Function and strain of the anterolateral ligament part II: reconstruction.

PURPOSE: Anterolateral rotatory instability (ALRI) may result from isolated ruptures of the anterior cruciate ligament (ACL) or combined lesions with the anterolateral ligament (ALL). Biomechanical studies have demonstrated that the ALL contributes to the overall rotational stability of the knee. The purpose of this study was to investigate the biomechanical function of anatomic ALL reconstruction (ALLrec) in the setting of a combined ACL and ALL injury and reconstruction. The hypothesis was that combined ACL reconstruction (ACLrec) and ALLrec (ACL/ALLrec) significantly reduces internal rotation and shows load sharing between both reconstructions compared with isolated ACLrec. METHODS: Eight fresh-frozen cadaveric knees were evaluated using a six degrees of freedom knee simulator. Continuous passive motion and external loads were tested. Kinematic differences between ACLrec and combined ACL/ALLrec were compared. Additionally, ACL graft tension and ALL graft strain were measured continuously throughout the testing protocol. RESULTS: Combined anatomic ACL/ALLrec significantly improved the internal rotatory stability compared with isolated ACLrec at 30°-90° under an internal rotation moment. During a static pivot-shift test, additional ALLrec showed no significant reduction of ap-translation. ALLrec resulted in an increase in ACL graft tension during continuous passive motion and with additional internal rotation moment. CONCLUSION: In the case of a combined ACL and ALL deficiency, concurrent ACLrec and ALLrec significantly improved the rotatory stability of the knee compared with solely reconstructing the ACL at flexion angles ≥ 30°. Nevertheless, additional ALLrec with fixation at 60° and with low tension could not restore extension-near rotatory stability. For that reason, ALLrec with fixation at 60° flexion cannot be recommended in clinical application.

Are Knotted or Knotless Techniques Better for Reconstruction of Full-Thickness Tears of the Superior Portion of the Subscapularis Tendon? A Study in Cadavers.

BACKGROUND: Knotted and knotless single-anchor reconstruction techniques are frequently performed to reconstruct full-thickness tears of the upper portion of subscapularis tendon. However, it is unclear whether one technique is superior to the other. QUESTIONS/PURPOSES: (1) When comparing knotless and knotted single-anchor reconstruction techniques in full-thickness tears of the upper subscapularis tendon, is there a difference in stiffness under cyclic load? (2) Are there differences in cyclic gapping between knotless and knotted reconstructions? (3) Are there differences in the maximal stiffness, yield load, and ultimate load to failure? (4) What are the modes of failure of knotless and knotted reconstruction techniques? METHODS: Eight matched pairs of human cadaveric shoulders were dissected, and a full-thickness tear of the subscapularis tendon (Grade 3 according to the Fox and Romeo classification) was created. The cadavers all were male specimens, with a median (range) age of 69 years (61 to 75). Before biomechanical evaluation, the specimens were randomized into two equal reconstruction groups: knotless single anchor and knotted single anchor. All surgical procedures were performed by a single orthopaedic surgeon who subspecializes in sports orthopedics and shoulder surgery. With a customized set up that was integrated in a dynamic material testing machine, the humeri were consecutively loaded from 10 N to 60 N, from 10 N to 100 N, and from 10 N to 180 N for 50 cycles. Furthermore, the gapping behavior of the tear was analyzed using a video tracking system. Finally, the stiffness, gapping, maximal stiffness, yield loads, and maximum failure loads of both reconstruction groups were statistically analyzed. Failure was defined as retearing of the reconstructed gap threshold due to rupture of the tendon and/or failure of the knots or anchors. After biomechanical testing, bone quality was measured at the footprint of the subscapularis using microCT in all specimens. Bone quality was equal between both groups. To detect a minimum 0.15-mm difference in gap formation between the two repair techniques (with a 5% level of significance; α = 0.05), eight matched pairs (n = 16 in total) were calculated as necessary to achieve a power of at least 90%. RESULTS: The first study question can be answered as follows: for stiffness under cyclic load, there were no differences with the numbers available between the knotted and knotless groups at load stages of 10 N to 60 N (32.7 ± 3.5 N/mm versus 34.2 ± 5.6 N/mm, mean difference 1.5 N/mm [95% CI -6.43 to 3.33]; p = 0.55), 10 N to 100 N (45.0 ± 4.8 N/mm versus 45.2 ± 6.0 N/mm, mean difference 0.2 N/mm [95% CI -5.74 to 6.04]; p = 0.95), and 10 N to 180 N (58.2 ± 10.6 N/mm versus 55.2 ± 4.7 N/mm, mean difference 3 N/mm [95% CI -5.84 to 11.79]; p = 0.48). In relation to the second research question, the following results emerged: For cyclic gapping, there were no differences between the knotted and knotless groups at any load levels. The present study was able to show the following with regard to the third research question: Between knotted and knotless repairs, there were no differences in maximal load stiffness (45.3 ± 8.6 N/mm versus 43.5 ± 10.2 N/mm, mean difference 1.8 [95% CI -11.78 to 8.23]; p = 0.71), yield load (425.1 ± 251.4 N versus 379.0 ± 169.4 N, mean difference 46.1 [95% CI -276.02 to 183.72]; p = 0.67), and failure load (521.1 ± 266.2 N versus 475.8 ± 183.3 N, mean difference 45.3 [95% CI -290.42 to 199.79]; p = 0.69). Regarding the fourth question concerning the failure modes, in the knotted repairs, the anchor tore from the bone in 2 of 8, the suture tore from the tendon in 6 of 8, and no suture slipped from the eyelet; in the knotless repairs, the anchor tore from the bone in 2 of 8, the suture tore from the tendon in 3 of 8, and the threads slipped from the eyelet in 3 of 8. CONCLUSION: With the numbers available, we found no differences between single-anchor knotless and knotted reconstruction techniques used to repair full-thickness tears of the upper portion of subscapularis tendon. CLINICAL RELEVANCE: The reconstruction techniques we analyzed showed no differences in terms of their primary stability and biomechanical properties at the time of initial repair and with the numbers available. In view of these experimental results, it would be useful to conduct a clinical study in the future to verify the translationality of the experimental data of the present study.

Biomechanics of a cemented short stem: a comparative in vitro study regarding primary stability and maximum fracture load.

PURPOSE: In total hip arthroplasty, uncemented short stems have been used more and more frequently in recent years. Especially for short and curved femoral implants, bone-preserving and soft tissue-sparing properties are postulated. However, indication is limited to sufficient bone quality. At present, there are no curved short stems available which are based on cemented fixation. METHODS: In this in vitro study, primary stability and maximum fracture load of a newly developed cemented short-stem implant was evaluated in comparison to an already well-established cemented conventional straight stem using six pairs of human cadaver femurs with minor bone quality. Primary stability, including reversible micromotion and irreversible migration, was assessed in a dynamic material-testing machine. Furthermore, a subsequent load-to-failure test revealed the periprosthetic fracture characteristics. RESULTS: Reversible and irreversible micromotions showed no statistical difference between the two investigated stems. All short stems fractured under maximum load according to Vancouver type B3, whereas 4 out of 6 conventional stems suffered a periprosthetic fracture according to Vancouver type C. Mean fracture load of the short stems was 3062 N versus 3160 N for the conventional stems (p = 0.84). CONCLUSION: Primary stability of the cemented short stem was not negatively influenced compared to the cemented conventional stem and no significant difference in fracture load was observed. However, a clear difference in the fracture pattern has been identified.

Newly Defined ATP-Binding Cassette Subfamily B Member 5 Positive Dermal Mesenchymal Stem Cells Promote Healing of Chronic Iron-Overload Wounds via Secretion of Interleukin-1 Receptor Antagonist.

In this study, we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of nonhealing wounds. Local administration of dermal ABCB5+ -derived mesenchymal stem cells (MSCs) attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wounds in the iron-overload mouse model mimicking the nonhealing state of human venous leg ulcers. The observed beneficial effects were due to interleukin-1 receptor antagonist (IL-1RA) secreted by ABCB5+ -derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained proinflammatory M1 macrophages toward repair promoting anti-inflammatory M2 macrophages at the wound site. The beneficial anti-inflammatory effect of IL-1RA released from ABCB5+ -derived MSCs on human wound macrophages was conserved in humanized NOD-scid IL2rγ null mice. In conclusion, human dermal ABCB5+ cells represent a novel, easily accessible, and marker-enriched source of MSCs, which holds substantial promise to successfully treat chronic nonhealing wounds in humans. Stem Cells 2019;37:1057-1074.

Biomechanical considerations are crucial for the success of tendon and meniscus allograft integration-a systematic review.

PURPOSE: This systematic review intends to give an overview of the current knowledge on how allografts used for the reconstruction of cruciate ligaments and menisci are integrated and specifically perform regarding their biomechanical function. METHODS: Two reviewers reviewed the PubMed and Central Cochrane library with focus on the biomechanical integration of tendon ligament and meniscus allografts. The literature search was conducted in accordance with the PRISMA statement for reporting systematic reviews and meta-analyses. RESULTS: The analysed literature on tendon allografts shows that they are more vulnerable to overstretching in the phase of degradation compared to autografts as the revascularization process starts later and takes longer. Therefore, to avoid excessive graft loads, allografts for cruciate ligament replacement should be selected that exhibit much higher failure loads than the native ligaments to counteract the detrimental effect of degradation. Further, placement techniques should be considered that result in a minimum of strain differences during knee joint motion, which is best achieved by near-isometric placement. The most important biomechanical parameters for meniscus allograft transplantation are secure fixation and proper graft sizing. Allograft attachment by bone plugs or by a bone block is superior to circumferential suturing and enables the allograft to restore the chondroprotective biomechanical function. Graft sizing is also of major relevance, because too small grafts are not able to compensate the knee joint incongruity and too large grafts may fail due to extrusion. Only adequate sizing and fixation together can lead to a biomechanically functioning allograft. The objective assessment of the biomechanical quality of allografts in a clinical setting is challenging, but would be highly desirable for monitoring the remodelling and incorporation process. CONCLUSIONS: Currently, indicators like ap-stability after ACL reconstruction or meniscal extrusion represent only indirect measures for biomechanical graft integration. These parameters are at best clinical indicators of allograft function, but the overall integration properties comprising e.g. fixation and graft stiffness remain unknown. Therefore, future research should e.g. focus on advanced imaging techniques or other non-invasive methods allowing for in vivo assessment of biomechanical allograft properties.

Release of the medial collateral ligament is mandatory in medial open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to quantify the effect of clinically relevant open-wedge high tibial osteotomies on medial collateral ligament (MCL) strain and the resultant tibiofemoral contact mechanics during knee extension and 30° knee flexion. METHODS: Six human cadaveric knee joints were axially loaded (1 kN) in knee extension and 30° knee flexion. Strains at the anterior and posterior regions of the MCL were determined using strain gauges. Tibiofemoral contact mechanics (contact area, mean and maximum contact pressure) were investigated using pressure-sensitive sensors. Open-wedge osteotomy was performed using biplanar cuts and osteotomy angles of 5° and 10° were maintained using an external fixator. Tests were performed first with intact and then with dissected MCL. RESULTS: Nonparametric statistical analyses indicated a significant strain increase (p < 0.01) in the anterior and posterior fibres of the MCL with increasing osteotomy angle of up to 8.3% and 6.0%, respectively. Only after releasing the MCL the desired lateralisation of the mechanical axis was achieved, indicating a significant decrease in the maximum contact pressure in knee extension of - 25% (p = 0.028) and 30° knee flexion of - 21% (p = 0.027). CONCLUSIONS: The results of the present biomechanical study suggest, that an open-wedge high tibial osteotomy is most effective in reducing the medial contact pressure when spreading the osteotomy to 10° and concomitantly releasing the MCL. To transfer the results of this biomechanical study to the clinical day-to-day practice, it is necessary to factor in the individual ligamentous laxity of each patient into the treatment options e.g. particularly for patients with distinct knee ligament laxity or medial ligamentary instability, the release of the MCL should be performed with care. LEVEL OF EVIDENCE: Controlled laboratory study.

Analysis of human menisci degeneration via infrared attenuated total reflection spectroscopy.

Degeneration of human meniscal tissue induces impairment of normal knee functions, and is a highly relevant etiology of knee joint tears and osteoarthritis. Currently, the grading scale of meniscus degeneration is conventionally derived from evaluating meniscal morphology and histological staining. However, mid-infrared attenuated total reflectance (IR-ATR) spectroscopy is a particularly useful technique that may analyze the biomolecular composition at a sample surface, and provide information on the intra- and/or inter-molecular chemical bonds. In the present study, 61 lyophilized human menisci samples at different grades of degeneration were analyzed via IR-ATR spectroscopy in a label-free fashion, and the data were evaluated via Gaussian peak fitting and 2D correlation analysis. During increasing meniscal degeneration (i.e., grade 1 to 4) along with calcification at grade 4, an evident blue shift of the amide I band (1700-1600 cm-1) was observed in the associated IR spectra. In addition, Gaussian peak fitting revealed significant area variance of the fitted sub-peaks. 2D correlation spectra provided further access to detailed changes of the amide I band during the degeneration process. Derived from this multi-tiered data analysis taking into account the protein secondary structure information within the amide I band, and the triple helical structure of meniscal collagen, the blue shift and peak area changes during meniscus degeneration are indicative of collagen fibril formation during evolving degeneration. Furthermore, a degradation of the water-binding proteoglycan and collagen network especially for degenerated menisci with calcification was observed. Results were compared with a collagen-chondroitin sulphate mixture model, confirming the observed changes in collagen fibrils and proteoglycans. In summary, this study confirms the utility of IR-ATR spectroscopy as a versatile tool providing access to meniscal tissue degeneration processes at molecular level detail, and may in future evolve into a useful diagnostic instrument for analyzing cartilage degeneration.

Correction to: In vivo performance of a novel silk fibroin scaffold for partial meniscal replacement in a sheep model.

The author would like to correct the errors in the publication of the original article. The corrected details are given below for your reading.

Function and strain of the anterolateral ligament part I: biomechanical analysis.

PURPOSE: Because reconstruction of the anterior cruciate ligament (ACL) in a double-bundle technique did not solve the problem of persistent rotatory laxity after surgery, new potential answers to this issue are of great interest. One of these is an extraarticular stabilization based on the rediscovery of the anterolateral ligament (ALL). Knowledge about its biomechanical function and benchmark data for an optimal reconstruction remain lacking. Therefore, the purpose of this study was to assess the function of the ALL under passive motion, anterior tibial translation and tibial rotational moments. METHODS: Continuous passive motion (0°-120° flexion), ap-translation and static pivot shift tests were performed on eight cadaveric knees. The knees were measured in intact, ACL-resected (ACLres) and ACL + ALL-resected (ALLres) conditions. Ap-translation and static pivot shift under 134 N anterior shear load were determined at 0°, 30°, 60° and 90° flexion. Strain of the ALL was recorded in intact and ACLres conditions. RESULTS: During continuous passive motion under unloaded conditions, no significant difference in internal rotation between ACLres and ALLres was observed. With an additional internal tibial torque of 1-4 Nm, internal rotation increased significantly between 60° and 120° after resection of the ALL (p ≤ 0.05). Anterior tibial translation was significantly higher at 30° in ALLres (p = 0.01) and for a simulated pivot shift at 60° and 90° in ACLres (p ≤ 0.01). The ALL was not strained under unloaded passive motion. Adding different internal tibial torques led to strain starting at 60° flexion (1 N m internal torque) and 15° flexion (4 N m internal torque) in intact ligaments. In ACLres, significantly greater ALL strains under lower flexion angles were seen for each condition (p ≤ 0.05). CONCLUSIONS: This study demonstrated the ALL to be without function under passive motion and with no influence on tibial rotation. On application of extrinsic loads, the ALL had a low but significant stabilizing effect against anterior tibial shear load at low flexion angles. For this reason, it can be concluded that the ALL is supporting the ACL against internal tibial loads to a minor degree. A relationship between the ALL and the pivot shift cannot be concluded. With these results ALL-reconstruction cannot be recommended at the moment without further biomechanical investigations.

ACL double-bundle reconstruction with one tibial tunnel provides equal stability compared to two tibial tunnels.

PURPOSE: The purpose of this study was to investigate whether an anterior cruciate ligament (ACL) double-bundle reconstruction with one tibial tunnel displays the same in vitro stability as a conventional double-bundle reconstruction with two tibial tunnels when using the same tensioning protocol. METHODS: In 11 fresh-frozen cadaveric knees, ACL double-bundle reconstruction with one and two tibial tunnels was performed. The two grafts were tightened using 80 N in different flexion angles (anteromedial-bundle at 60° and posterolateral-bundle at 15°). Anterior tibial translation (134 N) and translation with combined rotatory and valgus loads (10 Nm valgus stress and 4 Nm internal tibial torque) were determined at 0°, 30°, 60° and 90° flexion. Measurements were taken in intact ACL, resected ACL, three-tunnel reconstruction and four-tunnel reconstruction. Additionally, the tension on the grafts was determined. Student's t test was performed for statistical analysis of the related samples. Significance was set at p < 0.017 according to Bonferroni correction. RESULTS: The two reconstructive techniques displayed no significant differences in comparison with the intact ACL in anterior tibial translation at 0°, 60° and 90° of flexion. The same results were obtained for the anterior tibial translation with a combined rotatory load at 60° and 90°. When directly comparing both reconstructive techniques, there were no significant differences for the anterior tibial translation and combined rotatory load at all flexion angles. The measured tension on grafts displayed similar load sharing between both bundles. Except at full extension, both grafts displayed a significantly different tension increase under anterior tibial translation for both techniques (p = 0.0086). CONCLUSIONS: Tightening both bundles in ACL double-bundle reconstruction with one or two tibial tunnels in different flexion angles achieved comparable restoration of stability, although there was different load sharing on the bundles. With regard to individualized ACL reconstruction, the double-bundle technique with one tibial tunnel offers a possibility to address small tibial insertion sites without compromising the advantages of a double-bundle procedure.

Impaired extracellular matrix structure resulting from malnutrition in ovariectomized mature rats.

Bone loss is a symptom related to disease and age, which reflects on bone cells and ECM. Discrepant regulation affects cell proliferation and ECM localization. Rat model of osteoporosis (OVX) was investigated against control rats (Sham) at young and old ages. Biophysical, histological and molecular techniques were implemented to examine the underlying cellular and extracellular matrix changes and to assess the mechanisms contributing to bone loss in the context of aging and the widely used osteoporotic models in rats. Bone loss exhibited a compromised function of bone cells and infiltration of adipocytes into bone marrow. However, the expression of genes regulating collagen catabolic process and adipogenesis was chronologically shifted in diseased bone in comparison with aged bone. The data showed the involvement of Wnt signaling inhibition in adipogenesis and bone loss due to over-expression of SOST in both diseased and aged bone. Further, in the OVX animals, an integrin-mediated ERK activation indicated the role of MAPK in osteoblastogenesis and adipogenesis. The increased PTH levels due to calcium and estrogen deficiency activated osteoblastogenesis. Thusly, RANKL-mediated osteoclastogenesis was initiated. Interestingly, the data show the role of MEPE regulating osteoclast-mediated resorption at late stages in osteoporotic bone. The interplay between ECM and bone cells change tissue microstructure and properties. The involvement of Wnt and MAPK pathways in activating cell proliferation has intriguing similarities to oncogenesis and myeloma. The study indicates the importance of targeting both pathways simultaneously to remedy metabolic bone diseases and age-related bone loss.

Bone matrix, cellularity, and structural changes in a rat model with high-turnover osteoporosis induced by combined ovariectomy and a multiple-deficient diet.

In estrogen-deficient, postmenopausal women, vitamin D and calcium deficiency increase osteoporotic fracture risk. Therefore, a new rat model of combined ovariectomy and multiple-deficient diet was established to mimic human postmenopausal osteoporotic conditions under nutrient deficiency. Sprague-Dawley rats were untreated (control), laparatomized (sham), or ovariectomized and received a deficient diet (OVX-Diet). Multiple analyses involving structure (micro-computed tomography and biomechanics), cellularity (osteoblasts and osteoclasts), bone matrix (mRNA expression and IHC), and mineralization were investigated for a detailed characterization of osteoporosis. The study involved long-term observation up to 14 months (M14) after laparotomy or after OVX-Diet, with intermediate time points at M3 and M12. OVX-Diet rats showed enhanced osteoblastogenesis and osteoclastogenesis. Bone matrix markers (biglycan, COL1A1, tenascin C, and fibronectin) and low-density lipoprotein-5 (bone mass marker) were down-regulated at M12 in OVX-Diet rats. However, up-regulation of matrix markers and existence of unmineralized osteoid were seen at M3 and M14. Osteoclast markers (matrix metallopeptidase 9 and cathepsin K) were up-regulated at M14. Micro-computed tomography and biomechanics confirmed bone fragility of OVX-Diet rats, and quantitative RT-PCR revealed a higher turnover rate in the humerus than in lumbar vertebrae, suggesting enhanced bone formation and resorption in OVX-Diet rats. Such bone remodeling caused disturbed bone mineralization and severe bone loss, as reported in patients with high-turnover, postmenopausal osteoporosis. Therefore, this rat model may serve as a suitable tool to evaluate osteoporotic drugs and new biomaterials or fracture implants.

Small changes in bone structure of female α7 nicotinic acetylcholine receptor knockout mice.

BACKGROUND: Recently, analysis of bone from knockout mice identified muscarinic acetylcholine receptor subtype M3 (mAChR M3) and nicotinic acetylcholine receptor (nAChR) subunit α2 as positive regulator of bone mass accrual whereas of male mice deficient for α7-nAChR (α7KO) did not reveal impact in regulation of bone remodeling. Since female sex hormones are involved in fair coordination of osteoblast bone formation and osteoclast bone degradation we assigned the current study to analyze bone strength, composition and microarchitecture of female α7KO compared to their corresponding wild-type mice (α7WT). METHODS: Vertebrae and long bones of female 16-week-old α7KO (n = 10) and α7WT (n = 8) were extracted and analyzed by means of histological, radiological, biomechanical, cell- and molecular methods as well as time of flight secondary ion mass spectrometry (ToF-SIMS) and transmission electron microscopy (TEM). RESULTS: Bone of female α7KO revealed a significant increase in bending stiffness (p < 0.05) and cortical thickness (p < 0.05) compared to α7WT, whereas gene expression of osteoclast marker cathepsin K was declined. ToF-SIMS analysis detected a decrease in trabecular calcium content and an increase in C4H6N(+) (p < 0.05) and C4H8N(+) (p < 0.001) collagen fragments whereas a loss of osteoid was found by means of TEM. CONCLUSIONS: Our results on female α7KO bone identified differences in bone strength and composition. In addition, we could demonstrate that α7-nAChRs are involved in regulation of bone remodelling. In contrast to mAChR M3 and nAChR subunit α2 the α7-nAChR favours reduction of bone strength thereby showing similar effects as α7ß2-nAChR in male mice. nAChR are able to form heteropentameric receptors containing α- and ß-subunits as well as the subunits α7 can be arranged as homopentameric cation channel. The different effects of homopentameric and heteropentameric α7-nAChR on bone need to be analysed in future studies as well as gender effects of cholinergic receptors on bone homeostasis.

Influence of partial meniscectomy on attachment forces, superficial strain and contact mechanics in porcine knee joints.

PURPOSE: Numerous studies investigated the reasons for premature osteoarthritis due to partial meniscectomy (PM). However, the influence of meniscectomy on attachment forces and superficial strain of the tibial meniscus is unclear. It is hypothesised that these parameters depend on the degree of PM. METHODS: Six porcine medial menisci were placed in a custom made apparatus, and each meniscal attachment was connected to a force sensor. After printing markers onto the tibial meniscal surfaces, the menisci were positioned on a glass plate enabling optical superficial strain measurement. Additionally, contact area and pressure were investigated. Each meniscus was axially loaded up to 650 N using its respective femoral condyle. Testing was conducted intact and after 50 and 75% PM of the posterior horn and extending 75% PM to the anterior horn. RESULTS: With increasing meniscectomy, the attachment forces decreased anteriorly by up to 17% (n.s.) and posteriorly by up to 55% (p = 0.003). The circumferential strain in the peripheral meniscal zones was not affected by the meniscectomy, while in some meniscal zones the radial strain changed from compression to tension. Contact area decreased by up to 23% (p = 0.01), resulting in an increase in 40% (p = 0.02) for the maximum contact pressure. CONCLUSION: Partial meniscectomy significantly alters the loading situation of the meniscus and its attachments. Specifically, the attachment forces decreased with increasing amount of meniscal tissue loss, which reflects the impaired ability of the meniscus to transform axial joint load into meniscal hoop stress.

In vivo performance of a novel silk fibroin scaffold for partial meniscal replacement in a sheep model.

PURPOSE: Due to the negative effects of meniscectomy, there is a need for an adequate material to replace damaged meniscal tissue. To date, no material tested has been able to replace the meniscus sufficiently. Therefore, a new silk fibroin scaffold was investigated in an in vivo sheep model. METHODS: Partial meniscectomy was carried out to the medial meniscus of 28 sheep, and a scaffold was implanted in 19 menisci (3-month scaffold group, n = 9; 6-month scaffold group, n = 10). In 9 sheep, the defect remained empty (partial meniscectomy group). Sham operation was performed in 9 animals. RESULTS: The silk scaffold was able to withstand the loads experienced during the implantation period. It caused no inflammatory reaction in the joint 6 months postoperatively, and there were no significant differences in cartilage degeneration between the scaffold and sham groups. The compressive properties of the scaffold approached those of meniscal tissue. However, the scaffolds were not always stably fixed in the defect, leading to gapping between implant and host tissue or to total loss of the implant in 3 of 9 cases in each scaffold group. Hence, the fixation technique needs to be improved to achieve a better integration into the host tissue, and the long-term performance of the scaffolds should be further investigated. CONCLUSION: These first in vivo results on a new silk fibroin scaffold provide the basis for further meniscal implant development. Whilst more data are required, there is preliminary evidence of chondroprotective properties, and the compressive properties and biocompatibility are promising.

Medial meniscal displacement and strain in three dimensions under compressive loads: MR assessment.

PURPOSE: To investigate the 3D displacement and the local strain of the medial meniscus and its attachments under compressive loading. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) scans of six porcine knee joints were performed under unloaded and loaded conditions (100% and 200% body weight [BW]). Volumes were registered to obtain a 3D displacement field of the medial meniscus and its attachments, which were divided into five anatomic compartments. Finally, displacements of the center of mass of each compartment and the local strain were analyzed. RESULTS: The meniscus and its attachments significantly displaced by up to 2.6 ± 1.2 mm (P < 0.01) under knee joint loads of 200% BW. An increase of 0.9 mm in the distance between posterior and anterior horn (P < 0.001) was observed. The meniscus and its attachment showed an average radial stretch of 0.6%, an average circumferential stretch of 0.9%, and an average axial compression of 11.6% at 200% BW. CONCLUSION: High-resolution MRI was successfully combined with image registration to investigate the displacement and strain of the meniscus and its attachments under compression. The results of this study contribute to the basic understanding of meniscal movement which may impact the design of meniscal implants and the validation of finite element models in the future.

Non-invasive regional parameter identification of degenerated human meniscus.

Accurate identification of local changes in the biomechanical properties of the normal and degenerative meniscus is critical to better understand knee joint osteoarthritis onset and progression. Ex-vivo material characterization is typically performed on specimens obtained from different locations, compromising the tissue's structural integrity and thus altering its mechanical behavior. Therefore, the aim of this in-silico study was to establish a non-invasive method to determine the region-specific material properties of the degenerated human meniscus. In a previous experimental magnetic resonance imaging (MRI) study, the spatial displacement of the meniscus and its root attachments in mildly degenerated (n = 12) and severely degenerated (n = 12) cadaveric knee joints was determined under controlled subject-specific axial joint loading. To simulate the experimental response of the lateral and medial menisci, individual finite element models were created utilizing a transverse isotropic hyper-poroelastic constitutive material formulation. The superficial displacements were applied to the individual models to calculate the femoral reaction force in an inverse finite element analysis. During particle swarm optimization, the four most sensitive material parameters were varied to minimize the error between the femoral reaction force and the force applied in the MRI loading experiment. Individual global and regional parameter sets were identified. In addition to in-depth model verification, prediction errors were determined to quantify the reliability of the identified parameter sets. Both compressibility of the solid meniscus matrix (+141 %, p ≤ 0.04) and hydraulic permeability (+53 %, p ≤ 0.04) were significantly increased in the menisci of severely degenerated knees compared to mildly degenerated knees, irrespective of the meniscus region. By contrast, tensile and shear properties were unaffected by progressive knee joint degeneration. Overall, the optimization procedure resulted in reliable and robust parameter sets, as evidenced by mean prediction errors of <1 %. In conclusion, the proposed approach demonstrated high potential for application in clinical practice, where it might provide a non-invasive diagnostic tool for the early detection of osteoarthritic changes within the knee joint.

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral, microarchitectural, biomechanical and matrix properties of rat bone.

Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid-postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized-steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below -2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.

Free-floating medial meniscus implant kinematics do not change after simulation of medial open-wedge high tibial osteotomy and notchplasty.

PURPOSE: The purpose of this in-vitro study was to examine the kinematics of an artificial, free-floating medial meniscus replacement device under dynamic loading situations and different knee joint states. METHODS: A dynamic knee simulator was used to perform dynamic loading exercises on three neutrally aligned and three 10° valgus aligned (simulating a medial openwedge high tibial osteotomy - MOWHTO) left human cadaveric knee joints. The knee joints were tested in three states (intact, conventional notchplasty, extended notchplasty) while 11 randomised exercises were simulated (jump landing, squatting, tibial rotation and axial ground impacts at 10°, 30° and 60° knee joint flexion) to investigate the knee joint and implant kinematics by means of rigidly attached reflective marker sets and an according motion analysis. RESULTS: The maximum implant translation relative to the tibial plateau was < 13 mm and the maximum implant rotation was < 19° for all exercises. Both, the notchplasties and the valgus knee alignment did not affect the device kinematics. CONCLUSIONS: The results of the present in-vitro study showed that the non-anchored free-floating device remains within the medial knee joint gap under challenging dynamic loading situations without indicating any luxation tendencies. This also provides initial benchtop evidence that the device offers suitable stability and kinematic behaviour to be considered a potential alternative to meniscus allograft transplantation in combination with an MOWHTO, potentially expanding the patient collective in the future.

Effects of mechanical strain on human mesenchymal stem cells and ligament fibroblasts in a textured poly(L-lactide) scaffold for ligament tissue engineering.

The purpose of this study was to prove the effect of cyclic uniaxial intermittent strain on the mRNA expression of ligament-specific marker genes in human mesenchymal stem cells (MSC) and anterior cruciate ligament-derived fibroblasts (ACL-fibroblasts) seeded onto a novel textured poly(L-lactide) scaffold (PLA scaffold). Cell-seeded scaffolds were mechanically stimulated by cyclic uniaxial stretching. The expression of ligament matrix gene markers: collagen types I and III, fibronectin, tenascin C and decorin, as well as the proteolytic enzymes matrix metalloproteinase MMP-1 and MMP-2 and their tissue specific inhibitors TIMP-1 and TIMP-2 was investigated by analysing the mRNA expression using reverse transcriptase polymerase chain reaction and related to the static control. In ACL-fibroblasts seeded on PLA, mechanical load induced up-regulation of collagen types I and III, fibronectin and tenascin C. No effect of mechanical stimulation on the expression of ligament marker genes was found in undifferentiated MSC seeded on PLA. The results indicated that the new textured PLA scaffold could transfer the mechanical load to the ACL-fibroblasts and improved their ligament phenotype. This scaffold might be suitable as a cell-carrying component of ACL prostheses.