In vivo validation of highly customized cranial Ti-6AL-4V ELI prostheses fabricated through incremental forming and superplastic forming: an ovine model study.

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.

Ionized jet deposition of silver nanostructured coatings: Assessment of chemico-physical and biological behavior for application in orthopedics.

Infection is one of the main issues connected to implantation of biomedical devices and represents a very difficult issue to tackle, for clinicians and for patients. This study aimed at tackling infection through antibacterial nanostructured silver coatings manufactured by Ionized Jet Deposition (IJD) for application as new and advanced coating systems for medical devices. Films composition and morphology depending on deposition parameters were investigated and their performances evaluated by correlating these properties with the antibacterial and antibiofilm efficacy of the coatings, against Escherichia coli and Staphylococcus aureus strains and with their cytotoxicity towards human cell line fibroblasts. The biocompatibility of the coatings, the nanotoxicity, and the safety of the proposed approach were evaluated, for the first time, in vitro and in vivo by rat subcutaneous implant models. Different deposition times, corresponding to different thicknesses, were selected and compared. All silver coatings exhibited a highly homogeneous surface composed of nanosized spherical aggregates. All coatings having a thickness of 50 nm and above showed high antibacterial efficacy, while none of the tested options caused cytotoxicity when tested in vitro. Indeed, silver films impacted on bacterial strains viability and capability to adhere to the substrate, in a thickness-dependent manner. The nanostructure obtained by IJD permitted to mitigate the toxicity of silver, conferring strong antibacterial and anti-adhesive features, without affecting the coatings biocompatibility. At the explant, the coatings were still present although they showed signs of progressive dissolution, compatible with the release of silver, but no cracking, delamination or in vivo toxicity was observed.

3D visualization of the human anterior cruciate ligament combining micro-CT and histological analysis.

PURPOSE: The study aimed to obtain a comprehensive 3D visualization of knee specimens, including the cruciate ligaments and corresponding femoral and tibial bone insertions using a non-destructive micro-CT method. METHODS: Knee specimens were fixed in anatomical positions and chemically dehydrated before being scanned using micro-CT with a voxel size of 17.5 µm. RGBA (red, green, blue, alpha) transfer functions were applied to virtually colorize each structure. Following micro-CT scanning, the samples were rehydrated, decalcified, and trimmed based on micro-CT 3D reconstructions as references. Histological evaluations were performed on the trimmed samples. Histological and micro-CT images were registered to morphologically and densitometrically assess the 4-layer insertion of the ACL into the bone. RESULTS: The output of the micro-CT images of the knee in extension and flexion allowed a clear differentiation of the morphologies of both soft and hard tissues, such as the ACL, femoral and tibial bones, and cartilage, and the subsequent creation of 3D composite models useful for accurately tracing the entire morphology of the ligament, including its fiber and bundle components, the trajectory between the femur and tibia, and the size, extension, and morphology of its insertions into the bones. CONCLUSION: The implementation of the non-destructive micro-CT method allowed complete visualization of all the different components of the knee specimens. This allowed correlative imaging by micro-CT and histology, accurate planning of histological sections, and virtual anatomical and microstructural analysis. The micro-CT approach provided an unprecedented 3D level of detail, offering a viable means to study ACL anatomy.

Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu.

The use of piezoelectric nanomaterials combined with ultrasound stimulation is emerging as a promising approach for wirelessly triggering the regeneration of different tissue types. However, it has never been explored for boosting chondrogenesis. Furthermore, the ultrasound stimulation parameters used are often not adequately controlled. In this study, we show that adipose-tissue-derived mesenchymal stromal cells embedded in a nanocomposite hydrogel containing piezoelectric barium titanate nanoparticles and graphene oxide nanoflakes and stimulated with ultrasound waves with precisely controlled parameters (1 MHz and 250 mW/cm2, for 5 min once every 2 days for 10 days) dramatically boost chondrogenic cell commitment in vitro. Moreover, fibrotic and catabolic factors are strongly down-modulated: proteomic analyses reveal that such stimulation influences biological processes involved in cytoskeleton and extracellular matrix organization, collagen fibril organization, and metabolic processes. The optimal stimulation regimen also has a considerable anti-inflammatory effect and keeps its ability to boost chondrogenesis in vitro, even in an inflammatory milieu. An analytical model to predict the voltage generated by piezoelectric nanoparticles invested by ultrasound waves is proposed, together with a computational tool that takes into consideration nanoparticle clustering within the cell vacuoles and predicts the electric field streamline distribution in the cell cytoplasm. The proposed nanocomposite hydrogel shows good injectability and adhesion to the cartilage tissue ex vivo, as well as excellent biocompatibility in vivo, according to ISO 10993. Future perspectives will involve preclinical testing of this paradigm for cartilage regeneration.

Exploring In Vivo Models of Musculoskeletal Frailty: A Comprehensive Systematic Review.

Musculoskeletal frailty-a common and debilitating condition linked to aging and chronic diseases-presents a major public health issue. In vivo models have become a key tool for researchers as they investigate the condition's underlying mechanisms and develop effective interventions. This systematic review examines the current body of research on in vivo models of musculoskeletal frailty, without any time constraints. To achieve this aim, we utilized three electronic databases and incorporated a total of 11 studies. Our investigation delves into varied animal models that simulate specific features of musculoskeletal frailty, including muscle loss, bone density reduction, and functional decline. Furthermore, we examine the translational prospects of these models in augmenting our comprehension of musculoskeletal frailty and streamlining the production of groundbreaking therapeutic approaches. This review provides significant insights and guidance for healthcare researchers and practitioners who aim to combat musculoskeletal frailty, ultimately enhancing the quality of life for older adults and individuals affected by this condition.

In Vitro Models of Cell Senescence: A Systematic Review on Musculoskeletal Tissues and Cells.

Ageing is an irreversible and inevitable biological process and a significant risk factor for the development of various diseases, also affecting the musculoskeletal system, resulting from the accumulation of cell senescence. The aim of this systematic review was to collect the in vitro studies conducted over the past decade in which cell senescence was induced through various methods, with the purpose of evaluating the molecular and cellular mechanisms underlying senescence and to identify treatments capable of delaying senescence. Through three electronic databases, 22 in vitro studies were identified and included in this systematic review. Disc, cartilage, or muscle cells or tissues and mesenchymal stem cells were employed to set-up in vitro models of senescence. The most common technique used to induce cell senescence was the addition to the culture medium of tumor necrosis factor (TNF)α and/or interleukin (IL)1ß, followed by irradiation, compression, hydrogen peroxide (H2O2), microgravity, in vitro expansion up to passage 10, and cells harvested from damaged areas of explants. Few studies evaluated possible treatments to anti-senescence effects. The included studies used in vitro models of senescence in musculoskeletal tissues, providing powerful tools to evaluate age-related changes and pathologies, also contributing to the development of new therapeutic approaches.

Bactericidal Activity of Silver-Doped Chitosan Coatings via Electrophoretic Deposition on Ti6Al4V Additively Manufactured Substrates.

Prosthetic reconstruction can serve as a feasible alternative, delivering both functional and aesthetic benefits to individuals with hand and finger injuries, frequent causes of emergency room visits. Implant-related infections pose significant challenges in arthroplasty and osteosynthesis procedures, contributing to surgical failures. As a potential solution to this challenge, this study developed a new class of silver (Ag)-doped chitosan (CS) coatings via electrophoretic deposition (EPD) on osseointegrated prostheses for infection therapy. These coatings were successfully applied to additively manufactured Ti6Al4V ELI samples. In the initial phase, the feasibility of the composite coating was assessed using the Thermogravimetric Analysis (TGA) and Attenuated Total Reflection (ATR) techniques. The optimized structures exhibited impressive water uptake in the range of 300-360%. Codeposition with an antibacterial agent proved effective, and scanning electron microscopy (SEM) was used to examine the coating morphology. Biologically, CS coatings demonstrated cytocompatibility when in direct contact with a fibroblast cell line (L929) after 72 h. When exposed to the Staphylococcus epidermidis strain (ATCC 12228), these coatings inhibited bacterial growth and biofilm formation within 24 h. These findings underscore the significant potential of this approach for various applications, including endoprostheses like hip implants, internal medical devices, and transcutaneous prostheses such as osseointegrated limb prosthetics for upper and lower extremities.

Human Osteoblasts' Response to Biomaterials for Subchondral Bone Regeneration in Standard and Aggressive Environments.

Osteochondral lesions, when not properly treated, may evolve into osteoarthritis (OA), especially in the elderly population, where altered joint function and quality are usual. To date, a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold (OC) has demonstrated good clinical results, although suboptimal subchondral bone regeneration still limits its efficacy. This study was aimed at evaluating the in vitro osteogenic potential of this scaffold, functionalized with two different strategies: the addition of Bone Morphogenetic Protein-2 (BMP-2) and the incorporation of strontium (Sr)-ion-enriched amorphous calcium phosphate (Sr-ACP) granules. Human osteoblasts were seeded on the functionalized scaffolds (OC+BMP-2 and OC+Sr-ACP, compared to OC) under stress conditions reproduced with the addition of H2O2 to the culture system, as well as in normal conditions, and evaluated in terms of morphology, metabolic activity, gene expression, and matrix synthesis. The OC+BMP-2 scaffold supported a better osteoblast morphology and stimulated scaffold colonization, cell activity, and extracellular matrix secretion, especially in the stressed culture environment but also in normal culture conditions, with increased expression of genes related to osteoblast differentiation. In conclusion, the incorporation of BMP-2 into the Col/Col-Mg-HAp scaffold also represents an improvement of the osteochondral scaffold in more challenging conditions, supporting further preclinical studies to optimize it for use in clinical practice.

Relations between Structure/Composition and Mechanics in Osteoarthritic Regenerated Articular Tissue: A Machine Learning Approach.

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.

Gender-Specific Differences in Human Vertebral Bone Marrow Clot.

Recently, our group described the application of vertebral bone marrow (vBMA) clot as a cell therapy strategy for spinal fusion. Its beneficial effects were confirmed in aging-associated processes, but the influence of gender is unknown. In this study, we compared the biological properties of vBMA clots and derived vertebral mesenchymal stem cells (MSCs) from female and male patients undergoing spinal fusion procedures and treated with vBMA clot. We analyzed the expression of growth factors (GFs) in vBMA clots and MSCs as well as morphology, viability, doubling time, markers expression, clonogenicity, differentiation ability, senescence factors, Klotho expression, and HOX and TALE gene profiles from female and male donors. Our findings indicate that vBMA clots and derived MSCs from males had higher expression of GFs and greater osteogenic and chondrogenic potential compared to female patients. Additionally, vBMA-clot-derived MSCs from female and male donors exhibited distinct levels of HOX and TALE gene expression. Specifically, HOXA1, HOXB8, HOXD9, HOXA11, and PBX1 genes were upregulated in MSCs derived from clotted vBMA from male donors. These results demonstrate that vBMA clots can be effectively used for spinal fusion procedures; however, gender-related differences should be taken into consideration when utilizing vBMA-clot-based studies to optimize the design and implementation of this cell therapy strategy in clinical trials.

Piezoelectric ultrasonic debridement as new tool for biofilm removal from orthopedic implants: A study in vitro.

Pulse lavage (PL) debridement is the standard treatment used in Debridement, Antibiotics and Implant Retention (DAIR) for bacterial biofilm removal during acute and early postoperative cases of periprosthetic joint infection (PJI). The failure rate of DAIR is still high due to the inadequacy of PL in removing the biofilm. Ultrasound-based techniques are a well-established tool for PJI diagnosis due to their ability to completely eradicate the biofilm from implant surfaces. Hence, this study investigates the efficiency of a piezoelectric ultrasonic scalpel (PUS) in removing bacterial biofilm from different orthopedic implant materials in vitro and compares the results with PL. Biofilms of methicillin-resistant Staphylococcus aureus strains were grown on titanium alloy (Ti6Al4V ELI), stainless steel (AISI 316L), and ultrahigh molecular weight polyethylene (UHMWPE) disks for 24 h. The disks of each material were divided into three groups: (i) a control group (no lavage/debridement), (ii) a group treated with PL, (iii) a group treated with PUS. The disks were then sonicated for viable cell count to measure the residual biofilm content. Compared to the initial cell count (105 CFU/mL for each material), PL showed a two-log reduction of CFU/mL (p < 0.001 for each material), while for PUS a four-log reduction was found (p < 0.001 for each material). The comparison between the two lavage/debridement displayed a two-log reduction of CFU/mL (p < 0.001 for each material) of PUS compared with PL. Its increased efficiency compared with PL promotes the use of PUS in removing bacterial biofilm from orthopedic implants, suggesting its implementation to improve the success rate of DAIR.

Sarcopenia and osteopenia are independent risk factors for proximal junctional disease after posterior lumbar fusion: Results of a retrospective study.

Study Design: This was a retrospective study. Objective: Since a better understanding of modifiable risk factors for proximal junctional disease (PJD) may lead to improved postoperative outcomes and less need of revision surgery, the aim of the present study is to determine whether sarcopenia and osteopenia are independent risk factors for PJD in patients undergoing lumbar fusion. Summary of Background Data: PJD is one of the most frequent complications following posterior instrumented spinal fusion. It is characterized by a spectrum of pathologies ranging from proximal junctional kyphosis (PJK) to proximal junctional failure (PJF). The etiology of PJD is multifactorial and currently not fully understood. Patient-specific factors, such as age, body mass index, osteoporosis, sarcopenia, and the presence of other comorbidities, can represent potential risk factors. Materials and Methods: A retrospective review of patients, aging 50-85 years, who underwent a short (≤3 levels) posterior lumbar fusion for degenerative diseases was performed. Through magnetic resonance imaging (MRI), central sarcopenia and osteopenia were evaluated, measuring the psoas-to-lumbar vertebral index (PLVI) and the M-score. A multivariate analysis was performed to determine the independent risk factors for PJD, PJK, and PJF. Results: A total of 308 patients (mean age at surgery 63.8 ± 6.2 years) were included. Ten patients (3.2%) developed a PJD and all required revision surgery. Multivariate regression identified PLVI (P = 0.02) and M-score (P = 0.04) as independent risk factors for both PJK (P = 0.02 and P = 0.04, respectively) and PJF (P = 0.04 and P = 0.01, respectively). Conclusions: Sarcopenia and osteopenia, as measured by PLVI and M-score, proved to be independent risk factors for PJD in patients who undergo lumbar fusion for degenerative diseases. Clinical Trial Registration: The present study was approved by the Institutional Review Board, CE AVEC 208/2022/OSS/IOR.

Versatile magnetic configuration for the control and manipulation of superparamagnetic nanoparticles.

The control and manipulation of superparamagnetic nanoparticles (SP-MNP) is a significant challenge and has become increasingly important in various fields, especially in biomedical research. Yet, most of applications rely on relatively large nanoparticles, 50 nm or higher, mainly due to the fact that the magnetic control of smaller MNPs is often hampered by the thermally induced Brownian motion. Here we present a magnetic device able to manipulate remotely in microfluidic environment SP-MNPs smaller than 10 nm. The device is based on a specifically tailored configuration of movable permanent magnets. The experiments performed in 500 µm capillary have shown the ability to concentrate the SP-MNPs into regions characterized by different shapes and sizes ranging from 100 to 200 µm. The results are explained by straightforward calculations and comparison between magnetic and thermal energies. We provide then a comprehensive description of the magnetic field intensity and its spatial distribution for the confinement and motion of magnetic nanoparticles for a wide range of sizes. We believe this description could be used to establish accurate and quantitative magnetic protocols not only for biomedical applications, but also for environment, food, security, and other areas.

Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence.

Osteoarthritis (OA) is a degenerative bone disease that involves the microenvironment and macroenvironment of joints. Progressive joint tissue degradation and loss of extracellular matrix elements, together with different grades of inflammation, are important hallmarks of OA disease. Therefore, the identification of specific biomarkers to distinguish the stages of disease becomes a primary necessity in clinical practice. To this aim, we investigated the role of miR203a-3p in OA progression starting from the evidence obtained by osteoblasts isolated from joint tissues of OA patients classified according to different Kellgren and Lawrence (KL) grading (KL ≤ 3 and KL > 3) and hMSCs treated with IL-1ß. Through qRT-PCR analysis, it was found that osteoblasts (OBs) derived from the KL ≤ 3 group expressed high levels of miR203a-3p and low levels of ILs compared with those of OBs derived from the KL > 3 group. The stimulation with IL-1ß improved the expression of miR203a-3p and the methylation of the IL-6 promoter gene, favoring an increase in relative protein expression. The gain and loss of function studies showed that the transfection with miR203a-3p inhibitor alone or in co-treatments with IL-1ß was able to induce the expression of CX-43 and SP-1 and to modulate the expression of TAZ, in OBs derived from OA patients with KL ≤ 3 compared with KL > 3. These events, confirmed also by qRT-PCR analysis, Western blot, and ELISA assay performed on hMSCs stimulated with IL-1ß, supported our hypothesis about the role of miR203a-3p in OA progression. The results suggested that during the early stage, miR203a-3p displayed a protective role reducing the inflammatory effects on CX-43, SP-1, and TAZ. During the OA progression the downregulation of miR203a-3p and consequently the upregulation of CX-43/SP-1 and TAZ expression improved the inflammatory response and the reorganization of the cytoskeleton. This role led to the subsequent stage of the disease, where the aberrant inflammatory and fibrotic responses determined the destruction of the joint.

Cell Adhesion and Initial Bone Matrix Deposition on Titanium-Based Implants with Chitosan-Collagen Coatings: An In Vitro Study.

In orthopedics, titanium (Ti)-alloy implants, are often considered as the first-choice candidates for bone tissue engineering. An appropriate implant coating enhances bone matrix ingrowth and biocompatibility, improving osseointegration. Collagen I (COLL) and chitosan (CS) are largely employed in several different medical applications, for their antibacterial and osteogenic properties. This is the first in vitro study that provides a preliminary comparison between two combinations of COLL/CS coverings for Ti-alloy implants, in terms of cell adhesion, viability, and bone matrix production for probable future use as a bone implant. Through an innovative spraying technique, COLL-CS-COLL and CS-COLL-CS coverings were applied over Ti-alloy (Ti-POR) cylinders. After cytotoxicity evaluations, human bone marrow mesenchymal stem cells (hBMSCs) were seeded onto specimens for 28 days. Cell viability, gene expression, histology, and scanning electron microscopy evaluations were performed. No cytotoxic effects were observed. All cylinders were biocompatible, thus permitting hBMSCs' proliferation. Furthermore, an initial bone matrix deposition was observed, especially in the presence of the two coatings. Neither of the coatings used interferes with the osteogenic differentiation process of hBMSCs, or with an initial deposition of new bone matrix. This study sets the stage for future, more complex, ex vivo or in vivo studies.

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.

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.

RNA Extraction from Cartilage: Issues, Methods, Tips.

The increase in degenerative diseases involving articular cartilage has pushed research to focus on their pathogenesis and treatment, exploiting increasingly complex techniques. Gene expression analyses from tissue are representative of the in vivo situation, but the protocols to be applied to obtain a reliable analysis are not completely cleared through customs. Thus, RNA extraction from fresh samples and specifically from musculoskeletal tissue such as cartilage is still a challenging issue. The aim of the review is to provide an overview of the techniques described in the literature for RNA extraction, highlighting limits and possibilities. The research retrieved 65 papers suitable for the purposes. The results highlighted the great difficulty in comparing the different studies, both for the sources of tissue used and for the techniques employed, as well as the details about protocols. Few papers compared different RNA extraction methods or homogenization techniques; the case study reported by authors about RNA extraction from sheep cartilage has not found an analog in the literature, confirming the existence of a relevant blank on studies about RNA extraction from cartilage tissue. However, the state of the art depicted can be used as a starting point to improve and expand studies on this topic.

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.