Near-Surface Nanomechanics of Medical-Grade PEEK Measured by Atomic Force Microscopy.

Detecting subtle changes of surface stiffness at spatial scales and forces relevant to biological processes is crucial for the characterization of biopolymer systems in view of chemical and/or physical surface modification aimed at improving bioactivity and/or mechanical strength. Here, a standard atomic force microscopy setup is operated in nanoindentation mode to quantitatively mapping the near-surface elasticity of semicrystalline polyether ether ketone (PEEK) at room temperature. Remarkably, two localized distributions of moduli at about 0.6 and 0.9 GPa are observed below the plastic threshold of the polymer, at indentation loads in the range of 120-450 nN. This finding is ascribed to the localization of the amorphous and crystalline phases on the free surface of the polymer, detected at an unprecedented level of detail. Our study provides insights to quantitatively characterize complex biopolymer systems on the nanoscale and to guide the optimal design of micro- and nanostructures for advanced biomedical applications.

Knee Joint Contact Forces during High-Risk Dynamic Tasks: 90° Change of Direction and Deceleration Movements.

Pivoting sports expose athletes to a high risk of knee injuries, mainly due to mechanical overloading of the joint which shatters overall tissue integrity. The present study explored the magnitude of tibiofemoral contact forces (TFCF) in high-risk dynamic tasks. A novel musculoskeletal model with modifiable frontal plane knee alignment was developed to estimate the total, medial, and lateral TFCF developed during vigorous activities. Thirty-one competitive soccer players performing deceleration and 90° sidestepping tasks were assessed via 3D motion analysis by using a marker-based optoelectronic system and TFCF were assessed via OpenSim software. Statistical parametric mapping was used to investigate the effect of frontal plane alignment, compartment laterality, and varus-valgus genu on TFCF. Further, in consideration of specific risk factors, sex influence was also assessed. A strong correlation (R = 0.71 ÷ 0.98, p < 0.001) was found between modification of compartmental forces and changes in frontal plane alignment. Medial and lateral TFCF were similar throughout most of the tasks with the exception of the initial phase, where the lateral compartment had to withstand to higher loadings (1.5 ÷ 3 BW higher, p = 0.010). Significant sex differences emerged in the late phase of the deceleration task. A comprehensive view of factors influencing the mediolateral distribution of TFCF would benefit knee injury prevention and rehabilitation in sport activities.

Fast-track protocols for patients undergoing spine surgery: a systematic review.

BACKGROUND CONTEXT: Fast-track is an evidence-based multidisciplinary strategy for pre-, intra-, and postoperative management of patients during major surgery. To date, fast-track has not been recognized or accepted in all surgical areas, particularly in orthopedic spine surgery where it still represents a relatively new paradigm. PURPOSE: The aim of this review was provided an evidenced-based assessment of specific interventions, measurement, and associated outcomes linked to enhanced recovery pathways in spine surgery field. METHODS: We conducted a systematic review in three databases from February 2012 to August 2022 to assess the pre-, intra-, and postoperative key elements and the clinical evidence of fast-track protocols as well as specific interventions and associated outcomes, in patients undergoing to spine surgery. RESULTS: We included 57 full-text articles of which most were retrospective. Most common fast-track elements included patient's education, multimodal analgesia, thrombo- and antibiotic prophylaxis, tranexamic acid use, urinary catheter and drainage removal within 24 hours after surgery, and early mobilization and nutrition. All studies demonstrated that these interventions were able to reduce patients' length of stay (LOS) and opioid use. Comparative studies between fast-track and non-fast-track protocols also showed improved pain scores without increasing complication or readmission rates, thus improving patient's satisfaction and functional recovery. CONCLUSIONS: According to the review results, fast-track seems to be a successful tool to reduce LOS, accelerate return of function, minimize postoperative pain, and save costs in spine surgery. However, current studies are mainly on degenerative spine diseases and largely restricted to retrospective studies with non-randomized data, thus multicenter randomized trials comparing fast-track outcomes and implementation are mandatory to confirm its benefit in spine surgery.

Nanomechanical Mapping of Hard Tissues by Atomic Force Microscopy: An Application to Cortical Bone.

Force mapping of biological tissues via atomic force microscopy (AFM) probes the mechanical properties of samples within a given topography, revealing the interplay between tissue organization and nanometer-level composition. Despite considerable attention to soft biological samples, constructing elasticity maps on hard tissues is not routine for standard AFM equipment due to the difficulty of interpreting nanoindentation data in light of the available models of surface deformation. To tackle this issue, we proposed a protocol to construct elasticity maps of surfaces up to several GPa in moduli by AFM nanoindentation using standard experimental conditions (air operation, nanometrically sharp spherical tips, and cantilever stiffness below 30 N/m). We showed how to process both elastic and inelastic sample deformations simultaneously and independently and quantify the degree of elasticity of the sample to decide which regime is more suitable for moduli calculation. Afterwards, we used the frequency distributions of Young's moduli to quantitatively assess differences between sample regions different for structure and composition, and to evaluate the presence of mechanical inhomogeneities. We tested our method on histological sections of sheep cortical bone, measuring the mechanical response of different osseous districts, and mapped the surface down to the single collagen fibril level.

Speculation on the pathophysiology of musculoskeletal injury with COVID-19 infection.

Coronavirus disease 2019 (COVID-19) primarily affects the respiratory tract, but also many other organs and tissues, leading to different pathological pictures, such as those of the musculoskeletal tissues. The present study should be considered as a speculation on the relationship between COVID-19 infection and some frequent musculoskeletal pathologies, in particular sarcopenia, bone loss/osteoporosis (OP) and fracture risk and osteoarthritis (OA), to hypothesize how the virus acts on these pathologies and consequently on the tissue regeneration/healing potential. The study focuses in particular on the modalities of interaction of COVID-19 with Angiotensin-Converting Enzyme 2 (ACE2) and on the "cytokine storm." Knowing the effects of COVID-19 on musculoskeletal tissues could be important also to understand if tissue regenerative/reparative capacity is compromised, especially in elderly and frail patients. We speculate that ACE2 and serine proteases together with an intense inflammation, immobilization and malnutrition could be the responsible for muscle weakness, altered bone remodeling, increase in bone fracture risk and inflammatory joint pathologies. Future preclinical and clinical studies may focus on the regenerative/reparative properties of the musculoskeletal tissues after COVID-19 infection, toward a personalized treatment usually based on scaffolds, cells, and growth factors.

Key Components, Current Practice and Clinical Outcomes of ERAS Programs in Patients Undergoing Orthopedic Surgery: A Systematic Review.

Enhanced recovery after surgery (ERAS) protocols have led to improvements in outcomes in several surgical fields, through multimodal optimization of patient pathways, reductions in complications, improved patient experiences and reductions in the length of stay. However, their use has not been uniformly recognized in all orthopedic fields, and there is still no consensus on the best implementation process. Here, we evaluated pre-, peri-, and post-operative key elements and clinical evidence of ERAS protocols, measurements, and associated outcomes in patients undergoing different orthopedic surgical procedures. A systematic literature search on PubMed, Scopus, and Web of Science Core Collection databases was conducted to identify clinical studies, from 2012 to 2022. Out of the 1154 studies retrieved, 174 (25 on spine surgery, 4 on thorax surgery, 2 on elbow surgery and 143 on hip and/or knee surgery) were considered eligible for this review. Results showed that ERAS protocols improve the recovery from orthopedic surgery, decreasing the length of hospital stays (LOS) and the readmission rates. Comparative studies between ERAS and non-ERAS protocols also showed improvement in patient pain scores, satisfaction, and range of motion. Although ERAS protocols in orthopedic surgery are safe and effective, future studies focusing on specific ERAS elements, in particular for elbow, thorax and spine, are mandatory to optimize the protocols.

Determination of the Spatial Anisotropy of the Surface MicroStructures of Different Implant Materials: An Atomic Force Microscopy Study.

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.

The Impact of Frailty on Spine Surgery: Systematic Review on 10 years Clinical Studies.

Frailty is a condition characterized by a high vulnerability to low-power stressor. Frailty increases with age and is associated with higher complications and mortality. Several indexes have been used to quantify frailty. Spine diseases, both degenerative and oncologic, frequently require surgery which is related to complications and mortality. Aim of the present systematic review was to collect the most frequently used frailty indexes in clinics to predict surgical outcomes in patients affected by spine diseases, taking into account gender differences. Three databases were employed, and 29 retrospective clinical studies were included in this systematic review. The identified spine pathologies were primary and metastatic spine tumors, adult spine deformity (ASD), degenerative spine disease (DSD), cervical deformity (CD) and other pathologies that affected lumbar spine or multiple spine levels. Eleven indexes were identified: modified Frailty Index (mFI), Adult spinal deformity frailty index (ASD-FI), mFI-5, Metastatic Spinal Tumor Frailty Index (MSTFI), Fried criteria, Cervical deformity frailty index (CD-FI), Spinal tumor frailty index (STFI), Frailty Phenotype criteria (FP), Frailty Index (FI), FRAIL scale and Modified CD-FI (mCD-FI). All these indexes correlated well with minor and major postoperative complications, mortality and length of stay in hospital. Results on gender differences and frailty are still conflicting, although few studies show that women are more likely to develop frailty and more complications in the post-operative period than men. This systematic review could help the surgeon in the adoption of frailty indexes, before the operation, and in preventing complications in frail patients.

Nano-Based Biomaterials as Drug Delivery Systems Against Osteoporosis: A Systematic Review of Preclinical and Clinical Evidence.

Osteoporosis (OP) is one of the most significant causes of morbidity, particularly in post-menopausal women and older men. Despite its remarkable occurrence, the search for an effective treatment is still an open challenge. Here, we systematically reviewed the preclinical and clinical progress in the development of nano-based materials as drug delivery systems against OP, considering the effects on bone healing and regeneration, the more promising composition and manufacturing methods, and the more hopeful drugs and delivery methods. The results showed that almost all the innovative nano-based delivery systems developed in the last ten years have been assessed by preclinical investigations and are still in the preliminary/early research stages. Our search strategy retrieved only one non-randomized controlled trial (RCT) on oligosaccharide nanomedicine of alginate sodium used for degenerative lumbar diseases in OP patients. Further investigations are mandatory for assessing the clinical translation and commercial purposes of these materials. To date, the main limits for the clinical translation of nano-based materials as drug delivery systems against OP are probably due to the low reproducibility of the manufacturing processes, whose specificity and complexity relies on an adequate chemical, structural, and biomechanical characterization, as the necessary prerequisite before assessing the efficacy of a given treatment or process. Finally, an unsatisfactory drug-loading capacity, an uncontrollable release kinetic, and a low delivery efficiency also limit the clinical application.

How preconditioning and pretensioning of grafts used in ACLigaments surgical reconstruction are influenced by their mechanical time-dependent characteristics: Can we optimize their initial loading state?

PURPOSE: Consensus about a pre-implant preparation protocol adaptable to any graft used in Anterior Cruciate Ligament reconstruction is still lacking. In fact, there is not agreement on reliable metrics that consider both specific graft dimensional characteristics, such as its diameter, and the inherent properties of its constitutive material, i.e. ligaments or tendons. Aim of the present study was to investigate and propose the applied engineering stress as a possible metrics. METHODS: Preconditioning and pretensioning protocol involved groups of grafts with different section (10 or 32 mm2) and materials (i.e. human patellar and hamstring tendons, and synthetic grafts). A 140 N load was applied to the grafts and maintained for 100 s. Initial stress and following stress-relaxation (a mechanical characteristic that can be related to knee laxity) were specifically analysed. FINDINGS: Initial stress, ranging between 4 and 12 MPa, was affected primarily by the graft cross-section area and secondarily by the choice of the graft material. In terms of loss of the initial stress, stress-relaxation behaviour varied instead on a narrower range, namely 13-17%. INTERPRETATION: Engineering stress can be identified as the correct metrics to optimize the initial state of each graft to avoid excessive stiffness, laxity or fatigue rupture phenomena.

Evidence from systematic reviews on photobiomodulation of human bone and stromal cells: Where do we stand?

This study summarizes the available evidence from systematic reviews on the in vitro effects of photobiomodulation on the proliferation and differentiation of human bone and stromal cells by appraising their methodological quality. Improvements for future studies are also highlighted, with particular emphasis on in vitro protocols and cell-related characteristics. Six reviews using explicit eligibility criteria and methods selected in order to minimize bias were included. There was no compelling evidence on the cellular mechanisms of action or treatment parameters of photobiomodulation; compliance with quality assessment was poor. A rigorous description of laser parameters (wavelength, power, beam spot size, power density, energy density, repetition rate, pulse duration or duty cycle, exposure duration, frequency of treatments, and total radiant energy), exposure conditions (methods to ensure a uniform irradiation and to avoid cross-irradiation, laser-cell culture surface distance, lid presence during irradiation) and cell-related characteristics (cell type or line, isolation and culture conditions, donor-related factors where applicable, tissue source, cell phenotype, cell density, number of cell passages in culture) should be included among eligibility criteria for study inclusion. These methodological improvements will maximize the contribution of in vitro studies on the effects of photobiomodulation on human bone and stromal cells to evidence-based translational research.

Biosensors for real-time monitoring of physiological processes in the musculoskeletal system: A systematic review.

Biosensors are composed of (bio)receptors, transducers, and detection systems and are able to convert the biological stimulus into a measurable signal. This systematic review evaluates the current state of the art of innovation and research in this field, identifying the biosensors that in vitro monitor the musculoskeletal system cellular processes. Two databases found 20 in vitro studies, from January 1, 2008 to December 31, 2017, dealing with musculoskeletal system cells. The biosensors were divided into two groups based on the transduction mechanism: optical or electrochemical. The first group evaluated osteoblasts or mesenchymal stem cell (MSC) biocompatibility, viability, differentiation, alkaline phosphatase, enzyme, and protein detection. The second group detected cell impedance, ATP release, and superoxide concentration in tenocytes, osteoblasts, MSCs, and myoblasts. This review highlighted that the in vitro scenario is still at an early phase and limited for what concerns both the type of bioanalyte and for the type of system detector used.

Nanoindentation: An advanced procedure to investigate osteochondral engineered tissues.

Osteochondral scaffolds are emerging as a promising alternative for articular cartilage regeneration, although with still controversial results. In particular, the restoration of the osteochondral interface remains an open challenge. The current available investigative procedures are not optimal to quantify the properties of this region, neither to evaluate the quality of the regenerated tissue with respect to the physiological one. This study investigates an advanced procedure able to quantitatively evaluate the mechanical gradient between stiff and compliant tissues, such as in the osteochondral region where the interface between hyaline and calcified cartilage (tidemark) plays an integral role in transferring articular loads from the compliant articular surface to the stiffer underlying bone. A series of nanoindentation line scans was performed along the tidemark - starting from hyaline and expanding across calcified cartilage - on histological sections derived from sheep osteochondral tissue regenerated by a three-layered biomimetic scaffold, as well as to the adjacent healthy tissue for comparative purposes. After an accurate assessment of the indentation parameters, a sigmoid curve-fit function was applied on the reduced modulus profiles to extract gap, width and regularity of the mechanical transition. The designed procedure succeeded in quantitatively assessing the transition between compliant and stiff regions, limiting experimental issues that generally affect the reliability of the indentation mechanical data, such as apex-blunt indenter tip effect, surface roughness, and influence of the substrate. Among the evaluated parameters, the mechanical gap highlighted the main difference between native and regenerated tissues. Thanks to the information retrievable through this procedure, this load transmission area can be further investigated, providing data to tailor osteochondral engineered tissues in the future.

Osteogenic Differentiation of hDPSCs on Biogenic Bone Apatite Thin Films.

A previous study reported the structural characterization of biogenic apatite (BAp) thin films realized by a pulsed electron deposition system by ablation of deproteinized bovine bone. Thin films annealed at 400°C exhibited composition and crystallinity degree very close to those of biogenic apatite; this affinity is crucial for obtaining faster osseointegration compared to conventional, thick hydroxyapatite (HA) coatings, for both orthopedics and dentistry. Here, we investigated the adhesion, proliferation, and osteogenic differentiation of human dental pulp stem cells (hDPCS) on as-deposited and heat-treated BAp and stoichiometric HA. First, we showed that heat-treated BAp films can significantly promote hDPSC adhesion and proliferation. Moreover, hDPSCs, while initially maintaining the typical fibroblast-like morphology and stemness surface markers, later started expressing osteogenic markers such as Runx-2 and OSX. Noteworthy, when cultured in an osteogenic medium on annealed BAp films, hDPSCs were also able to reach a more mature and terminal commitment, with respect to HA and as-deposited films. Our findings suggest that annealed BAp films not only preserve the typical biological properties of stemness of, hDPSCs but also improve their ability of osteogenic commitment.

Corrigendum to "Osteogenic Differentiation of hDPSCs on Biogenic Bone Apatite Thin Films".

[This corrects the article DOI: 10.1155/2017/3579283.].

Changes in the orientation of knee functional flexion axis during passive flexion and extension movements in navigated total knee arthroplasty.

PURPOSE: Recently, the functional flexion axis has been considered to provide a proper rotational alignment of the femoral component in total knee arthroplasty. Several factors could influence the identification of the functional flexion axis. The purpose of this study was to analyse the estimation of the functional flexion axis by separately focusing on passive flexion and extension movements and specifically assessing its orientation compared to the transepicondylar axis, in both the axial plane and the frontal plane. METHODS: Anatomical and kinematic acquisitions were performed using a commercial navigation system on 79 patients undergoing total knee arthroplasty with cruciate substituting prosthesis design. The functional flexion axis was estimated from passive movements, between 0° and 120° of flexion and back. Intra-observer agreement and reliability, internal-external rotation and the angle with the surgical transepicondylar axis, in axial and frontal planes, were separately analysed for flexion and extension, in pre- and post-implant conditions. RESULTS: The analysis of reliability and agreement showed good results. The identification of the functional flexion axis showed statistically significant differences both in relation to flexion and extension and to pre- and post-implant conditions, both in frontal plane and in axial plane. The analysis of internal-external rotation confirmed these differences in kinematics (p < 0.05, between 25° and 35° of flexion). CONCLUSIONS: The identification of the functional flexion axis changed in relation to passive flexion and extension movements, above all in frontal plane, while it resulted more stable and reliable in axial plane. These findings supported the possible clinical application of the functional flexion axis in the surgical practice by implementing navigated procedures. However, further analyses are required to better understand the factors affecting the identification of the functional flexion axis. LEVEL OF EVIDENCE: IV.

Comparison of three formal methods used to estimate the functional axis of rotation: an extensive in-vivo analysis performed on the knee joint.

Estimating the main axis of rotation (AoR) of a human joint represents an important issue in biomechanics. This study compared three formal methods used to estimate functional AoR, namely a cylindrical fitting method, a mean helical axis transformation, and a symmetrical axis approach. These methods were tested on 106 subjects undergoing navigated total knee arthroplasty. AoR orientation in 3D and in the frontal and coronal planes provided by each method was compared to the transepicondylar axis direction. Although all the methods resulted effective, significant differences were identified among them, relatively to the orientation in 3D and in the frontal plane projection. This was probably due to the presence of secondary rotations during the first degrees of knee flexion.

Application of magnetic rods for fixation in orthopedic treatments.

Achieving an efficient fixation for complicated fractures and scaffold application treatments is a challenging surgery problem. Although many fixation approaches have been advanced and actively pursued, the optimal solution for long bone defects has not yet been defined. This paper promotes an innovative fixation method based on application of magnetic forces. The efficiency of this approach was investigated on the basis of finite element modeling for scaffold application and analytical calculations for diaphyseal fractures. Three different configurations have been analyzed including combinations of small cylindrical permanent magnets or stainless steel rods, inserted rigidly in the bone intramedullary canals and in the scaffold. It was shown that attractive forces as high as 75 N can be achieved. While these forces do not reach the strength of mechanical forces in traditional fixators, the employment of magnetic rods is expected to be beneficial by reducing considerably the interface micromotions. It can additionally support magneto-mechanical stimulations as well as enabling a magnetically assisted targeted delivery of drugs and other bio-agents.

Can rotatory knee laxity be predicted in isolated anterior cruciate ligament surgery?

PURPOSE: Despite the overall success of the surgical anterior cruciate ligament (ACL) reconstruction, some patients still present with instability symptoms even after the surgery, mainly due to the presence of associated lesions. At present, the pivot shift test has been reported to be the benchmark to assess rotatory knee laxity. The purpose of this study was to quantitatively evaluate rotatory knee laxity at time-zero in order to determine whether detected post-reconstruction laxity was predictable by its value measured before the reconstruction, which was hypothized to be influenced by the presence of associated lesions. METHODS: Rotatory knee laxity was retrospectively analysed in 42 patients, including two different ACL reconstructions. The maximal anterior displacement and the absolute value of the posterior acceleration reached during the reduction of the tibial lateral compartment were intra-operatively acquired by using a navigation system and identified as discriminating parameters. For each parameter, statistical linear regression analysis (line slope and intercept) was performed between pre- and post-reconstruction values. RESULTS: No statistically significant influence of the initial posterior acceleration on the post-reconstruction outcome was found (line slope, p > 0.05), although a statistically significant line intercept was indeed identified (p < 0.001). A statistically significant influence on the surgery outcome was instead found for the initial value of the anterior tibial displacement (line slope = 0.39, p = 0.004), meaning that, on average, about 40 % of the post-reconstruction lateral compartment displacement could be explained by the corresponding pre-reconstruction value. Both of these findings highlighted the importance of intra-operative quantification of rotatory knee laxity to identify correct indications for the surgery. CONCLUSIONS: This study provided important implications for the future possibility of defining a quantifying tool able to assess rotatory knee laxity during ACL reconstruction. This could allow detection of additional injuries to secondary restraints by easily performing rotatory knee laxity tests, which in turn could reduce post-surgical recurrence of knee instability.

Analysis of knee functional flexion axis in navigated TKA: identification and repeatability before and after implant positioning.

PURPOSE: Providing correct rotational alignment of femoral component in total knee arthroplasty (TKA) is mandatory to achieve correct kinematics, good ligament balance and patellar tracking. The purpose of this study was to evaluate potential clinical applications of functional flexion axis (FFA) by analysing the differences between pre- and post-implant placement. This evaluation was supported by the analysis of repeatability, assessing the robustness of the proposed method. METHODS: Anatomical acquisitions and passive kinematics were acquired on 87 patients undergoing TKA using a commercial navigation system. Knee FFA was estimated, before and after implant positioning, from three flexion-extension movements between 0 and 120°. The angle between FFA and transepicondylar axis was analysed in frontal and axial planes. Repeatability coefficient and intraclass correlation coefficient (ICC) were used to analyse the reliability and the agreement in identifying the axis. RESULTS: The analysed angle presented differences between pre- and post-operative conditions only in the frontal plane (from -8.3 ± 5.5° to -2.8 ± 5.3°) (p < 0.0001). There was good intraobserver reliability and agreement. Repeatability coefficient ranged between 4.4° (3.7-4.9°) and 3.4° (2.9-3.8°), the ICC between 0.87 (0.83-0.91) and 0.93 (0.90-0.95) and the standard deviation ranged between 1.3 and 1.0°. CONCLUSIONS: The present study demonstrated that TKA affected the estimation of FFA only in the frontal plane. This method reported good repeatability, demonstrating its usefulness for clinical purposes particularly to evaluate rotational positioning of the femoral component in the axial plane. LEVEL OF EVIDENCE: Case series, Level IV.