Dong Jin Ryu

Background and Objectives: Postoperative alignment after medial open-wedge high tibial osteotomy (MOWHTO) reflects both osseous correction and load-dependent joint response. We evaluated the internal radiographic performance of a prespecified threshold-based latent medial laxity (LML) adjustment and explored alternative deduction models. Materials and Methods: Seventy-two consecutive eligible knees were retrospectively analyzed. LML, defined operationally as the difference between joint-line convergence angles on supine valgus-stress and standing radiographs, was treated as a composite load-and-stress response. One-third of LML was deducted from the target correction angle when LML was ≤5°, and one-half when LML was >5°. The primary outcome was 1-year hip–knee–ankle (HKA) error within ±1.0°. Change in mechanical medial proximal tibial angle (ΔmMPTA) served as a radiographic proxy for executed osseous correction. Alternative deduction rules were compared by internal counterfactual analysis with leave-one-out cross-validation for fitted models. Results: Fifty-two knees (72.2%; 95% CI, 60.4–82.1%) were within ±1.0° of target. Mean signed error was −0.38 ± 0.95° (p = 0.001), with Bland–Altman limits of agreement from −2.25° to 1.49°. Mean ΔmMPTA was 6.03 ± 2.59°, versus a planned osseous correction of 6.81 ± 1.41°; the execution proxy averaged −0.78 ± 2.13° (p = 0.003). The residual planning component averaged +0.40 ± 2.04° (p = 0.098). In the internal comparison, the threshold rule yielded an MAE of 0.76° and 72.2% within ±1.0°, versus 1.79° and 41.7% with no adjustment. An exploratory continuous model (deduction = −1.77 + 0.736 × LML) yielded an MAE of 0.66° and 79.2% within ±1.0° (leave-one-out MAE, 0.68°). Conclusions: Threshold-based LML adjustment reproduced the individualized 1-year HKA target within ±1.0° in 72.2% of knees. This simple method appears feasible for preoperative planning; however, the small target-relative undercorrection bias warrants further refinement and prospective comparative validation.

Objectives To evaluate whether an 8-week smartphone-based multidisciplinary digital therapeutic (DTx) combining exercise and cognitive–behavioural therapy reduced usual knee pain at 8 weeks compared with education and exercise instruction in chronic patellofemoral pain (PFP). Methods This multicentre, parallel-group randomised controlled trial included 216 participants with chronic PFP, defined as anterior or retropatellar pain lasting at least 3 months with activity-related provocation, recruited from orthopaedic outpatient clinics at 10 hospitals in the Republic of Korea. Participants were randomly assigned to the DTx group (MORA Cure PFP) or a control group receiving PFP-related education, one-time exercise instruction, printed materials and self-monitoring exercise diaries. The DTx intervention included personalised home-based exercises, weekly cognitive–behavioural sessions and self-reflective daily worksheets. Outcomes were assessed at baseline, 4, 8 and 12 weeks. The primary endpoint was usual pain at 8 weeks, measured using a 0–100 mm visual analogue scale (VAS). Secondary outcomes included worst pain, knee function (Anterior Knee Pain Scale; AKPS), health-related quality of life assessed using the 5-level EQ-5D version (EQ-5D-5L) and the EQ visual analogue scale (EQ VAS), and psychological distress (Patient Health Questionnaire-9 and Pain Catastrophizing Scale (PCS)). Longitudinal changes were analysed using linear mixed-effects models. Results For the primary endpoint, usual pain at week 8 favoured the DTx group (between-group mean difference −12.5 mm, 95% CI −17.1 to −7.8). Secondary outcomes at week 8 also favoured the DTx group, including worst pain (−10.7 mm, 95% CI −15.9 to −5.4), knee function (AKPS, 5.2 points, 95% CI 2.7 to 7.7), health-related quality of life (EQ VAS 10.7 points, 95% CI 7.1 to 14.4) and pain catastrophising (PCS, −1.8 points, 95% CI −3.3 to −0.3). Exercise adherence exceeded 80%, with no device-related or intervention-related serious adverse events reported. Conclusion An 8-week smartphone-based multidisciplinary DTx programme reduced usual pain at 8 weeks compared with education and exercise instruction in patients with chronic PFP, with improvements in pain, knee function, health-related quality of life and psychological outcomes. These findings support the potential role of an integrated DTx package for delivering exercise and cognitive–behavioural support in PFP care. Trial registration number NCT06260865.

Mesenchymal stem cells (MSCs) spontaneously assemble into three-dimensional (3D) spheroids under matrix-deficient conditions such as the synovial cavity, although their functional significance has yet to be fully elucidated. In this study, we used concave microwell cultures to promote the spontaneous aggregation of adipose-derived MSCs (ASCs) from OA patients, thereby mimicking the intra-articular microenvironment. We analyzed the paracrine factors of ASC aggregates and compared it with that of conventional 2D monolayer cultures. Notably, 3D aggregation significantly increased the secretion of HGF and VEGF, whereas FGF2 levels remained relatively unchanged. These results indicate that the structural characteristics of ASC aggregates enhance the secretion of key paracrine factors involved in angiogenesis and tissue repair. To functionally evaluate the biological relevance of the secreted factors, conditioned media (CM) from ASC aggregates were applied to human articular chondrocytes. The CM significantly promoted chondrocyte proliferation, an effect that was abolished by the addition of HGF-neutralizing antibodies, thereby highlighting HGF as a central mediator of the regenerative response. Additionally, we further explored whether extracellular factors could modulate growth factor expression such as HGF. In this context, we investigated the impact of low-concentration hyaluronic acid (HA), a key synovial component widely used in OA treatment. Co-treatment with HA not only amplified the expression and secretion of HGF, VEGF, and FGF2, but also promoted ASC proliferation. ASCs forming functional aggregates may exert regenerative effects as active paracrine modulators, and the addition of low-dose hyaluronic acid is expected to further enhance this function, offering a promising strategy for MSC-based osteoarthritis therapy.

Background: Remnant tensioning (RT) anterior cruciate ligament (ACL) reconstruction has been reported to have excellent postoperative outcomes for femoral-side tears. However, the influence of remnant continuity (RC) on the postoperative results after RT ACL reconstruction remains unclear. Purpose: To investigate the effects of RC on the postoperative clinical, radiological, and second-look arthroscopic outcomes after RT ACL reconstruction for femoral-side ACL tears. Study Design: Cohort study; Level of evidence, 3. Methods: This study included 94 patients who underwent RT ACL reconstruction using the hamstring tendon for femoral-side ACL tears between 2015 and 2020. The patients were divided into 2 groups according to the continuity of the remnant tissue: RC (n = 50) and remnant discontinuity (RD) (n = 44). Stability tests, including the Lachman and pivot-shift tests, side-to-side difference on Telos stress radiographs and KT-2000 arthrometer, patient-reported outcome measurements (PROMs), and graft status on postoperative magnetic resonance imaging (MRI) and second-look arthroscopy were evaluated. Results: Results of all stability tests and PROMs significantly improved postoperatively. The mean follow-up periods were 35.3 and 36.8 months in the RC and RD group, respectively. The 2 groups showed no statistically significant differences in stability outcomes or PROMs. Furthermore, the RC and RD groups showed comparable postoperative graft status on postoperative MRI and second-look arthroscopy. Conclusion: RT ACL reconstruction for RD between the femoral insertion site and ACL tissue showed comparable postoperative outcomes, including stability test, PROMs, postoperative MRI, and second-look arthroscopic data, to surgery for RC in femoral-side tears.

Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression.

For many years, sustained-release drug delivery systems (SRDDS) have emerged as a featured topic in the pharmaceutical field. Particularly for chronic diseases, such as osteoarthritis, there is a lot of demand for SRDDS because of the long treatment period and repetitive medication administration. Thus, we developed an injectable PLGA-F127 microsphere (MS) that is capable of the in situ conversion to an implant. The microprecipitation method for PLGA-F127 MS was established, and the physicochemical stability of the products was confirmed. The microspheres were assembled into a single mass in 37 °C aqueous conditions and showed a remarkably delayed drug release profile. First, the release started with no significant initial burst and lagged for 60 days. After that, in the next 40 days, the remaining 75% of the drugs were constantly released until day 105. We expect that our PLGA-F127 MS could be employed to extend the release period of 2 months of medication to 4 months. This could be a valuable solution for developing novel SRDDS for local injections.

Lim CW, et al. Yonsei Med J. 2024 Jun;65:e40. https://doi.org/10.3349/ymj.2023.0456

Jeon YS, et al. Clin Orthop Surg. 2023 Aug;15(4):616-626. https://doi.org/10.4055/cios22397