study we examined the normal MR morphology of the cadaveric Achilles tendon and enthesis at 3 T using novel three-dimensional ultrashort echo time (3D UTE) Cones sequences, and at 11.7 T using conventional MRI sequences. We also studied the MR properties of the Achilles tendon and enthesis including T2 *, T1 , and magnetization transfer ratio (MTR). In addition, MT modeling of macromolecular proton fractions was investigated using 3D UTE Cones sequences at 3 T. Indentation testing was performed to investigate the mechanical properties of the tendons and entheses, and this was followed by histological examination. In total five specimens (

Background:Anterior cruciate ligament (ACL) reconstruction is the current standard of care for ACL tears. However, the results are not consistently successful; autografts or allografts have certain disadvantages; and synthetic grafts have had poor clinical results.Purpose:To determine if recellularization of decellularized tendons combined with mechanical stimulation in a bioreactor could replicate the mechanical properties of the native ACL and be successfully used for ACL reconstruction in vivo.Study Design:Controlled laboratory study.Methods:Porcine tibialis tendons were decellularized and then recellularized with human adult bone marrow–derived stem cells. Tendons were cultured in a tissue bioreactor that provided biaxial cyclic loading for up to 7 days. To reproduce mechanical stresses similar to those experienced by the ACL within the knee joint, the tendons were subjected to simultaneous tension and torsion in the bioreactor. Expression of tendon-specific genes and newly synthesized collagen and glycosaminoglycan were used to quantify the efficacy of recellularization and dynamic bioreactor culture. The ultimate tensile load to failure and stiffness of recellularized constructs were measured after dynamic stimulation. Finally, the tissue-engineered tendons were used to reconstruct the ACL in 24 pigs, and ultimate tensile load to failure and stiffness were assessed after 3 months.Results:Dynamic bioreactor culture significantly increased the expression of tendon-specific genes, the quantity of newly synthesized collagen and glycosaminoglycan, and the ultimate tensile load and stiffness of recellularized tendons. After in vivo reconstruction, the ultimate tensile load and stiffness of the tissue-engineered tendons increased significantly up to 3 months after surgery and were within 80% of the ultimate tensile load of the natural ACL.Conclusion:This translational study indicates that recellularization and dynamic mechanical stimuli can significantly enhance matrix synthesis and ultimate tensile load of decellularized porcine tibialis tendons. This approach to tissue engineering can be very useful for ACL reconstruction and may overcome some of the disadvantages of autografts and allografts.Clinical Relevance:Dynamic bioreactor cultivation of tissue-engineered tendons may overcome the limitations of autografts and allografts.

Background Although a loss of rotator cuff integrity leads to the superior migration of the humeral head, the parameters that characterize the anterolateral migration of the humeral head have not been established. The purpose of this study was to investigate the correlation between the translation of the humeral head scale (T-scale) and clinical outcomes of rotator cuff repair, as well as the correlation between the T-scale and radiologic parameters. Methods One hundred thirty-five consecutive patients with full-thickness rotator cuff tears underwent primary rotator cuff repair. The T-scale, which indicates the distance from the center of the humeral head to the lateral coracoacromial arch, was measured on axial computed tomography scans, and the acromiohumeral interval (AHI) was measured radiographically. The correlation of the two parameters with the clinical scores of the Japanese Orthopaedic Association and University of California–Los Angeles scores and active forward elevation (FE) were evaluated at the preoperative and postoperative stages, respectively. Results The postoperative T-scale and AHI correlated well with the postoperative FE and clinical scores in the patients with large-massive tears but not in those patients with small-medium tears and preoperative large-massive tears. A significant correlation was observed between the postoperative T-scale and AHI. The T-scale was subject to cuff repair integrity. Conclusions We demonstrated that the postoperative T-scale was well correlated with the clinical results and postoperative AHI after rotator cuff repair for large-massive tears, indicating that poor outcomes are associated with combined superior and anterolateral migration of the humeral head following retears.

Background Knee instability is emerging as a major complication after total knee arthroplasty (TKA), with ligament laxity and component alignment listed as important contributory factors. Knee balancing remains an art and is largely dependent on the surgeon's subjective “feel.” The objectives were to measure the accuracy of an electronic balancing device to document the magnitude of correction in knee balance after soft-tissue releases and measure change in knee laxity after medial release. Methods The accuracy of a second-generation electronic ligament-balancing device was compared with that of 2 mechanical balancing instruments. TKA was performed in 12 cadaver knees. Soft-tissue balance was measured sequentially before TKA, after mounting a trial femoral component, after medial release, and after resecting the posterior cruciate ligament. Coronal laxity of the knee under a 10 Nm valgus moment was measured before and after medial release. Results The electronic balancing instrument was more accurate than mechanical instruments in measuring distracted gap and distraction force. On average, before TKA, the flexion gap was wider than the extension gap, and the medial gap was tighter than the lateral gap. Medial release increased the medial gap in flexion and increased passive knee valgus laxity. Posterior cruciate ligament release increased the tibiofemoral gap in both flexion and extension with a greater increase in the lateral gap. Conclusion The second-generation electronic balancing device was significantly more accurate than mechanical instruments and could record knee balance over the entire range of flexion. More accurate soft-tissue balance may enhance outcomes after TKA.

Total shoulder arthroplasty is recommended treatment for severe osteoarthritis of the glenohumeral joint, which often results in excessive posterior wear. Two recent glenoid components with posterior augments have been designed to correct excessive posterior wear and retroversion. Our primary hypothesis was that posterior augmented glenoid designs require less bone removal than a standard glenoid design.Ten arthritic scapulae classified as Walch B2 glenoids were virtually implanted with standard, stepped, and wedged components. The volume of surgical bone removal, the maximum reaming depth, and the portion of the implant surface in contact with cancellous vs. cortical bone were calculated for each implant.The neoglenoid made up an average of 65% ± 12% of the glenoid width. Mean surgical bone volume removed was least for the wedged (2857 ± 1618 mm(3)) compared with the stepped (4307 ± 1485 mm(3); P.001) and standard (5385 ± 2348 mm(3); P.001) designs. Maximum bone depth removed for the wedged (4.2 ± 2.0 mm) was less than for the stepped (7.6 ± 1.2 mm; P.001) and standard (9.9 ± 3.2 mm; P.001). The mean percentage of the implant's back surface supported by cancellous bone was 18.2% for the standard, 8.8% for the stepped (P = .02), and 4.3% for the wedged (P = .01).Both augmented components corrected glenoid version to neutral and required less bone removal, required less reaming depth, and were supported by more cortical bone than in the standard implant. The least amount of bone removed was with the wedged design.

Magnetization transfer (MT) imaging is one way to indirectly assess pools of protons with fast transverse relaxation. However, conventional MT imaging sequences are not applicable to short T2 tissues such as cortical bone. Ultrashort echo time (UTE) sequences with TE values as low as 8 µs can detect signals from different water components in cortical bone. In this study we aim to evaluate two-dimensional UTE-MT imaging of cortical bone and its application in assessing cortical bone porosity as measured by micro-computed tomography (μCT) and biomechanical properties. In total, 38 human cadaveric distal femur and proximal tibia bones were sectioned to produce 122 rectangular pieces of cortical bone for quantitative UTE-MT MR imaging, μCT, and biomechanical testing. Off-resonance saturation ratios (OSRs) with a series of MT pulse frequency offsets (Δf) were calculated and compared with porosity assessed with μCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation and linear regression. A moderately strong negative correlation was observed between OSR and μCT porosity (R(2) = 0.46-0.51), while a moderate positive correlation was observed between OSR and yield stress (R(2) = 0.25-0.30) and failure stress (R(2) = 0.31-0.35), and a weak positive correlation (R(2) = 0.09-0.12) between OSR and Young's modulus at all off-resonance saturation frequencies. OSR determined with the UTE-MT sequence provides quantitative information on cortical bone and is sensitive to μCT porosity and biomechanical function.

Meniscus injury and degeneration have been linked to the development of secondary osteoarthritis (OA). Therapies that successfully repair or replace the meniscus are, therefore, likely to prevent or delay OA progression. We investigated the novel approach of building layers of aligned polylactic acid (PLA) electrospun (ES) scaffolds with human meniscus cells embedded in extracellular matrix (ECM) hydrogel to lead to formation of neotissues that resemble meniscus-like tissue. PLA ES scaffolds with randomly oriented or aligned fibers were seeded with human meniscus cells derived from vascular or avascular regions. Cell viability, cell morphology, and gene expression profiles were monitored via confocal microscopy, scanning electron microscopy (SEM), and real-time polymerase chain reaction (PCR), respectively. Seeded scaffolds were used to produce multilayered constructs and were examined via histology and immunohistochemistry. Morphology and mechanical properties of PLA scaffolds (with and without cells) were influenced by fiber direction of the scaffolds. Both PLA scaffolds supported meniscus tissue formation with increased COL1A1, SOX9, and COMP, yet no difference in gene expression was found between random and aligned PLA scaffolds. Overall, ES materials, which possess mechanical strength of meniscus and can support neotissue formation, show potential for use in cell-based meniscus regeneration strategies.

Large heads have been recommended to reduce the risk of dislocation after total hip arthroplasty. One of the issues with larger heads is the risk of increased wear and damage in thin polyethylene liners. Dual-mobility liners have been proposed as an alternative to large heads. We tested the wear performance of highly crosslinked dual-mobility liners under adverse conditions simulating microseparation and third-body wear. No measurable increase in polyethylene wear rate was found in the presence of third-body particles. Microseparation induced a small increase in wear rate (2.9mm(3)/million cycles). A finite element model simulating microseparation in dual-mobility liners was validated using these experimental results. The results of our study indicate that highly crosslinked dual-mobility liners have high tolerance for third-body particles and microseparation.

Background Medialization of the glenohumeral center of rotation alters the moment arm of the deltoid, can affect muscle function, and increases the risk for scapular notching due to impingement. The objective of this study was to determine the effect of position of the glenosphere on deltoid efficiency and the range of glenohumeral adduction. Methods Scapulohumeral bone models were reconstructed from computed tomography scans and virtually implanted with primary or reverse total shoulder arthroplasty implants. The placement of the glenosphere was varied to simulate differing degrees of “medialization” and inferior placement relative to the glenoid. Muscle and joint forces were computed during shoulder abduction in OpenSim musculoskeletal modeling software. Results The average glenohumeral joint reaction forces for the primary total shoulder arthroplasty were within 5% of those previously reported in vivo. Superior placement or full lateralization of the glenosphere increased glenohumeral joint reaction forces by 10% and 18%, respectively, relative to the recommended reverse total shoulder arthroplasty position. The moment arm of the deltoid muscle was the highest at the recommended baseline surgical position. The baseline glenosphere position resulted in a glenohumeral adduction deficit averaging more than 10° that increased to more than 25° when the glenosphere was placed superiorly. Only with full lateralization was glenohumeral adduction unaffected by superoinferior placement. Discussion/Conclusion Selecting optimum placement of the glenosphere involves tradeoffs in bending moment at the implant-bone interface, risk for impingement, and deltoid efficiency. A viable option is partially medializing the glenosphere, which retains most of the benefits of deltoid efficiency and reduces the risk for scapular notching.

Hip dislocation is a major short-term complication after total hip arthroplasty (THA). One factor thought to reduce the risk for dislocation is head size. We constructed subject-specific computer models to study the effect of head size on risk for postoperative dislocation. Femoral and acetabular geometry was constructed after segmenting CT scans of nine hips. CAD models of THA components with four head diameters (28, 32, 36, and 44 mm) were virtually implanted. Hip capsular ligaments were simulated using rigid-body ellipsoids connected by non-linear springs. Posterior dislocation was simulated during a rise from a low chair; anterior dislocation was simulated during a pivot activity. Intraoperative stability tests were simulated for anterior or posterior dislocation. While rising from a low chair (posterior dislocation) and during the pivot activity (anterior dislocation), increasing head size significantly increased hip flexion angle at dislocation and generated higher dislocation moments. Larger heads reduced the risk for dislocation. Intraoperative stability tests detected the relative increased resistance to dislocation despite differences in the absolute magnitude of moments. This model can be useful preclinical tool for assessing design changes, the effect of component placement, and the activity-based risk for dislocation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1525–1531, 2014.

Background The goat is one of the most commonly used preclinical models for focal defect repair and regeneration. While the biomechanics of the human knee has been studied extensively, less is known about the biomechanics of the caprine knee. Differences between human and caprine knees have not been quantified and their significance is largely unknown. Methods We conducted a biomechanical analysis of the differences in goat and human knees to assess the validity of these preclinical in vivo models. Results CT and MRI scans revealed several differences in articular geometry: the caprine tibial plateaux were more convex and the menisci were significantly thicker and covered a larger proportion of the tibial articular surface. Caprine cartilage thickness was consistently thinner, while elastic modulus on indentation testing was consistently stiffer than human cartilage measured at eight different articular locations. Contact area and pressure were measured with electronic pressure sensors under loads normalized by multiples of body weight and at knee flexion angles reported for walking. The highest peaks in contact pressure were measured in the patellofemoral joint in goat and human knees. Peak contact pressure measured at 2 times body weight at the goat tibiofemoral joint at 70° flexion was significantly higher than for any other condition at the human tibiofemoral joint. Conclusion These differences in contact conditions might explain the lower quality of local repair reported for caprine femoral condylar defects relative to trochlear defects. Further comparative analysis, including biologic response, is necessary to determine the extent to which the goat knee reproduces clinical conditions.

Meniscus contains heterogeneous populations of cells that have not been fully characterized. Cell phenotype is often lost during culture; however, culture expansion is typically required for tissue engineering. We examined and compared cell-surface molecule expression levels on human meniscus cells from the vascular and avascular regions and articular chondrocytes while documenting changes during culture-induced dedifferentiation.Expressions of 16 different surface molecules were examined by flow cytometry after monolayer culture for 24 h, 1 week, and 2 weeks. Menisci were also immunostained to document the spatial distributions of selected surface molecules.Meniscus cells and chondrocytes exhibited several similarities in surface molecule profiles with dynamic changes during culture. A greater percentage of meniscal cells were positive for CD14, CD26, CD49c, and CD49f compared to articular chondrocytes. Initially, more meniscal cells from the vascular region were positive for CD90 compared to cells from the avascular region or chondrocytes. Cells from the vascular region also expressed higher levels of CD166 and CD271 compared to cells from the avascular region. CD90, CD166, and CD271-positive cells were predominately perivascular in location. However, CD166-positive cells were also located in the superficial layer and in the adjacent synovial and adipose tissue.These surface marker profiles provide a target phenotype for differentiation of progenitors in tissue engineering. The spatial location of progenitor cells in meniscus is consistent with higher regenerative capacity of the vascular region, while the surface progenitor subpopulations have potential to be utilized in tears created in the avascular region.

Purpose Some reports have noted favorable long-term clinical results with milder postoperative arthritic changes after total meniscectomy in symptomatic patients with torn discoid lateral meniscus (DLM). This meta-analysis was conducted to compare the clinical and radiographic results between partial and total meniscectomy in patients with symptomatic DLM. Methods Studies were included in the meta-analysis if (1) they analyzed patients who underwent arthroscopic surgeries for DLMs, (2) they directly compared clinical outcomes in patients treated with partial and total meniscectomies, (3) they analyzed at least one parameter related to postoperative outcomes, including the Ikeuchi scale, and/or radiographic results including the Tapper and Hoover classification. Results Eight studies were finally included. The proportion of the knees with excellent or good grade appeared to be higher in partial than in total meniscectomy group, but this difference did not reach statistical significance (128/158 [81.0 %] vs. 87/131 [66.4 %]; OR 1.62; p = 0.10; I2 = 0 %). The pooled results of the proportion of normal cartilage status or mild chondral wear (grade 0 or 1 of the Tapper and Hoover classification) was significantly much higher with partial than with total meniscectomy (228/261 [87.4 %] vs. 94/169 [55.6 %]; OR 9.08; p Conclusion This meta-analysis showed that the radiographic outcomes of DLM were better with partial meniscectomy with or without repair than with total meniscectomy, but their clinical outcomes were similar. The findings thus suggest that meniscal preservation would be a better option than total meniscectomy for symptomatic DLM. Level of Evidence II, Systematic review and meta-analysis.

To identify novel genes and pathways specific to the superficial zone (SZ), middle zone (MZ), and deep zone (DZ) of normal articular cartilage.Articular cartilage was obtained from the knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. The zone-specific DNA array data obtained from human tissue were compared to array data obtained from bovine cartilage. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions.The greatest differences in genome-wide RNA expression data were between the SZ and DZ in both human and bovine cartilage. The MZ, being a transitional zone between the SZ and DZ, thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biologic processes that were enriched in the SZ relative to the DZ included, most prominently, extracellular matrix-receptor interactions, cell adhesion molecule functions, regulation of actin cytoskeleton, ribosome-related functions, and signaling aspects such as the IFN, IL4, Cdc42/Rac, and JAK/STAT signaling pathways. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR/SMRTE.These differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations.

Customized patient instrumentation (CPI) combines preoperative planning with customized cutting jigs to position and align implants during total knee arthroplasty (TKA). We compared postoperative implant alignment of patients undergoing surgery with CPI to traditional TKA instrumentation for accuracy of implant placement. Twenty-five consecutive TKAs using CPI were analyzed. Preoperative CT scans of the lower extremities were segmented using a computer program. Limb alignment and mechanical axis were computed. Virtual implantation of computer-aided design models was done. Postoperative coronal and sagittal view radiographs were obtained. Using 3D image-matching software, relative positions of femoral and tibial implants were determined. Twenty-five TKAs implanted using traditional instrumentation were also analyzed. For CPI, difference in alignment from the preoperative plan was calculated. In the CPI group, the mean absolute difference between the planned and actual femoral placements was 0.67° in the coronal plane and 1.2° in the sagittal plane. For tibial alignment, the mean absolute difference was 0.9° in the coronal plane and 1.3° in the sagittal plane. For traditional instrumentation, difference from ideal placement for the femur was 1.5° in the coronal plane and 2.3° in the sagittal plane. For the tibia, the difference was 1.8° in the coronal plane. CPI achieved accurate implant positioning and was superior to traditional TKA instrumentation.

Mechanical loading is believed to be a critical factor in the development and treatment of knee osteoarthritis. However, the contact forces to which the knee articular surfaces are subjected during daily activities cannot be measured clinically. Thus, the ability to predict internal knee contact forces accurately using external measures (i.e., external knee loads and muscle electromyographic [EMG] signals) would be clinically valuable. We quantified how well external knee load and EMG measures predict internal knee contact forces during gait. A single subject with a force-measuring tibial prosthesis and post-operative valgus alignment performed four gait patterns (normal, medial thrust, walking pole, and trunk sway) to induce a wide range of external and internal knee joint loads. Linear regression analyses were performed to assess how much of the variability in internal contact forces was accounted for by variability in the external measures. Though the different gait patterns successfully induced significant changes in the external and internal quantities, changes in external measures were generally weak indicators of changes in total, medial, and lateral contact force. Our results suggest that when total contact force may be changing, caution should be exercised when inferring changes in knee contact forces based on observed changes in external knee load and EMG measures. Advances in musculoskeletal modeling methods may be needed for accurate estimation of in vivo knee contact forces.

Lower body positive pressure (LBPP) treadmills permit significant unweighting of patients and have the potential to enhance recovery following lower limb surgery. We determined the efficacy of an LBPP treadmill in reducing knee forces in vivo. Subjects, implanted with custom electronic tibial prostheses to measure forces in the knee, were tested on a treadmill housed within a LBPP chamber. Tibiofemoral forces were monitored at treadmill speeds from 1.5 mph (0.67 m/s) to 4.5 mph (2.01 m/s), treadmill incline from � 108 to þ108, and four treadmill chamber pressure settings adjusted to decrease net treadmill reaction force from 100% to 25% of the subject's body weight (BW). The peak axial tibiofemoral force ranged from 5.1 times BW at a treadmill speed of 4.5 mph (2.01 m/s) and a pressure setting of 100% BW to 0.8 times BW at 1.5 mph (0.67 m/s) and a pressure setting of 25% BW. Peak knee forces were significantly correlated with walking speed and treadmill reaction force (R 2 ¼ 0.77, p ¼ 0.04). The LBPP treadmill might be an effective tool in the rehabilitation of patients following lower-extremity surgery. The strong correlation between tibiofemoral force and walking speed and treadmill reaction forces allows for more precisely achieving the target knee forces desired during early rehabilitation. 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

The objective was to determine the safety, feasibility, and effects of anti-gravity gait training on functional outcomes (Knee Injury and Osteoarthritis Outcome Score [KOOS], the Timed Up and Go test [TUG], Numerical Rating Scale [NRS] for pain) with the AlterG® Anti-Gravity Treadmill® device for total knee arthroplasty (TKA) rehabilitation. Subjects (N = 30) were randomized to land-based vs anti-gravity gait training over 4 weeks of physical therapy after TKA. Adverse events, complications, and therapist satisfaction were recorded. All patients completed rehabilitation protocols without adverse events. KOOS, TUG, and NRS scores improved in both groups with no significant differences between groups. For the AlterG group, Sports/Recreation and Quality of Life subscales of the KOOS had the most improvement. At the end of physical therapy, TUG and NRS pain scores improved from 14 seconds to 8 seconds and from 2.8 to 1.1, respectively. Subjectively, therapists reported 100% satisfaction with the AlterG. This initial pilot study demonstrated that the AlterG Anti-Gravity Treadmill device was safe and feasible. While functional outcomes improved over time with use of the anti-gravity gait training, further studies are needed to define the role of this device as an alternative or adjunct to established rehabilitation protocols.

BackgroundOne potential mechanism for early superficial cartilage wear in normal joints is alteration of the lubricant content and quality of synovial fluid. The purpose of this study was to determine if the concentration and quality of the lubricant, hyaluronan, in synovial fluid: (1) was similar in left and right knees; (2) exhibited similar age-associated trends, whether collected postmortem or antemortem; and (3) varied with age and grade of joint degeneration.MethodsHuman synovial fluid of donors (23-91 years) without osteoarthritis was analyzed for the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, 0.5-1 MDa, and 0.03-0.5 MDa. Similarity of data between left and right knees was assessed by reduced major axis regression, paired t-test, and Bland-Altman analysis. The effect of antemortem versus postmortem collection on biochemical properties was assessed for age-matched samples by unpaired t-test. The relationships between age, joint grade, and each biochemical component were assessed by regression analysis.ResultsJoint grade and the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, and 0.5-1 MDa in human synovial fluid showed good agreement between left and right knees and were similar between age-matched patient and cadaver knee joints. There was an age-associated decrease in overall joint grade (-15%/decade) and concentrations of hyaluronan (-10.5%/decade), and hyaluronan in the molecular weight ranges of 2.5-7 MDa (-9.4%/decade), 1-2.5 MDa (-11.3%/decade), 0.5-1 MDa (-12.5%/decade), and 0.03-0.5 MDa (-13.0%/decade). Hyaluronan concentration and quality was more strongly associated with age than with joint grade.ConclusionsThe age-related increase in cartilage wear in non-osteoarthritic joints may be related to the altered hyaluronan content and quality of synovial fluid.

Retinal ganglion cells (RGCs) are responsible for the transfer of signals from the retina to the brain. As part of the central nervous system, RGCs are unable to regenerate following injury, and implanted cells have limited capacity to orient and integrate in vivo. During development, secreted guidance molecules along with signals from extracellular matrix and the vasculature guide cell positioning, for example, around the fovea, and axon outgrowth; however, these changes are temporally regulated and are not the same in the adult. Here, we combine electrospun cell transplantation scaffolds capable of RGC neurite guidance with thermal inkjet 3D cell printing techniques capable of precise positioning of RGCs on the scaffold surface. Optimal printing parameters are developed for viability, electrophysiological function and, neurite pathfinding. Different media, commonly used to promote RGC survival and growth, were tested under varying conditions. When printed in growth media containing both brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), RGCs maintained survival and normal electrophysiological function, and displayed radial axon outgrowth when printed onto electrospun scaffolds. These results demonstrate that 3D printing technology may be combined with complex electrospun surfaces in the design of future retinal models or therapies.

Introduction Malalignment can result in poor clinical outcomes and increased wear. However, component malalignment can occur even when overall limb mechanical axis is within the normal anatomic range. We studied the effect of component malalignment in the presence of acceptable knee alignment in knee arthroplasty. Methods Sixteen tibial inserts retrieved at revision surgery were laser-mapped to measure wear. Average implantation duration was 7.7 years (range, 1 to 13). Early (postprimary) and final (prerevision) radiographs were analyzed for overall alignment (limb, femoral and tibial components) and osteolysis. Results The tibial components were initially aligned in a mean of 1.3 ± 1.7° varus (range, –1.5 to 4.5°), which increased to 3.2 ± 2.9° (range, –2.0 to 8.0°) at the time of revision (p = 0.05). Tibial components initially placed in greater than 3° varus were associated with almost twice the volumetric penetration rate. Anatomic knee angles were 5.4 ± 0.9° valgus (range, 4.0 to 7.0°) in the post-primary radiographs and decreased in prerevision radiographs to 3.8 ± 2.6° (range, –1.0 to 7.5°), (p = 0.04). Discussion Tibial varus was associated with increased medial compartment wear and total wear, thus affecting osteolysis in addition to local destruction of the bearing surface. Varus malalignment as low as 3° may result in accelerated wear, even if overall limb alignment is nearly ideal. These results indicate that tibial component alignment is an important factor associated with tibial tray subsidence and polyethylene wear even when limb alignment is neutral.

Background Press-fit humeral components for total shoulder arthroplasty have notable potential complications that may be minimized by preoperative templating and improvements in stem design. The purpose of this study was to develop a 3-dimensional templating technique for the humeral stem and to validate this templating in cadaveric specimens. Materials and methods A cylindrical stem and a stem with a rectangular cross-section were selected for templating and force measurements. Templating was carried out for 15 clinical patients and 16 cadaveric shoulders, including calculation of the cortical-implant volume ratio (CIVR). Insertion forces for stem broaching and impaction were measured for 15 patients and 8 paired cadaveric shoulders. Hoop strain and periprosthetic fractures were monitored in cadaveric shoulders with strain gauges. Results A significant difference in the CIVR was noted between rectangular and cylindrical stems. No difference was observed in impact forces for ideally sized rectangular or cylindrical stems. A difference in insertion forces was found between oversized cylindrical and oversized rectangular implant stems and also between ideal and oversized cylindrical implant stems. The difference in maximal hoop strain between ideally sized rectangular and cylindrical stems was also statistically significant. Conclusions CIVR is useful to predict an ideal humeral stem size. Cylindrical stems have a different design rationale for fixation than rectangular stems. Surgeon awareness of the fixation rationale for a particular stem design is important because different stem types have different effects on the insertion force. More anatomic humeral stem designs may help to minimize the risk of complications and optimize stem fixation.

We describe the use of ultrashort echo time (UTE) sequences and fast spin echo sequences to assess cortical bone using a clinical 3T scanner. Regular two- and three-dimensional UTE sequences were used to image both bound and free water in cortical bone. Adiabatic inversion recovery prepared UTE sequences were used to image water bound to the organic matrix. Two-dimensional fast spin echo sequences were used to image free water. Regular UTE sequences were used together with bicomponent analysis to measure T*2s and relative fractions of bound and free water components in cortical bone. Inversion recovery prepared UTE sequences were used to measure the T*2 of bound water. Saturation recovery UTE sequences were used to measure the T1 of bone water. Eight cadaveric human cortical bone samples and a lower leg specimen were studied. Preliminary results show two distinct components in UTE detected signal decay, a single component in inversion recovery prepared UTE detected signal decay, and a single component in saturation recovery UTE detected signal recovery. Regular UTE sequences appear to depict both bound and free water in cortical bone. Inversion recovery prepared UTE sequences appear to depict water bound to the organic matrix. Two-dimensional fast spin echo sequences appear to depict bone structure corresponding to free water in large pores.

Dynamic loading and perfusion culture environments alone are known to enhance cartilage extracellular matrix (ECM) production in dedifferentiated articular chondrocytes. In this study, we explored whether a combination of these factors would enhance these processes over a free-swelling (FS) condition using adult human articular chondrocytes embedded in 2% alginate. The alginate constructs were placed into a bioreactor for perfusion (P) only (100 μL/per minute) or perfusion and dynamic compressive loading (PL) culture (20% for 1 h, at 0.5 Hz), each day. Control FS alginate gels were maintained in six-well static culture. Gene expression analysis was conducted on days 7 and 14, while cell viability, immunostaining, and mechanical property testing were performed on day 14 only. Total glycosaminoglycan (GAG) content and GAG synthesis were assessed after 14 days. Col2a1 mRNA expression levels were significantly higher (at least threefold; p0.05) in both bioreactor conditions compared with FS by days 7 and 14. For all gene studies, no significant differences were seen between P and PL treatments. Aggrecan mRNA levels were not significantly altered in any condition although both GAG/DNA and (35)S GAG incorporation studies indicated higher GAG retention and synthesis in the FS treatment. Collagen type II protein deposition was low in all samples, link protein distribution was more diffuse in FS condition, and aggrecan deposition was located in the outer regions of the alginate constructs in both bioreactor conditions, yet more uniformly in the FS condition. Catabolic gene expression (matrix metalloproteinase 3 [MMP3] and inducible nitric oxide synthase [iNOS]) was higher in bioreactor conditions compared with FS, although iNOS expression levels decreased to approximately fourfold less than the FS condition by day 14. Our data indicate that conditions created in the bioreactor enhanced both anabolic and catabolic responses, similar to other loading studies. Perfusion was sufficient alone to promote this dual response. PL increased the deposition of aggrecan surrounding cells compared with the other conditions; however, overall low GAG retention in the bioreactor system was likely due to both perfusion and catabolic conditions created. Optimal conditions, which permit appropriate anabolic and catabolic processes for accumulation of ECM and tissue remodeling for neocartilage development, specifically for humans, are needed.

Objectives To determine the histological patterns of posterior cruciate ligament (PCL) degeneration during aging and in relation to changes in articular cartilage and anterior cruciate ligament (ACL) across the entire adult age spectrum. Methods Human knee joints (n=120 from 65 donors) were processed within 72 h of postmortem. Articular cartilage surfaces were graded macroscopically. Each PCL was histologically evaluated for inflammation, mucinous changes, chondroid metaplasia, cystic changes and orientation of collagen fibres. The severity of PCL degeneration was classified as normal, mild, moderate or severe. PCL scores were compared to ACL and cartilage scores from the same knees. Results All knees had intact PCL. Histologically, 6% were normal, 76% showed mild, 12% moderate and 9% severe degeneration. Fibre disorientation was the most prevalent and severe change. Histological grades of PCL and ACL correlated, but significantly fewer PCL than ACL showed severe changes. There was a weaker correlation between aging and total histological PCL scores (R=0.26) compared to aging and ACL scores (R=0.42). ACL scores correlated with cartilage scores (R=0.54) while PCL scores increased with the severity of osteoarthritis from grades 0 to III but not between osteoarthritis grades III–IV (R=0.32). In knees with ruptured ACL, the PCL scores correlated with cartilage scores of the lateral compartment. Conclusions PCL histopathological changes were less severe than in the ACL. PCL degeneration was associated with ACL and cartilage damage. The lack of correlation with age indicates independent pathways for PCL versus ACL degeneration.

Quantifying muscle and joint forces over a broad range of weight bearing loads during exercise may provide data required to improve prosthetic materials and better protect against muscle and bone loss. Collectively, leg intramuscular pressure (IMP), ground reaction force (GRF), and the instrumented tibial tray force measurements provide a comprehensive assessment of leg muscle and joint biomechanical effects of gravity during exercise. Titration of body weight (BW) by lower body negative pressure (LBNP) and lower body positive pressure (LBPP) can reproducibly modulate IMP within leg muscle compartments. In addition, previous studies document peak tibial forces during various daily activities of 2.2 to 2.5 BW. The study objective was to determine the IMPs of the leg, axial compressive force on the tibia in vivo, vertical GRF, and knee range of motion during altered BW levels using LBPP and LBNP treadmill exercise. We hypothesize that peak GRF, peak tibial forces, and peak IMPs of the leg correlate linearly with percent BW, as generated across a broad range of upright LBPP and supine LBNP exercise. When running at 2.24 m/s the leg IMPs significantly increased over the loading range of 60% to 140% BW with LBPP and LBNP ( P < 0.001); as expected, leg IMPs were significantly higher when running compared with standing ( P < 0.001). During upright LBPP, total axial force at the knee increased linearly as a function of BW at 0.67 m/s ( R2 = 0.90) and 1.34 m/s ( R2 = 0.98). During supine LBNP, total axial force at the knee increased linearly as a function of BW at 0.67 m/s ( R2 = 0.98) and 1.34 m/s ( R2 = 0.91). The present study is the first to measure IMPs and peak tibial forces in vivo during upright LBPP, upright LBNP, and supine LBNP exercise. These data will aid the development of rehabilitation exercise hardware and prescriptions for patients and astronauts.

Current cartilage tissue engineering strategies cannot as yet fabricate new tissue that is indistinguishable from native cartilage with respect to zonal organization, extracellular matrix composition, and mechanical properties. Integration of implants with surrounding native tissues is crucial for long-term stability and enhanced functionality. In this study, we developed a bioprinting system with simultaneous photopolymerization capable for three-dimensional (3D) cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with human chondrocytes were printed to repair defects in osteochondral plugs (3D biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was 395.73±80.40 kPa, which was close to the range of the properties of native human articular cartilage. Printed human chondrocytes maintained the initially deposited positions due to simultaneous photopolymerization of surrounded biomaterial scaffold, which is ideal in precise cell distribution for anatomic cartilage engineering. Viability of printed human chondrocytes increased 26% in simultaneous polymerization than polymerized after printing. Printed cartilage implant attached firmly with surrounding tissue and greater proteoglycan deposition was observed at the interface of implant and native cartilage in Safranin-O staining. This is consistent with the enhanced interface failure strength during the culture assessed by push-out testing. Printed cartilage in 3D biopaper had elevated glycosaminoglycan (GAG) content comparing to that without biopaper when normalized to DNA. These observations were consistent with gene expression results. This study indicates the importance of direct cartilage repair and promising anatomic cartilage engineering using 3D bioprinting technology.

For decades, implantable sensors have been used in research to provide comprehensive understanding of the biomechanics of the human musculoskeletal system. These complex sensor systems have improved our understanding of the in vivo environment by yielding in vivo measurements of force, torque, pressure, and temperature. Historically, implants have been modified to be used as vehicles for sensors and telemetry systems. Recently, microfabrication and nanofabrication technology have sufficiently evolved that wireless, passive sensor systems can be incorporated into implants or tissue with minimal or no modification to the host implant. At the same time, sensor technology costs per unit have become less expensive, providing opportunities for use in daily clinical practice. Although diagnostic implantable sensors can be used clinically without significant increases in expense or surgical time, to date, orthopaedic smart implants have been used exclusively as research tools. These implantable sensors can facilitate personalized medicine by providing exquisitely accurate in vivo data unique to each patient.

With the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the desired 2D and 3D locations, bioprinting has great potential to develop promising approaches in translational medicine and organ replacement. The most recent advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review. Bioprinting has no or little side effect to the printed mammalian cells and it can conveniently combine with gene transfection or drug delivery to the ejected living systems during the precise placement for tissue construction. With layer-by-layer assembly, 3D tissues with complex structures can be printed using scanned CT or MRI images. Vascular or nerve systems can be enabled simultaneously during the organ construction with digital control. Therefore, bioprinting is the only solution to solve this critical issue in thick and complex tissues fabrication with vascular system. Collectively, bioprinting based on thermal inkjet has great potential and broad applications in tissue engineering and regenerative medicine. This review article introduces some important patents related to bioprinting of living systems and the applications of bioprinting in tissue engineering field.

Objective Mechanical injury induces cell death in cartilage and triggers a remodeling process that ultimately can manifest as osteoarthritis (OA). Autophagy is a process for turnover of intracellular organelles and macromolecules that protects cells during stress responses. This study determined changes and functions of autophagy following mechanical injury to cartilage.

Objective The development and patterns of spontaneous age-related changes in the anterior cruciate ligament (ACL) and their relationship to articular cartilage degeneration are not well characterized. This study was undertaken to investigate the types and temporal sequence of age-related ACL changes and to determine their correlation with cartilage lesion patterns at all stages of osteoarthritis (OA) development in human knee joints without prior joint trauma. Methods Human knee joints (n = 120 from 65 donors ages 23–92) were obtained at autopsy, and ACLs and cartilage were graded macroscopically and histologically. Inflammation surrounding the ACL was assessed separately. Results Histologic ACL substance scores and ligament sheath inflammation scores increased with age. Collagen fiber disorganization was the earliest and most prevalent change. The severity of mucoid degeneration and chondroid metaplasia in the ACL increased with the development of cartilage lesions. A correlation between ACL degeneration and cartilage degeneration was observed, especially in the medial compartment of the knee joint. Conclusion Our findings indicate that ACL degeneration is highly prevalent in knees with cartilage defects and may even precede cartilage changes. Hence, ACL deficiencies may not only be important in posttraumatic OA, but may also be a feature associated with knee OA pathogenesis in general.

The Success of Hydroxyapatite-Coated Acetabular Components Has Not Been Consistent. Plasma-Sprayed Hydroxyapatite Coatings Work Well on Nonporous Substrates but Do Not Coat the Inner Surfaces of Open-Porous Substrates. Solution Deposition Can Generate Consistent Bioceramic Coats on Porous Surfaces that More Closely Mimic the Trabecular Pattern and Biochemistry at the Bone Interface. we Compared Bone Response to the Following Implants: Porous-Coated Ti6al4v Cylinders with 1 of 3 Treatments: Plasma Sprayed with Hydroxyapatite (HA), Coated with a Solution-Deposited Biomimetic Apatite Coating (BA), and Untreated (Control). Bilateral Femurs in 36 Rabbits Were Implanted with One of the above Implants. Bone Ingrowth for HA and BA Surfaces Was Significantly Higher than that for Control Surfaces. No Fragmentation or Debris Production Was Evident in the Apatite Coat of the BA Group. A Biomimetic Coat of Solution-Deposited Apatite May Be Resistant to Coating Delamination and Particle Generation.

Force production in skeletal muscle is proportional to the amount of overlap between the thin and thick filaments, which, in turn, depends on their lengths. Both thin- and thick-filament lengths are precisely regulated and uniform within a myofibril. While thick-filament lengths are essentially constant across muscles and species (∼1.65 μm), thin-filament lengths are highly variable both across species and across muscles of a single species. Here, we used a high-resolution immunofluorescence and image analysis technique (distributed deconvolution) to directly test the hypothesis that thin-filament lengths vary across human muscles. Using deltoid and pectoralis major muscle biopsies, we identified thin-filament lengths that ranged from 1.19 ± 0.08 to 1.37 ± 0.04 μm, based on tropomodulin localization with respect to the Z-line. Tropomodulin localized from 0.28 to 0.47 μm further from the Z-line than the NH2-terminus of nebulin in the various biopsies, indicating that human thin filaments have nebulin-free, pointed-end extensions that comprise up to 34% of total thin-filament length. Furthermore, thin-filament length was negatively correlated with the percentage of type 2X myosin heavy chain within the biopsy and shorter in type 2X myosin heavy chain-positive fibers, establishing the existence of a relationship between thin-filament lengths and fiber types in human muscle. Together, these data challenge the widely held assumption that human thin-filament lengths are constant. Our results also have broad relevance to musculoskeletal modeling, surgical reattachment of muscles, and orthopedic rehabilitation.

Summary Objective Meniscus lesions following trauma or associated with osteoarthritis (OA) have been described, yet meniscus aging has not been systematically analyzed. The objectives of this study were to (1) establish standardized protocols for representative macroscopic and microscopic analysis, (2) improve existing scoring systems, and (3) apply these techniques to a large number of human menisci. Design Medial and lateral menisci from 107 human knees were obtained and cut in two different planes (triangle/cross section and transverse/horizontal section as well) in three separate locations (middle portion, anterior and posterior horns). All sections included vascular and avascular regions and were graded for (1) surface integrity, (2) cellularity, (3) matrix/fiber organization and collagen alignment, and (4) Safranin-O staining intensity. The cartilage in all knee compartments was also scored. Results The new macroscopic and microscopic grading systems showed high inter-reader and intra-reader intraclass correlation coefficients. The major age-related changes in menisci in joints with no or minimal OA included increased Safranin-O staining intensity, decreased cell density, the appearance of acellular zones, and evidence of mucoid degeneration with some loss of collagen fiber organization. The earliest meniscus changes occurred predominantly along the inner rim. Menisci from OA joints showed severe fibrocartilaginous separation of the matrix, extensive fraying, tears and calcification. Abnormal cell arrangements included decreased cellularity, diffuse hypercellularity along with cellular hypertrophy and abnormal cell clusters. In general, the anterior horns of both medial and lateral menisci were less affected by age and OA. Conclusions New standardized protocols and new validated grading systems allowed us to conduct a more systematic evaluation of changes in aging and OA menisci at a macroscopic and microscopic level. Several meniscus abnormalities appear to be specific to aging in the absence of significant OA. With aging the meniscal surface can be intact but abnormal matrix organization and cellularity were observed within the meniscal substance. The increased Safranin-O staining appears to represent a shift from fibroblastic to chondrocytic phenotype during aging and early degeneration.

Background Many patellofemoral complications such as anterior knee pain, subluxation, fracture, wear, and aseptic loosening after total knee arthroplasty are attributed to malrotation of the femoral component. Rotating-platform mobile bearings can reduce malrotation between the tibial and femoral components and may also improve patellofemoral maltracking. Methods A computer model (LifeMOD/KneeSIM) of a weight-bearing deep knee bend was validated using cadaver knees tested in an Oxford-type knee rig. Changes in knee kinematics and patellofemoral forces were measured after femoral component malrotation of ± 3°. The effect of a rotating–bearing on these kinematics and forces was determined. Findings In a fixed-bearing arthroplasty femoral component internal malrotation increased tibiofemoral internal rotation by 3.4°, and external malrotation increased tibiofemoral external rotation by 4°. Femoral component malrotation affected patellofemoral lateral shift by up to 2.5 mm, and patellofemoral lateral shear by up to 19 N. When the malrotated femoral component was tested against a rotating–bearing the change in tibiofemoral rotation and patellofemoral lateral shift was less than 1° and 1 mm respectively. The rotating–bearing reduced peak lateral shear by 7 N and peak medial shear by 17 N. Increasing the conformity of the rotating–bearing reduced changes in tibiofemoral rotation due to femoral malrotation and increased the net rotation of the bearing (by approximately 5°) during flexion. Interpretation Our results are consistent with one randomized clinical outcome study and emphasize the value of computational modeling for preclinical design evaluation. It is important to continue to improve existing methodologies for accurate femoral component alignment especially in rotation.