Nicolò Rossi

Background: Hip osteoarthritis is a highly prevalent degenerative condition and a leading indication for total hip arthroplasty (THA). As anterior approaches have gained popularity, optimizing postoperative rehabilitation according to the muscles involved in recovery has become increasingly relevant. However, evidence regarding muscle-specific rehabilitation following the Anterior Minimally Invasive Surgery (AMIS) approach remains limited. Objectives: This study aimed to evaluate whether rehabilitation protocols specifically targeting the hip flexors or abductors could improve postoperative functional recovery compared with standard rehabilitation following AMIS THA. Methods: This retrospective single-center study included 29 patients aged 50–80 years with BMI < 30 kg/m² undergoing unilateral THA through the AMIS approach. The cohort included 14 men and 15 women. Patients were non-randomly allocated according to clinical and organizational factors to standard rehabilitation (ST; n = 10), a hip flexor-focused protocol (SP1; n = 10), or a hip abductor-focused protocol (SP2; n = 9). Postoperative recovery was evaluated using clinical, functional, and patient-reported outcome measures. Rehabilitation was supervised by physiotherapists. Outcomes included goniometric hip range of motion, dynamometer-measured hip flexor and abductor strength, Timed Up and Go (TUG), Visual Analogue Scale (VAS), Harris Hip Score (HHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), and SF-12. Longitudinal outcomes were analyzed using two-factor models assessing time, rehabilitation group, and their interaction, with post hoc comparisons where appropriate. Statistical significance was set at p < 0.05. Results: Of the 29 initially enrolled patients, 26 completed the study assessments and were included in the final analysis (ST, n = 9; SP1, n = 10; SP2, n = 7). Significant improvements over time were observed for hip flexion and internal rotation ROM, abductor strength, TUG, VAS, HOOS, and HHS. No consistent superiority of either targeted protocol over standard rehabilitation was identified. Postoperative improvements in hip range of motion, muscle strength, mobility, pain, and functional performance were observed over time across the study cohort. Although no protocol demonstrated statistically significant superiority in range of motion or functional outcomes, all three groups showed postoperative improvement over time following AMIS THA. Conclusions: All rehabilitation groups improved during postoperative recovery, but neither the flexor- nor abductor-focused protocol demonstrated superiority over standard rehabilitation. Given the small sample size and non-randomized design, these findings are preliminary and hypothesis-generating and require confirmation in adequately powered randomized studies. Because the targeted protocols also involved a greater overall number of prescribed exercises, the present design cannot distinguish the effects of muscle-specific targeting from those of greater exercise exposure.

Osteoarthritis (OA) represents a significant challenge in both orthopedic research and clinical practice, necessitating the development of effective therapeutic strategies. Here, we describe an ex vivo model based on osteochondral (OCh) explants housed in a three‐dimensional printed device that enables the separation of bone and cartilage compartments. Our model demonstrates effective partitioning, as confirmed by significant differences in measurements of tissue‐specific markers. The markers included matrix metalloproteinase (MMP) activity and sulfated glycosaminoglycan (sGAG) release for cartilage and alkaline phosphatase (ALP) activity, tartrate‐resistant acid phosphatase (TRAP) activity, and osteocalcin (OC) levels for bone. The cartilage compartment of OCh explants was exposed to inflammatory stimuli, to mimic the OA‐related microenvironment, using 10 ng/mL TNFα and 1 ng/mL IL‐1β. Cytokine administration was coupled with secretome (or conditioned medium, CM) treatment obtained from 5 × 10 ⁵ naïve or cytokine‐primed adipose‐derived mesenchymal cells (CM and pCM). After 3 days, inflammatory cytokines induced a significant upregulation of MMP activity, effectively countered by both CM and pCM, alongside a modest increase in sGAG release. No major changes were detected in the bone counterpart. This study holds dual significance: firstly, the development and preliminary assessment of a human‐based ex vivo model in accordance with 3Rs (Replacement, Reduction, Refinement) principles in preclinical research; secondarily, the evidence of an anti‐catabolic potential of the adipose‐derived mesenchymal cell secretome contributes, within a broader research context, to hypothesizing its potentiality in counteracting OA‐associated hallmarks, with possible applications at early onset to mitigate the degenerative processes of this pathology. Trial Registration: ClinicalTrials.gov identifier: NCT04223622

Purpose: To evaluate the safety and efficacy of intra‐articular autologous transplantation of adipose‐derived connective tissue micrografts rich in stromal vascular fraction (CTM‐SVF), obtained using an enzyme‐free system (Hy‐Tissue® SVF) for knee osteoarthritis (OA). Methods: Thirty patients (mean age of 53.3 ± 6.4 years) with Kellgren–Lawrence grade I to III knee OA received a single intra‐articular injection of autologous CTM‐SVF prepared with the Hy‐Tissue SVF concentration system. Follow‐ups were set at 3‐, 6‐ and 12‐month postinjection. Outcome measures included knee injury and osteoarthritis outcome score (KOOS), pain relief (NRS‐11), quality of life (EQ‐5D index), magnetic resonance imaging (MRI) scans (whole‐organ magnetic resonance imaging score—WORMS, T2 mapping), OA serum biomarkers, safety and local tolerability. Results: One patient discontinued prematurely. KOOS improved significantly, with the highest mean score (68.7 ± 14.9) at 3 months and the majority of patients achieving a ≥ 9‐point increase from baseline. Results were maintained through 12 months. NRS‐11 and EQ‐5D also improved through 12 months, with more than 80% of patients meeting the NRS‐11 MCID at every timepoint. EQ‐VAS, however, showed only a modest responder rate (10%). MRI revealed improvements in T2 relaxation times, while OA serum biomarkers (evaluated at 3 months postinjection) indicated a significant decrease in Procollagen II N‐Terminal Propeptide levels. No device‐related adverse events (ADEs) were observed. The majority of adverse events (AEs) recorded during the study were mild and transient, none were classified as serious and resolved within a short period. Conclusions: Intra‐articular injection of autologous CTM‐SVF, obtained the Hy‐Tissue‐SVF system, proved to be effective and safe for managing knee OA symptoms and improving mobility, up to 12 months. Clinically significant pain relief and quality of life improvement were observed, particularly in the short term, with a gentle reduction of the scores over time. Larger controlled trials are required to confirm treatment durability. Level of Evidence: Level II.

Osteochondral regeneration remains a major clinical challenge due to the complex architecture and biomechanical demands of the osteochondral unit. Bioactive hydrogels have emerged as promising materials capable of supporting repair through their capacity to mimic the extracellular matrix (ECM), enable cell encapsulation, and deliver bioactive cues. However, recent insights reveal that simply engineering hydrogels for structural and cellular support is insufficient. A new paradigm is emerging—one that embraces the complexity of the osteochondral niche by integrating immunomodulatory and mechanobiological cues into biomaterial design. In particular, the hydrogel’s capacity to modulate macrophage polarization and support the immunoregulatory function of mesenchymal stem cells (MSCs) is critical to orchestrate regenerative outcomes. Simultaneously, the mechanical properties of hydrogels—such as stiffness, porosity, and viscoelasticity—can profoundly influence stem cell fate and local tissue morphogenesis. This review discusses recent advances in hydrogel-based strategies for osteochondral repair, highlighting the interplay between immunological signals and the mechanical microenvironment, and calls for a shift from reductionist tissue-engineering approaches to systems-level design of tunable, immuno-mechanobiological microenvironments.

Background/Objectives: Aseptic loosening is a major challenge in hip and knee arthroplasty. While radiostereometric analysis (RSA) is the gold standard for detecting early migration, it is static, costly, and requires metal beads. Provocation CT-based analysis studies implants under physiological stresses and offers a marker-free alternative with comparable accuracy. This systematic review evaluates its effectiveness, cost, and role in orthopedic imaging. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Three databases were searched, with no date restrictions, using keywords related to the research area. The risk of bias was assessed using the RoB-1 tool. Results: The initial search identified 42 studies, with 6 ultimately included in the review. These studies involved 198 patients with an average age of 65.0 years. Provocation CT demonstrated higher sensitivity and specificity than standard radiographs, particularly in cases with inconclusive X-rays. Additionally, the radiation dose for CT scans varied across studies, with effective doses ranging from 0.2 mSv to 4.5 mSv per scan. Compared to X-ray, CT-based methods showed comparable or superior performance in motion detection, though direct clinical comparisons with RSA remain lacking. Conclusions: Provocation CT-based analysis is a valuable diagnostic tool for early detection of implant loosening, offering a potentially feasible, accurate, and cost-effective alternative to traditional methods. However, standardized protocols, broader economic evaluations, and prospective multicenter trials are needed to confirm its routine clinical applicability.

Peripheral nerve injuries affect 13–23 per 100,000 people annually in the U.S. and often result in motor and sensory deficits. Microsurgical suture repair (SR) is the standard treatment but is technically challenging and associated with complications. Photochemical tissue bonding (PTB), which uses light and a photoactivated dye to bond collagenous tissues, offers a promising alternative. We compared PTB with commercially available collagen membranes for SR and PTB using cryopreserved human amnion (HAM) in a rat sciatic nerve transection model. In total, 75 Lewis rats underwent nerve repair with one of five methods: SR, PTB-HAM, PTB with commercial collagenous membranes (human amnion monolayer (AML), human amnion–chorion–amnion trilayer (ATL), or swine intestinal submucosa (SIS)). Functional recovery was assessed with walking tracks and the Static Sciatic Index (SSI) at days 30, 60, 90, and 120; histological evaluations at days 30 and 120 examined inflammation, axon density, and fascicle structure. No significant differences in SSI scores were found between groups, though PTB-AML and PTB-SIS improved over time. Histology showed inflammation at day 30 that decreased by day 120. Histomorphometry revealed similar axon regeneration across groups. These results suggest that PTB with commercial membranes is a viable alternative to SR.

Strategies to repair the meniscus have achieved limited success; thus, a cell-based therapy combined with an appropriate biocompatible scaffold could be an interesting alternative to overcome this issue. The aim of this project is to analyze different cell populations and a collagen gel scaffold as a potential source for meniscus tissue engineering applications. Dermal fibroblasts (DFs) and mesenchymal stem cells (MSCs) isolated from adipose tissue (ASCs) or bone marrow (BMSCs) were analyzed. Two different fibro-chondrogenic media, M1 and M2, were tested, and qualitative and quantitative analyses were performed. Significant increases in glycosaminoglycans (GAGs) production and in fibro-cartilaginous marker expression were observed in MSCs in the presence of M1 medium. In addition, both ASCs and BMSCs cultured in M1 medium were used in association with the collagen hydrogel (MSCs-SCF) for the development of an in vitro meniscal-like tissue. Significant up-regulation in GAGs production and in the expression of aggrecan, collagen type I, and collagen type II was observed in BMSCs-SCF. This study improves knowledge of the potential of combining undifferentiated MSCs with a collagen gel as a new tissue engineering strategy for meniscus repair.

Photochemical sealing of a nerve wrap over the repair site isolates and optimizes the regenerating nerve microenvironment. To facilitate clinical adoption of the technology, we investigated photosealed autologous tissue in a rodent sciatic nerve transection and repair model. Rats underwent transection of the sciatic nerve with repair performed in three groups: standard microsurgical neurorrhaphy (SN) and photochemical sealing with a crosslinked human amnion (xHAM) or autologous vein. Functional recovery was assessed at four-week intervals using footprint analysis. Gastrocnemius muscle mass preservation, histology, and nerve histomorphometry were evaluated at 120 days. Nerves treated with a PTB-sealed autologous vein improved functional recovery at 120 days although the comparison between groups was not significantly different (SN: −58.4 +/− 10.9; XHAM: −57.9 +/− 8.7; Vein: −52.4 +/− 17.1). Good muscle mass preservation was observed in all groups, with no statistical differences between groups (SN: 69 +/− 7%; XHAM: 70 +/− 7%; Vein: 70 +/− 7%). Histomorphometry showed good axonal regeneration in all repair techniques. These results demonstrate that peripheral nerve repair using photosealed autologous veins produced regeneration at least equivalent to current gold-standard microsurgery. The use of autologous veins removes costs and foreign body concerns and would be readily available during surgery. This study illustrates a new repair method that could restore normal endoneurial homeostasis with minimal trauma following severe nerve injury.

Purpose: The purpose of this study was to investigate the influence of sex on patients undergoing total hip arthroplasty (THA) for hip osteoarthritis (HOA), aiming to assess the clinical and functional outcomes using patient‐reported outcome measures (PROMs).Methods: A retrospective analysis of patients undergoing THA at Ospedale Galeazzi‐Sant'Ambrogio between 2016 and 2022 was conducted. Inclusion criteria encompassed Kellgren–Lawrence grade III or IV HOA, with preoperative and 12‐month postoperative PROMs. Enroled patients have been selected from a larger cohort without matching design for confounders. The analyses were performed using R software v4.0.3 (R Core Team) and data distributions were assessed using the Shapiro–Wilk normality test.Results: One hundred ninety patients (72 male and 118 female) who had both preoperative and postoperative PROMs have been analysed from our institutional prosthesis registry (Datareg). Baseline and 12‐month post‐THA PROMs showed significant improvements overall. VAS score dropped notably from baseline to 3 months postsurgery (7.1 ± 2.1 vs. 0.9 ± 1.7). Functional and mental PROMs, including Harris Hip Score‐functional (HHS‐F), Harris Hip Score‐total (HHS‐t), SF‐12PS and SF‐12MS, exhibited substantial improvements post‐THA. Stratifying by sex, males had lower baseline VAS, higher HHS‐F, SF‐12MS and hip disability and osteoarthritis outcome score‐physical function short form (HOOS‐PS). At 12 months, males displayed significantly better VAS, HHS‐F, SF‐12PS and HOOS‐PS scores. Complication rates were minimal (1.5%), with stable rates across genders, mostly involving dislocation and periprosthetic fractures. Implant survival at 12 months reached an impressive 99%.Conclusion: THA remains an effective treatment for severe HOA. However, females presented with worse baseline conditions and showed relatively less improvement at 1‐year postsurgery compared to males. This difference could be attributed to physiological and psychosocial factors associated with sex, including hormonal changes, muscle mass decline and perception of pain. Longer follow‐ups and prospective studies are necessary to validate these findings and facilitate personalised approaches in HOA treatment, emphasising the need for careful consideration of sex‐related variables in clinical decision‐making for THA patients.Level of Evidence: Level III.