We compared joint proprioception in 12 hips in 12 patients with hemiarthroplasty after fracture of the hip, in 12 hips in 11 patients with total hip arthroplasty because of osteoarthritis and in a control group of 12 age-matched patients with no clinical complaints. There was no significant difference (p = 0.05) in joint proprioception in any of the groups. There was no decrease in joint proprioception in the group with total hip arthroplasty compared with the hemiarthroplasty group or with the control group. Other factors such as stretch receptors in the adjacent tendons and muscles may have a greater influence on proprioception in the hip than the intracapsular components

Current methods of measurement of proprioceptive function depend on the ability to detect passive movement (kinaesthesia) or the awareness of joint position (joint position sense, JPS). However, reports of proprioceptive function in healthy and pathological joints are quite variable, which may be due to the different methods used. We have compared the validity of several frequently used methods to quantify proprioception. Thirty healthy subjects aged between 24 and 72 years underwent five established tests of proprioception. Two tests were used for the measurement of kinaesthesia (KT1 and KT2). Three tests were used for the measurement of JPS, a passive reproduction test (JPS1), a relative reproduction test (JPS2) and a visual estimation test (JPS3). There was no correlation between the tests for kinaesthesia and JPS or between the different JPS tests. There was, however, a significant correlation between the tests for kinaesthesia (r = 0.86). We conclude therefore that a subject with a given result in one test will not automatically obtain a similar result in another test for proprioception. Since they describe different functional proprioceptive attributes, proprioceptive ability cannot be inferred from independent tests of either kinaesthesia or JPS

Osteoarthritis (OA) is a common cause of chronic pain. Subchondral bone is highly innervated, and bone structural changes directly correlate with pain in OA. Mechanisms underlying skeletal–neural interactions are under-investigated. Bone derived axon guidance molecules are known to regulate bone remodelling. Such signals in the nervous system regulate neural plasticity, branching and neural inflammation. Perturbation of these signals during OA disease progression may disrupt sensory afferents activity, affecting tissue integrity, nociception, and proprioception. Osteocyte mechanical loading and IL-6 stimulation alters axon guidance signalling influencing innervation, proprioception, and nociception. Human Y201 MSC cells, embedded in 3D type I collagen gels (0.05 × 106 cell/gel) in 48 well plastic or silicone (load) plates, were differentiated to osteocytes for 7 days before stimulation with IL-6 (5ng/ml) with soluble IL-6 receptor (sIL-6r (40ng/ml) or unstimulated (n=5/group), or mechanically loaded (5000 μstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). RNA extracted 1hr and 24hrs post load was quantified by RNAseq whole transcriptome analysis (NovaSeq S1 flow cell 2 × 100bp PE reads and differentially expressed neurotransmitters identified (>2-fold change in DEseq2 analysis on normalised count data with FDR p<0.05). After 24 hours, extracted IL-6 stimulated RNA was quantified by RT-qPCR for neurotrophic factors using 2–∆∆Ct method (efficiency=94-106%) normalised to reference gene GAPDH (stability = 1.12 REfinder). Normally distributed data with homogenous variances was analysed by two-tailed t test. All detected axonal guidance genes were regulated by mechanical load. Axonal guidance genes were both down-regulated (Netrin1 0.16-fold, p=0.001; Sema3A 0.4-fold, p<0.001; SEMA3C (0.4-fold, p<0.001), and up-regulated (SLIT2 2.3-fold, p<0.001; CXCL12 5-fold, p<0.001; SEMA3B 13-fold, p<0.001; SEMA4F 2-fold, p<0.001) by mechanical load. IL6 and IL6sR stimulation upregulated SEMA3A (7-fold, p=0.01), its receptor Plexin1 (3-fold, p=0.03). Neutrophins analysed in IL6 stimulated RNA did not show regulation. Here we show osteocytes regulate multiple factors which may influence innervation, nociception, and proprioception upon inflammatory or mechanical insult. Future studies will establish how these factors may combine and affect nerve activity during OA disease progression

Introduction. PIEZO mechanoreceptors are increasingly recognized to play critical roles in fundamental physiological processes like proprioception, touch, or tendon biomechanics. However, their gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective tools to probe these processes. Here, we developed new tailor-made nanoswitches enabling wireless targeted actuation on PIEZO1 by combining molecular imprinting concepts with magnetic systems. Method. Two epitopes from functionally relevant domains of PIEZO1 were rationally selected in silico and used as templates for synthesizing molecularly imprinted nanoparticles (MINPs). Highly-responsive superparamagnetic zinc-doped iron oxide nanoparticles were incorporated into MINPs to grant them magnetic responsiveness. Endothelial cells (ECs) and adipose tissue-derived stem cells (ASCs) incubated with each type of MINP were cultured under or without the application of cyclical magnetomechanical stimulation. Downstream effects of PIEZO1 actuation on cell mechanotransduction signaling and stem cell fate were screened by analyzing gene expression profiles. Result. Nanoswitches showed sub-nanomolar affinity for their respective epitope, binding PIEZO1-expressing ECs similarly to antibodies. Expression of genes downstream of PIEZO1 activity significantly changed after magnetomechanical stimulation, demonstrating that nanoswitches can transduce this stimulus directly to PIEZO1 mechanoreceptors. Moreover, this wireless actuation system proved effective for modulating the expression of genes related to musculoskeletal differentiation pathways in ASCs, with RNA-sequencing showing pronounced shifts in extracellular matrix organization, signal transduction, or collagen biosynthesis and modification. Importantly, targeting each epitope led to different signaling effects, implying distinct roles for each domain in the sophisticated function of these channels. Conclusion. This innovative wireless actuation technology provides a promising approach for dissecting PIEZO-mediated mechanobiology and suggests potential therapeutic applications targeting PIEZO1 in regenerative medicine for mechanosensitive tissues like tendon. Acknowledgements. EU's Horizon 2020 ERC under grant No. 772817 and Horizon Europe under grant No. 101069302; FCT/MCTES for PD/BD/143039/2018, COVID/BD/153025/2022, 10.54499/2020.03410.CEECIND/CP1600/CT0013, 10.54499/2022.05526.PTDC, 10.54499/UIDB/50026/2020, 10.54499/UIDP/50026/2020, and 10.54499/LA/P/0050/2020

Menisci are crucial structures for knee homeostasis: they provide increase of congruence between the articular surfaces of the distal femur and tibial plateau, bear loading, shock absorption, lubrication, and proprioception. After a meniscal lesion, the golden rule, now, is to save as much meniscus as possible: only the meniscus tissue which is identified as unrepairable should be excised and meniscal sutures find more and more indications. Several different methods have been proposed to improve meniscal healing. They include very basic techniques, such as needling, abrasion, trephination and gluing, or more complex methods, such as synovial flaps, meniscal wrapping, or the application of fibrin clots. Basic research of meniscal substitutes has also become very active in the last decades. The features needed for a meniscal scaffold are: promotion of cell migration, it should be biomimetic and biocompatible, it should resist forces applied and transmitted by the knee, it should slowly biodegrade and should be easy to handle and implant. Several materials have been tested, that can be divided into synthetic and biological. The first have the advantage to be manufactured with the desired shapes and sizes and with precise porosity dimension and biomechanical characteristics. To date, the most common polymers are polylactic acid (PGA); poly-(L)-lactic acid (PLLA); poly- (lactic-co-glycolic acid) (PLGA); polyurethane (PU); polyester carbon and polycaprolactone (PCL). The possible complications, more common in synthetic than natural polymers are poor cell adhesion and the possibility of developing a foreign body reaction or aseptic inflammation, leading to alter the joint architecture and consequently to worsen the functional outcomes. The biological materials that have been used over time are the periosteal tissue, the perichondrium, the small intestine submucosa (SIS), acellular porcine meniscal tissue, bacterial cellulose. Although these have a very high biocompatibility, some components are not suitable for tissue engineering as their conformation and mechanical properties cannot be modified. Collagen or proteoglycans are excellent candidates for meniscal engineering, as they maintain a high biocompatibility, they allow for the modification of the porosity texture and size and the adaptation to the patient meniscus shape. On the other hand, they have poor biomechanical characteristics and a more rapid degradation rate, compared to others, which could interfere with the complete replacement by the host tissue. An interesting alternative is represented by hydrogel scaffolds. Their semi-liquid nature allows for the generation of scaffolds with very precise geometries obtained from diagnostic images (i.e. MRI). Promising results have been reported with alginate and polyvinyl alcohol (PVA). Furthermore, hydrogel scaffolds can be enriched with growth factors, platelet-rich plasma (PRP) and Bone Marrow Aspirate Concentrate (BMAC). In recent years, several researchers have developed meniscal scaffolds combining different biomaterials, to optimize the mechanical and biological characteristics of each polymer. For example, biological polymers such as chitosan, collagen and gelatin allow for excellent cellular interactions, on the contrary synthetic polymers guarantee better biomechanical properties and greater reliability in the degradation time. Three-dimensional (3D) printing is a very interesting method for meniscus repair because it allows for a patient-specific customization of the scaffolds. The optimal scaffold should be characterized by many biophysical and biochemical properties as well as bioactivity to ensure an ECM-like microenvironment for cell survival and differentiation and restoration of the anatomical and mechanical properties of the native meniscus. The new technological advances in recent years, such as 3D bioprinting and mesenchymal stem cells management will probably lead to an acceleration in the design, development, and validation of new and effective meniscal substitutes

Meniscus has many important functions in the knee joint such as load bearing, shock absorption, joint stability, joint lubrication and proprioception. In the recent years, meniscus injuries have been the focus of orthopaedic surgeons and musculoskeletal tissue engineering applications because of its avascular nature. In this study, we aimed to compare the regeneration capacities of two composite scaffolds in a New Zealand Rabbit meniscal defect model. The first scaffold consists Poly-Lactic Acid (PLA) + chitosan + loofah and the second PLA + Hydroxyapatite (HAp) + loofah. In order to produce these scaffolds; 4% chitosan, 4% PLA and 4% HAp solutions were seperately prepared. The loofah pieces were saturated with these solutions and vacuum-dried for 14 days and sterilized with ethylene oxide. There were several characterizations performed such as Fourier Transform Infrared Spectroscopy (FTIR) for the investigation of chemical structure, Scanning Electron Microscopy (SEM) for morphological analysis, thermogravimetric differential thermal analysis (TGA/DTA) for thermal properties, mechanical compression and swelling ratio analysis. Moreover, in order to investigate biocompatibility of the scaffolds, WST-1 colorimetric assay at days 3, 7, 10, 14 and 21 was conducted. After these biocompatibility analysis, a 1.5-mm cylindrical defect was created in the avascular portion of the anterior horn of the medial meniscus in 14 New Zealand rabbits (2.5–3 kg weight) which were randomly grouped in two. The scaffolds were implanted at the defect site with the help of a freshly prepared fibrin glue. 8 weeks after the operation, the rabbits were sacrificed and their tissues were kept for further mechanical, radiological and histological analysis. In conclusion, we succeeded to produce a new meniscus scaffold. The proliferation ability of PLA + chitosan + loofah scaffold is higher than PLA + HAp + loofah scaffold. However, there was no statistically significant difference among them

Background. Hip resurfacing arthroplasty (HRA) and total hip arthroplasty (THA) are treatments of end-stage hip disease. Gait analysis studies comparing HRA and THA have demonstrated HRA results in a more normal gait than THA. The reasons may include the larger, more anatomic head diameter, the preservation of the femoral neck with restoration of the anatomical hip centre position and normal proprioception. This study investigated (1)whether femoral head size diameter affects gait; (2)whether gait still differs between THA and HRA patients even with comparable head diameters. Methods. We analysed the gait of 33 controls and 50 patients with unilateral hip replacement. Follow-up ranged from 9–68 months. In 27 hips a small femoral head size was used (≤ 36mm); in 23 hips a large head size (>36mm). The small size group consisted of 11 long femoral stem THA and 16 short-stem THA; the large group of 5 long-stem, 8 short-stem THA and 10 HRA patients. There were 14 females/19 males in the control group; 22 females/5 males in the small size group; 13 females/10 males in the large size group. Results. (1) We found a significant difference in step-length between small head sizes and controls (p<0.01) at speeds ranging from 4.0 to 5.5 km/h but no difference between the larger head size and the controls. There was no significant difference in maximum speed, weight acceptance, push-off, mid-stance, impulse and cadence between the groups. (2)Analysis between THA and HRA in the large head size group revealed a significant difference in maximum speed (p=0.021) between long-stem THA (6.338 km/h± 1.542) and HRA (7.756km/h± 0.7604) patients. At 5.5 km/h there was a significantly better weight acceptance (p=0.009) and mid-stance (p=0.041) of HRA compared to short-stems. Impulse was significantly higher for HRA compared to long-stem THA (p<0.05) at all speeds ranging 4 to 5.5 km/h. (3)Males (7.1972 km/h ± .9700) had significantly higher maximum speeds compared to females (6.6524km/h± 1.019) (p=0.017) and lower gait impulse (p<0.01) at speeds ranging from 4 to 5.5km/h. (4)There was no significant difference in Oxford Hip Score (OHS) and EQ-5D of patients in the small compared to large head size group. Conclusions. Gait analysis demonstrated a significant difference in step length between THA patients with head size ≤ 36mm and normal controls. There was no difference in step length between normal controls and THA patients with larger head sizes. Compared to larger head size THA, HRA still revealed higher maximum speeds and better weight acceptance. Males had significantly higher maximum speeds compared to females (controls and hip replacement patients). We could not demonstrate a correlation between better gait and Oxford scores or EQ-5D scores but these are known to have a ceiling effect. In a former study, better gait parameters such as longer step length and higher maximum speed have been associated with higher patient satisfaction

Three palmar wrist ligaments from fresh human cadavers were dissected from the proximal to the distal insertions and stained to identify the mechanoreceptors. Golgi organs, Pacinian corpuscles, Ruffini endings and free nerve endings were present in all three ligaments. In the radial collateral and radiolunate ligaments they were found in increased density towards the proximal and distal insertions. A more uniform distribution was found in the radioscaphocapitate ligament which has attachments to three bones. The palmar wrist ligaments may have a significant sensory role in maintaining the stability of the wrist and in controlling its movement. Although technically difficult, the surgical repair of traumatic wrist defects should attempt to preserve the innervation of the ligaments, shown to be mainly near bony attachments. This may allow improvement in postoperative outcomes by preserving some proprioception. In some painful post-traumatic or degenerative conditions, however, denervation may be advantageous

Immobilisation causes denervation-like changes in the motor endplates, decreases the content of IGF-I, and increases the number of IGF-I receptors in the spinal cord. In the rat we investigated whether similar changes occur after a fracture of the midshaft of the femur which had been treated by intramedullary fixation with adequate or undersized pins. A more pronounced reduction in muscle wet weight was seen after fixation by undersized pins as well as decreased ash density of the ipsilateral tibia which did not completely return to normal within the 12-week experimental period. The nicotinic cholinergic receptors in the motor endplates of tibialis anterior were increased (p < 0.01) and there was a significant increase (p < 0.02) in IGF-I receptors in the lumbar spinal cord ipsilateral to the fracture after treatment by undersized nails. These changes may be associated with the impaired proprioception, co-ordination and motor activity which are sometimes seen after fractures

In order to determine the potential for an internervous safe zone, 20 hips from human cadavers were dissected to map out the precise pattern of innervation of the hip capsule. The results were illustrated in the form of a clock face. The reference point for measurement was the inferior acetabular notch, representing six o’clock. Capsular branches from between five and seven nerves contributed to each hip joint, and were found to innervate the capsule in a relatively constant pattern. An internervous safe zone was identified anterosuperiorly in an arc of 45° between the positions of one o’clock and half past two.

Our study shows that there is an internervous zone that could be safely used in a capsule-retaining anterior, anterolateral or lateral approach to the hip, or during portal placement in hip arthroscopy.

The success of long-term transcutaneous implants depends on dermal attachment to prevent downgrowth of the epithelium and infection. Hydroxyapatite (HA) coatings and fibronectin (Fn) have independently been shown to regulate fibroblast activity and improve attachment. In an attempt to enhance this phenomenon we adsorbed Fn onto HA-coated substrates. Our study was designed to test the hypothesis that adsorption of Fn onto HA produces a surface that will increase the attachment of dermal fibroblasts better than HA alone or titanium alloy controls.

Iodinated Fn was used to investigate the durability of the protein coating and a bioassay using human dermal fibroblasts was performed to assess the effects of the coating on cell attachment. Cell attachment data were compared with those for HA alone and titanium alloy controls at one, four and 24 hours. Protein attachment peaked within one hour of incubation and the maximum binding efficiency was achieved with an initial droplet of 1000 ng. We showed that after 24 hours one-fifth of the initial Fn coating remained on the substrates, and this resulted in a significant, three-, four-, and sevenfold increase in dermal fibroblast attachment strength compared to uncoated controls at one, four and 24 hours, respectively.