In the context of a large animal model of early osteoarthritis (OA) treated by orthobiologics, the purpose of this study was to reveal relations between articular tissues structure/composition and ...cartilage viscoelasticity. Twenty-four sheep, with induced knee OA, were treated by mesenchymal stem cells in various preparations—adipose-derived mesenchymal stem cells (ADSCs), stromal vascular fraction (SVF), and amniotic endothelial cells (AECs)—and euthanized at 3 or 6 months to evaluate the (i) biochemistry of synovial fluid; (ii) histology, immunohistochemistry, and histomorphometry of articular cartilage; and (iii) viscoelasticity of articular cartilage. After performing an initial analysis to evaluate the correlation and multicollinearity between the investigated variables, this study used machine learning (ML) models—Variable Selection Using Random Forests (VSURF) and Extreme Gradient Boosting (XGB)—to classify variables according to their importance and employ them for interpretation and prediction. The experimental setup revealed a potential relation between cartilage elastic modulus and cartilage thickness (CT), synovial fluid interleukin 6 (IL6), and prostaglandin E2 (PGE2), and between cartilage relaxation time and CT and PGE2. SVF treatment was the only limit on the deleterious OA effect on cartilage viscoelastic properties. This work provides indications to future studies aiming to highlight these and other relationships and focusing on advanced regeneration targets.
The damping system ensured by the osteochondral (OC) unit is essential to deploy the forces generated within load-bearing joints during locomotion, allowing furthermore low-friction sliding motion ...between bone segments. The OC unit is a multi-layer structure including articular cartilage, as well as subchondral and trabecular bone. The interplay between the OC tissues is essential in maintaining the joint functionality; altered loading patterns can trigger biological processes that could lead to degenerative joint diseases like osteoarthritis. Currently, no effective treatments are available to avoid degeneration beyond tissues' recovery capabilities. A thorough comprehension on the mechanical behaviour of the OC unit is essential to (i) soundly elucidate its overall response to intra-articular loads for developing diagnostic tools capable of detecting non-physiological strain levels, (ii) properly evaluate the efficacy of innovative treatments in restoring physiological strain levels, and (iii) optimize regenerative medicine approaches as potential and less-invasive alternatives to arthroplasty when irreversible damage has occurred. Therefore, the leading aim of this review was to provide an overview of the state-of-the-art-up to 2022-about the mechanical behaviour of the OC unit. A systematic search is performed, according to PRISMA standards, by focusing on studies that experimentally assess the human lower-limb joints' OC tissues. A multi-criteria decision-making method is proposed to quantitatively evaluate eligible studies, in order to highlight only the insights retrieved through sound and robust approaches. This review revealed that studies on human lower limbs are focusing on the knee and articular cartilage, while hip and trabecular bone studies are declining, and the ankle and subchondral bone are poorly investigated. Compression and indentation are the most common experimental techniques studying the mechanical behaviour of the OC tissues, with indentation also being able to provide information at the micro- and nanoscales. While a certain comparability among studies was highlighted, none of the identified testing protocols are currently recognised as standard for any of the OC tissues. The fibril-network-reinforced poro-viscoelastic constitutive model has become common for describing the response of the articular cartilage, while the models describing the mechanical behaviour of mineralised tissues are usually simpler (i.e., linear elastic, elasto-plastic). Most advanced studies have tested and modelled multiple tissues of the same OC unit but have done so individually rather than through integrated approaches. Therefore, efforts should be made in simultaneously evaluating the comprehensive response of the OC unit to intra-articular loads and the interplay between the OC tissues. In this regard, a multidisciplinary approach combining complementary techniques, e.g., full-field imaging, mechanical testing, and computational approaches, should be implemented and validated. Furthermore, the next challenge entails transferring this assessment to a non-invasive approach, allowing its application in vivo, in order to increase its diagnostic and prognostic potential.
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•Electrospun bundles with myotendinous-inspired Polyurethane-Nylon 6.6 junctions are produced.•Bundles successfully show a similar morphology to the natural counterpart.•MicroCT ...investigation confirmed the conical and flat morphology of the junctions.•Mechanical tensile tests highlighted different behaviors of bundles depending on the junction used.•Cyclic tests revealed mechanical stability of junctions and their ability to dampen nylon 6.6 hardening over time.
Soft robotics aims to replicate the structure and mechanics of skeletal muscles. The challenge lies in seamlessly integrating these muscle-inspired soft actuators with the joints they intend to actuate, resembling the natural connection between muscles and tendons (i.e., myotendinous junction). This study addresses this issue by producing electrospun bundles of aligned nanofibers using a thermoplastic polyurethane, mimicking the muscle fascicle, and nylon 6.6 for the tendon one. A novel method was developed to create electrospun bi-material bundles with two different types of myotendinous-inspired junctions, called flat and conical. Scanning electron microscopy and microtomography analyses confirmed that conical junctions mimicked natural myotendinous structures better than flat ones. Tensile mechanical tests demonstrated that bi-material junctions reached stress at failure comparable to polyurethane bundles (11 ± 2 MPa), with the conical junction showing stiffness (0.13 ± 0.02 N/mm) and net elastic modulus (153 ± 10 MPa) values closer to the natural myotendinous ones. Cyclic tests verified the mechanical stability of junctions and their ability to dampen nylon 6.6 hardening over time. Moreover, all bundles withstood cyclic loading without breaking. These findings suggest the potential of biomimetic electrospun junctions for applications in soft robotics, marking a significant step toward advancing this field.
Purpose
The aim of the present study was to trace knee position at the time of bone bruise (BB) and investigate how much this position departed from the knee biomechanics of an in vivo ...flexion–extension.
Methods
From an original cohort of 62 patients, seven (11%) presented bicompartmental edemas and were included in the study. 3D models of bones and BB were obtained from MRI. Matching bone edemas, a reconstruction of the knee at the moment of BB was obtained. For the same patients, knee kinematics of a squat was calculated using dynamic Roentgen sterephotogrammetric analysis (RSA). Data describing knee position at the moment of BB were compared to kinematics of the same knee extrapolated from RSA system.
Results
Knee positions at the moment of BB was significantly different from the kinematics of the squat. In particular, all the patients’ positions were out of squat range for both anterior and proximal tibial translation, varus–valgus rotation (five in valgus and two in varus), tibial internal–external rotation (all but one, five externally and one internally). A direct comparison at same flexion angle between knee at the moment of BB (average 46.1° ± 3.8°) and knee during squat confirmed that tibia in the former was significantly more anterior (
p
< 0.0001), more externally rotated (6.1 ± 3.7°,
p
= 0.04), and valgus (4.1 ± 2.4°,
p
= 0.03).
Conclusion
Knee position at the moment of Bone bruise position was out of physiological in-vivo knee range of motion and could reflect a locked anterior subluxation occurring in the late phase of ACL injury rather than the mechanism leading to ligament failure.
Level of evidence
Level IV
Cranial reconstructions are essential for restoring both function and aesthetics in patients with craniofacial deformities or traumatic injuries. Titanium prostheses have gained popularity due to ...their biocompatibility, strength, and corrosion resistance. The use of Superplastic Forming (SPF) and Single Point Incremental Forming (SPIF) techniques to create titanium prostheses, specifically designed for cranial reconstructions was investigated in an ovine model through microtomographic and histomorphometric analyses. The results obtained from the explanted specimens revealed significant variations in bone volume, trabecular thickness, spacing, and number across different regions of interest (VOIs or ROIs). Those regions next to the center of the cranial defect exhibited the most immature bone, characterized by higher porosity, decreased trabecular thickness, and wider trabecular spacing. Dynamic histomorphometry demonstrated differences in the mineralizing surface to bone surface ratio (MS/BS) and mineral apposition rate (MAR) depending on the timing of fluorochrome administration. A layer of connective tissue separated the prosthesis and the bone tissue. Overall, the study provided validation for the use of cranial prostheses made using SPF and SPIF techniques, offering insights into the processes of bone formation and remodeling in the implanted ovine model.
Many biomaterials’ surfaces exhibit directional properties, i.e., possess spatial anisotropy on a range of spatial scales spanning from the domain of the naked eye to the sub-micrometer level. ...Spatial anisotropy of surface can influence the mechanical, physicochemical, and morphological characteristics of the biomaterial, thus affecting its functional behavior in relation, for example, to the host tissue response in regenerative processes, or to the efficacy of spatially organized surface patterns in avoiding bacterial attachment. Despite the importance of the availability of quantitative data, a comprehensive characterization of anisotropic topographies is generally a hard task due to the proliferation of parameters and inherent formal complications. This fact has led so far to excessive simplification that has often prevented researchers from having comparable results. In an attempt to overcome these issues, in this work a systematic and multiscale approach to spatial anisotropy is adopted, based on the determination of only two statistical parameters of surface, namely the texture aspect ratio Str and the roughness exponent H, extracted from atomic force microscopy images of the surface. The validity on this approach is tested on four commercially available implant materials, namely titanium alloy, polyethylene, polyetheretherketone and polyurethane, characterized by textured surfaces obtained after different machining. It is found that the “two parameters” approach is effective in describing the anisotropy changes on surfaces with complex morphology, providing a simple quantitative route for characterization and design of natural and artificial textured surfaces at spatial scales relevant to a wide range of bio-oriented applications.
In the development of bone graft substitutes, a fundamental step is the use of scaffolds with adequate composition and architecture capable of providing support in regenerative processes both on the ...tissue scale, where adequate resistance to mechanical stress is required, as well as at the cellular level where compliant chemical-physical and mechanical properties can promote cellular activity. In this study, based on a previous optimization study of this group, the potential of a three-dimensional construct based on polycaprolactone (PCL) and a novel biocompatible Mg- and Sr-containing glass named BGMS10 was explored. Fourier-transform infrared spectroscopy and scanning electron microscopy showed the inclusion of BGMS10 in the scaffold structure. Mesenchymal stem cells cultured on both PCL and PCL-BGMS10 showed similar tendencies in terms of osteogenic differentiation; however, no significant differences were found between the two scaffold types. This circumstance can be explained via X-ray microtomography and atomic force microscopy analyses, which correlated the spatial distribution of the BGMS10 within the bulk with the elastic properties and topography at the cell scale. In conclusion, our study highlights the importance of multidisciplinary approaches to understand the relationship between design parameters, material properties, and cellular response in polymer composites, which is crucial for the development and design of scaffolds for bone regeneration.
Polycaprolactone (PCL) is widely used in additive manufacturing for the construction of scaffolds for tissue engineering because of its good bioresorbability, biocompatibility, and processability. ...Nevertheless, its use is limited by its inadequate mechanical support, slow degradation rate and the lack of bioactivity and ability to induce cell adhesion and, thus, bone tissue regeneration. In this study, we fabricated 3D PCL scaffolds reinforced with a novel Mg-doped bioactive glass (Mg-BG) characterized by good mechanical properties and biological reactivity. An optimization of the printing parameters and scaffold fabrication was performed; furthermore, an extensive microtopography characterization by scanning electron microscopy and atomic force microscopy was carried out. Nano-indentation tests accounted for the mechanical properties of the scaffolds, whereas SBF tests and cytotoxicity tests using human bone-marrow-derived mesenchymal stem cells (BM-MSCs) were performed to evaluate the bioactivity and in vitro viability. Our results showed that a 50/50 wt% of the polymer-to-glass ratio provides scaffolds with a dense and homogeneous distribution of Mg-BG particles at the surface and roughness twice that of pure PCL scaffolds. Compared to pure PCL (hardness H = 35 ± 2 MPa and Young’s elastic modulus E = 0.80 ± 0.05 GPa), the 50/50 wt% formulation showed H = 52 ± 11 MPa and E = 2.0 ± 0.2 GPa, hence, it was close to those of trabecular bone. The high level of biocompatibility, bioactivity, and cell adhesion encourages the use of the composite PCL/Mg-BG scaffolds in promoting cell viability and supporting mechanical loading in the host trabecular bone.
Poly-ε-caprolactone (PCL) has been widely used in additive manufacturing for the construction of scaffolds for bone tissue engineering. However, its use is limited by its lack of bioactivity and ...inability to induce cell adhesion, hence limiting bone tissue regeneration. Biomimicry is strongly influenced by the dynamics of cell-substrate interaction. Thus, characterizing scaffolds at the cell scale could help to better understand the relationship between surface mechanics and biological response. We conducted atomic force microscopy-based nanoindentation on 3D-printed PCL fibers of ~300 µm thickness and mapped the near-surface Young's modulus at loading forces below 50 nN. In this non-disruptive regime, force mapping did not show clear patterns in the spatial distribution of moduli or a relationship with the topographic asperities within a given region. Remarkably, we found that the average modulus increased linearly with the logarithm of the strain rate. Finally, a dependence of the moduli on the history of nanoindentation was demonstrated on locations of repeated nanoindentations, likely due to creep phenomena capable of hindering viscoelasticity. Our findings can contribute to the rational design of scaffolds for bone regeneration that are capable of inducing cell adhesion and proliferation. The methodologies described are potentially applicable to various tissue-engineered biopolymers.
Background:
The role of meniscal lesions and repair in combination with anterior cruciate ligament (ACL) injury and reconstruction has not been extensively investigated in vivo and under ...weightbearing conditions.
Purpose:
The purposes of this study were to (1) compare the in vivo knee kinematics between patients with ACL tear and those with combined ACL and medial meniscal tears and (2) investigate kinematic differences between isolated ACL reconstruction and ACL reconstruction plus medial meniscal repair (MR). It was hypothesized that concomitant posterior horn medial meniscal tear and ACL deficiency would affect knee internal-external rotation and anterior-posterior translation but MR would restore these parameters.
Study Design:
Controlled laboratory study.
Methods:
Nineteen patients who underwent ACL reconstruction were included: 10 had intact menisci (IM group) and 9 had a medial meniscal injury that was repaired during ACL reconstruction using an all-inside technique (MR group). Preoperatively and 18 months postoperatively, active knee kinematics under weightbearing conditions was evaluated during a single-leg squat using a dynamic biplane x-ray imaging system. The general linear model was used to investigate the differences between group (IM vs MR) and time (preoperative vs follow-up) and their interactions.
Results:
Tibial internal rotation was higher in the MR group than the IM group both before and after surgery (P = .007). Knee valgus rotation was higher in the MR group preoperatively (P < .001), while no differences were found postoperatively because of an increase of valgus rotation in the IM group, which was significant in the descendant phase (P < .001). Preoperatively, the IM group showed a more medial tibial translation compared with the MR group in the descendant phase (P = .006).
Conclusion:
When performing a single-leg squat, patients with ACL-deficient knees and a medial meniscal tear demonstrated a more valgus rotation, tibial internal rotation, and lateral tibial translation versus those with intact menisci. After ACL reconstruction and MR, these patients demonstrated significantly higher tibial internal rotation when compared with patients who underwent isolated ACL reconstruction.
Clinical Relevance:
Surgeons should be aware that MR does not fully restore knee kinematics in vivo and under weightbearing conditions in the context of ACL reconstruction.
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