Freeze-dried noncoagulating platelet-derived factor concentrate is a safe and effective treatment for early knee osteoarthritis.

PURPOSE: While a wide variety of platelet-rich plasma (PRP) solutions has been developed, innovation continues. In this case, the freeze-dried platelet factor concentrate (PFC-FD) represents another step in PRP refinement. The preparation of PFC-FD at a central laboratory with freeze drying for shelf stabilization should provide additional quality improvements if clinical effectiveness can be demonstrated. Therefore, this study was undertaken to assess the safety and effectiveness of PFC-FD in a prospective open-label trial of patients suffering from knee osteoarthritis (OA). METHODS: 312 consecutive knee OA patients (67% female, mean age 63 ± 10 years), were prospectively recruited in an outpatient knee clinic in Japan. Of these, 10 (3.2%) were lost to follow-up at < 12 months and 17 (5.5%) sought additional knee therapy during the follow-up period. The primary outcome of interest was achievement of the OMERACT-OARSI responder criteria with secondary outcomes of adverse events and PROMs scores 1, 3, 6, 12 months following a single PFC-FD injection. RESULTS: 285 patients (91%) completed 12 month PROMs. The 17 who sought additional therapy were considered failures leaving an effective sample size of 302 for our primary outcome in which 62% of patients achieved OMERACT-OARSI responder status by 12 months. This varied by OA class with Kellgren-Lawrence grade 4 patients 3.6 times less likely to be responders than grade 1-2 patients. 6% of patients experienced a non-serious adverse event, primarily pain or swelling at the injection site. CONCLUSIONS: PFC-FD provides an observable clinical improvement in 62% of knee OA patients at 12 months post-injection with very little risk of any clinically relevant adverse event. Of course, nearly 40% of patients did not experience an observable clinical improvement, primarily among those with worse KL grades. LEVEL OF EVIDENCE: Therapeutic, Level II.

Open wedge high tibial osteotomy does not decrease patellar height relative to femur: A three-dimensional computer model analysis.

BACKGROUND: Patellar height, which decreases after open wedge high tibial osteotomy (OWHTO), has conventionally been assessed by tibial references using lateral radiographs of the knee; however, changes in the proximal tibia shape after OWHTO may affect this method. We aimed to evaluate the changes in patellar height position relative to the transepicondylar axis of the femur after OWHTO using in vivo three-dimensional (3D) computer models. METHODS: Fourteen patients who underwent 3D magnetic resonance imaging (MRI) at 30° and 50° knee flexion before OWHTO and after hardware removal were included. 3D computer models of the knee were created from the MRI scans and superimposed over the images taken in each position using voxel-based registration. For patellar height evaluation, a patellar reference point was established at each flexion angle and the femoral condylar planes (FCP) were set, including the transepicondylar axis. The patellar center angle was defined as the angle between an FCP that included the top of the intercondylar notch and an FCP that included the patellar reference point. The patellar center angle was evaluated at 30° and 50° knee flexion before and after OWHTO. RESULTS: The patellar center angle at 30° and 50° knee flexion did not significantly decrease after OWHTO, whereas the Caton-Deschamps index and Blackburne-Peel index based on tibia-referenced measurements significantly decreased postoperatively. CONCLUSION: Patellar height position relative to the femur in the 3D computer model did not decrease after OWHTO, whereas tibia-referenced conventional radiographic measurements significantly decreased. When evaluating patellar height, characteristics of each parameter should be considered.

Improved responsiveness for JKOOS+ compared to KOOS in Japanese patients undergoing total knee arthroplasty.

BACKGROUND: Existing knee related patient reported outcome measurements (PROMs) have overwhelmingly been developed and validated in western chair-based societies, suggesting a potential for a western bias in PROMs evaluation of patients with knee conditions. We, therefore, endeavor to evaluate the responsiveness of the previously developed culturally relevant Japanese version of the knee injury and osteoarthritis outcome score (JKOOS+). METHODS: We enrolled 114 patients scheduled for total knee arthroplasty (TKA) across 8 knee clinics in Japan. Patients completed the Oxford Knee Score (OKS) and JKOOS + both at the time of enrollment and again 1-year post-TKA. Responsiveness was evaluated using effect size and standardized response mean (SRM). An effect size or SRM >0.8 is considered adequately responsive. We further tested the difference in responsiveness between the original Japanese language KOOS activities of daily living (ADL) domain and the novel Japanese ADL (JADL) domain using the modified Jacknife test. RESULTS: All domains were adequately responsive with the exception of the KOOS sports and recreation domain, which has previously been ignored by TKA researchers due to its lack of applicability to elderly patients undergoing TKA. The JADL domain outperformed the ADL domain in both effect size (1.51 v. 1.45) and SRM (1.67 v. 1.57) (p < 0.001). The novel Knee Flexion (KF) domain was adequately responsive, though less responsive than other domains except sports and recreation (p < 0.01 v. all other PROMs domains). CONCLUSIONS: The JKOOS+ JADL domain is significantly more responsive than the Europe-developed ADL domain to TKA in Japanese knee patients suffering from knee osteoarthritis (OA). The KF domain, unique to the JKOOS+ and intended to assess difficulty with knee flexion, is adequately responsive to TKA in Japanese patients suffering from OA.

Current hip cartilage regeneration/repair modalities: a scoping review of biologics and surgery.

PURPOSE: The rapidly growing and emerging nature of biologics have made indications for regenerative and reparative hip therapies ever changing, with at times only early-stage evidence for their use. The purpose of this study was to review and summarize the currently available data on the management of hip cartilage injuries and osteoarthritis. METHODS: A scoping review of the available scientific literature for hip biologics was performed, with available evidence for hyaluronic acid (HA), platelet rich plasma (PRP), stem/stromal cells, microfracture, mosaicplasty, osteochondral allograft, and cell-based therapies investigated. RESULTS: To date, there exist better guidelines and further consensus concerning knee joint biologic treatments than the hip due to a greater number of studies as well as the more recent emergence of hip preservation approaches. However, increasing evidence is available for the selective implementation of biologics on an individualized basis with attention to lesion size and location. CONCLUSION: Orthopedic surgeons are at an exciting crossroads in medicine, where hip biologic therapies are evolving and increasingly available. Timetested interventions such as arthroplasty have shown good results and still have a major role to play but newer, regenerative approaches have the potential to effectively delay or reduce the requirement for such invasive procedures.

Does Internal Fixation for Unstable Osteochondritis Dissecans of the Skeletally Mature Knee Work? A Systematic Review.

PURPOSE: To report the rate of radiographic union, patient-reported outcomes, complications, and reoperations after internal fixation of unstable osteochondritis dissecans (OCD) in the skeletally mature knee. METHODS: A literature search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Patients were included if they were skeletally mature and underwent internal fixation of an unstable OCD lesion of the knee. Risk of bias assessment was performed using the Methodological Index for Non-randomized Studies scoring system. Surgical technique, rate of union, patient-reported outcomes, complications, and reoperations were collected. RESULTS: Thirteen studies resulted in 148 patients (150 knees) for inclusion. Patient age ranged from 14 to 45 years. Numerous fixation procedures were used, including biodegradable devices (rods, pins, nails, and screws), metal screws, Kirschner wire, and autologous bone sticks. Overall, reported outcome measures were heterogeneous in nature. The rate of radiographic healing ranged from 67% to 100% across 6 studies. Improved subjective results and Hughston criteria on final follow-up ranged from 83% to 100% across 4 studies each. Mean postoperative Lysholm scores ranged from 42 to 98 in studies that reported them. Both complication and reoperation rates ranged from 0% to 44%. The most commonly performed reoperations were loose body excision and cartilage resurfacing procedures. CONCLUSIONS: A variety of surgical techniques are available for treatment of unstable OCD lesions in the skeletally mature knee. In this systematic review, internal fixation of the native fragment showed acceptable rates of radiographic union and improved patient-reported outcomes relative to other techniques. LEVEL OF EVIDENCE: Level IV, systematic review of level III-IV studies.

Development and validation of a culturally relevant Japanese KOOS.

INTRODUCTION: The Knee Injury and Osteoarthritis Outcomes Survey (KOOS) has been translated into 50 languages worldwide. These translations have adhered to guidelines for cross cultural adaptation of health surveys. However, after release of the Japanese KOOS (JKOOS) we discovered the JKOOS was not fully culturally relevant to Japanese patients. Therefore, we undertook the development and validation of the JKOOS+. METHODS: We completed this project in 2 phases across 9 hospitals. In Phase 1, 187 surgically naïve patients with knee pain were asked about activities limited by their knee pain. An expert panel reconciled these activities against existing KOOS items to identify novel items. In Phase 2, 241 surgically naïve patients with knee pain were administered the Japanese Oxford Knee Survey, JKOOS, and these novel items. An iterative Rasch analysis was used to test item fit of these novel items within the KOOS Activities of Daily Living (ADL) domain and a potential new domain. Unidimensionality was assessed using principle component analysis. Internal consistency (Cronbach's alpha) and external validity (Spearman's Correlations) were assessed for Japanese ADL (J-ADL) and the novel domain. RESULTS: Phase 1 identified 4 activities relevant to Japanese knee patients: sitting seiza, using a Japanese toilet, climbing hills, and getting on/off a bus/train. In Phase 2, climbing hills and bus/train were well fit in JADL. Seiza and using a Japanese toilet were not well fit in J-ADL, yet both require deep knee flexion so a knee flexion (KF) domain was constructed by considering all KOOS items that require knee flexion using an iterative Rasch model. An 8 item KF domain emerged. Both J-ADL and KF were deemed to be unidimensional with high internal consistency (Cronbach's alpha >0.92) and external validity (Spearman Correlations 0.723-0.929). CONCLUSIONS: We have successfully developed and validated JKOOS+, a more culturally relevant knee survey for Japanese patients.

Editorial Commentary: Pursue the Anatomy of the Knee Anterior Cruciate Ligament Footprint.

The paradigm of anterior cruciate ligament reconstruction has shifted from nonanatomic/isometric to anatomic reconstruction so as to mimic the native anterior cruciate ligament anatomy, as well as its function. A triple-bundle reconstruction technique more precisely mimics the native anterior cruciate ligament. On the other hand, functional advantages of triple-bundle reconstruction have not been fully elucidated. Comparative clinical studies between reconstruction techniques are needed.

Injectable Systems for Intra-Articular Delivery of Mesenchymal Stromal Cells for Cartilage Treatment: A Systematic Review of Preclinical and Clinical Evidence.

Stem cell-based therapy is a promising approach to treat cartilage lesions and clinical benefits have been reported in a number of studies. However, the efficacy of cell injection procedures may be impaired by cell manipulation and damage as well as by cell dissemination to non-target tissues. To overcome such issues, mesenchymal stromal cell (MSC) delivery may be performed using injectable vehicles as containment systems that further provide a favorable cell microenvironment. The aim of this systematic review was to analyze the preclinical and clinical literature on platelet-rich plasma (PRP), hyaluronic acid (HA), and hydrogels for the delivery of MSCs. The systematic literature search was performed using the PubMed and Web of science databases with the following string: "(stem cells injection) AND (platelet rich plasma OR PRP OR platelet concentrate OR biomaterials OR hyaluronic acid OR hydrogels)": 40 studies (19 preclinical and 21 clinical) met the inclusion criteria. This review revealed an increasing interest on the use of injectable agents for MSC delivery. However, while negligible adverse events and promising clinical outcomes were generally reported, the prevalence of low quality studies hinders the possibility to demonstrate the real benefits of using such injectable systems. Specific studies must be designed to clearly demonstrate the added benefits of these systems to deliver MSCs for the treatment of cartilage lesions and osteoarthritis.

Responsiveness of the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Oxford Knee Score (OKS) in Japanese patients with high tibial osteotomy.

BACKGROUND: To assess responsiveness of the Japanese Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Oxford Knee Score (OKS) in patients undergoing open-wedge HTO to treat knee osteoarthritis and/or osteonecrosis. METHODS: Patients completed a set of questionnaires before HTO surgery (baseline) and 1 year after surgery. The questionnaires comprised the validated Japanese versions of the KOOS, the OKS, and the SF-36v2 and a visual analogue scale (VAS) for local knee pain and general pain. The treating surgeon completed the Japanese Orthopedic Association (JOA) score for osteoarthritic knees. The study included 119 patients aged 64.7 ± 8.3, 116 were followed at 1 year. 90 patients had knee osteoarthritis (OA) solely. 28 patients suffered from both OA and osteonecrosis (ON); one patient had ON only. Responsiveness to change was assessed using the effect size (ES) between the baseline and the 1-year postoperative assessment and standardized response mean. A distribution-based approach was used to determine the minimally detectable change (MDC95) for the KOOS subscales, and the OKS. RESULTS: All instruments demonstrated statistically significant changes between the preoperative assessments and one year after surgery. All changes showed an improvement in score, but the condition-specific measures revealed higher responsiveness than the generic measures. All KOOS subscales, the OKS, the local pain VAS, and the JOA score showed large ESs (ES > 1.24) and SRMs (SRM>1.04). At a 95% confidence level, the respective MDCs were 15.83, 18.94, 15.22, 18.99 and 17.23 for the KOOS-Pain, KOOS-Symptoms, KOOS-ADL, KOOS-Sport/Rec, and KOOS-QOL subscales, respectively. The MDC95 for the OKS was 8.29. CONCLUSIONS: Both, the KOOS and OKS are responsive for use in Japanese-speaking patients with knee osteoarthritis and/or osteonecrosis who are undergoing HTO.

Deep peroneal nerve palsy with isolated lateral compartment syndrome secondary to peroneus longus tear: a report of two cases and a review of the literature.

Drop foot is typically caused by neurologic disease such as lumbar disc herniation, but we report two rare cases of deep peroneal nerve palsy with isolated lateral compartment syndrome secondary to peroneus longus tears. Both patients developed mild pain in the lower legs while playing sport, and were aware of drop foot. As compartment pressures were elevated, fasciotomy was performed immediately, and the tendon of the peroneus longus was completely detached from its proximal origin. The patients were able to return their original sports after 3 months, and clinical examination revealed no hypesthesia or muscle weakness in the deep peroneal nerve area at the time of last follow-up. The common peroneal nerve pierced the deep fascia and lay over the fibular neck, which formed the floor of a short tunnel (the so-called fibular tunnel), then passed the lateral compartment just behind the peroneus longus. The characteristic anatomical situation between the fibular tunnel and peroneus longus might have caused deep peroneal nerve palsy in these two cases after hematoma adjacent to the fibular tunnel increased lateral compartment pressure.

Expression and pathological effects of periostin in human osteoarthritis cartilage.

BACKGROUND: Osteoarthritis (OA) is one of the most common joint diseases in elderly people, however, the underlying mechanism of OA pathogenesis is not completely clear. Periostin, the extracellular protein, has been shown by cDNA array analysis to be highly expressed in OA, but its function is not fully understood. The purpose of this study was to examine the expression and function of periostin in human OA. METHODS: Human cartilage and synovia samples were used for the analysis of periostin expression and function. The human cartilage samples were obtained from the knees of patients undergoing total knee arthroplasty as OA samples and from the femoral bone head of patients with femoral neck fracture as control samples. Quantitative RT-PCR, ELISA, and immunohistochemistry were used for analysis of periostin expression in cartilage and synovia. Human primary chondrocytes isolated from control cartilage were stimulated by periostin, and the alteration of OA related gene expression was examined using quantitative RT-PCR. Immunocytochemistry of p65 was performed for the analysis of nuclear factor kappa B (NFκB) activation. RESULTS: The periostin mRNA was significantly higher in OA cartilage than in control cartilage. Immunohistochemical analysis of periostin showed that the main positive signal was localized in chondrocytes and their periphery matrix near the erosive area, with less immunoreactivity in deeper zones. There was positive correlation between Mankin score and periostin immunoreactivity. The periostin expression was also detected in the fibrotic cartilage and tissue of subchondral bone. In cultured human chondrocytes, periostin induced the expression of interleukin (IL)-6, IL-8, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and nitric oxide synthase-2 (NOS2) in a dose- and time-dependent manner. The activation of NFκB signaling was recognized by the nuclear translocation of p65. Periostin-induced upregulation of these genes was suppressed by NFκB inactivation in chondrocytes. CONCLUSION: Periostin was upregulated in OA cartilage, and it may amplify inflammatory events and accelerate OA pathology.

Analysis of displacement and deformation of the medial meniscus with a horizontal tear using a three-dimensional computer model.

PURPOSE: The displacement and deformation of the knee meniscus significantly affect its roles; however, little is known about the displacement and deformation patterns of a torn medial meniscus. The objective of this study was to evaluate quantitatively the patterns of displacement and deformation in horizontally torn medial menisci during knee flexion. METHODS: Twenty patients with horizontally torn medial menisci underwent three-dimensional (3-D) magnetic resonance imaging at varying degrees of knee flexion, and 3-D computer models of the tibia, tibial articular cartilage, and meniscus were generated. Based on these, the size of the horizontal tear (% tear) was evaluated and defined as the circumferential ratio between the length of the horizontal tear and that of the entire meniscus. The 3-D meniscus models were automatically superimposed over images taken at 0, 20, 40, and 60° of knee flexion by the voxel-based registration method. Meniscal motion and deformation during knee flexion were visualized and quantitatively calculated on the mid-sagittal plane. Correlations between the size of horizontal tear, displacement/deformation of torn menisci, and clinical symptoms were evaluated after conservative treatment for 3 months. RESULTS: The % tear was 35.7 ± 12.5 % (range 13.7-55.5 %). During knee flexion, all torn menisci moved posteriorly, with gradual widening of horizontal and vertical gaps (p < 0.05). A direct correlation was observed between % tear and change in the vertical tear gap during knee flexion (p < 0.05). There was an inverse correlation between Lysholm score and % tear (p < 0.05). CONCLUSION: Medial meniscal horizontal tears widen and deform during knee flexion, and % tear correlates with the change in the vertical gap. Patients with a lower % tear are more capable of performing activities of daily living after conservative treatment. This method may help clarify the cause of pain in patients with medial meniscus tears as well as facilitate the selection of an appropriate treatment plan. LEVEL OF EVIDENCE: Case series, Level IV.

Clonal analysis of synovial fluid stem cells to characterize and identify stable mesenchymal stromal cell/mesenchymal progenitor cell phenotypes in a porcine model: a cell source with enhanced commitment to the chondrogenic lineage.

BACKGROUND AIMS: Previous studies have demonstrated that porcine synovial membrane stem cells can adhere to a cartilage defect in vivo through the use of a tissue-engineered construct approach. To optimize this model, we wanted to compare effectiveness of tissue sources to determine whether porcine synovial fluid, synovial membrane, bone marrow and skin sources replicate our understanding of synovial fluid mesenchymal stromal cells or mesenchymal progenitor cells from humans both at the population level and the single-cell level. Synovial fluid clones were subsequently isolated and characterized to identify cells with a highly characterized optimal phenotype. METHODS: The chondrogenic, osteogenic and adipogenic potentials were assessed in vitro for skin, bone marrow, adipose, synovial fluid and synovial membrane-derived stem cells. Synovial fluid cells then underwent limiting dilution analysis to isolate single clonal populations. These clonal populations were assessed for proliferative and differentiation potential by use of standardized protocols. RESULTS: Porcine-derived cells demonstrated the same relationship between cell sources as that demonstrated previously for humans, suggesting that the pig may be an ideal preclinical animal model. Synovial fluid cells demonstrated the highest chondrogenic potential that was further characterized, demonstrating the existence of a unique clonal phenotype with enhanced chondrogenic potential. CONCLUSIONS: Porcine stem cells demonstrate characteristics similar to those in human-derived mesenchymal stromal cells from the same sources. Synovial fluid-derived stem cells contain an inherent phenotype that may be optimal for cartilage repair. This must be more fully investigated for future use in the in vivo tissue-engineered construct approach in this physiologically relevant preclinical porcine model.

Patellofemoral chondral status after medial patellofemoral ligament reconstruction using second-look arthroscopy in patients with recurrent patellar dislocation.

BACKGROUND: Most patients with recurrent patellar dislocation show cartilage damage in the patellofemoral joint. Medial patellofemoral ligament reconstruction has become one of the most important surgical techniques for treating recurrent patellar dislocation. However, patellofemoral chondral status after this reconstruction has not been elucidated. The purpose of this study was to investigate the effects of medial patellofemoral ligament reconstruction on articular cartilage in the patellofemoral joint by comparing the arthroscopic chondral status at the time of reconstruction with that at second-look arthroscopy. METHODS: Participants in the present study comprised 31 patients (22 females, 9 males; 32 knees) who underwent second-look arthroscopy at a median of 12 months (range 6-40 months) after dual tunnel medial patellofemoral ligament reconstruction using a double-looped autologous semitendinosus tendon graft. Median age at the time of initial surgery was 20 years (range 13-43 years). The patellofemoral joint was divided into six portions, comprising the medial facet of the patella, central ridge, lateral facet of the patella, anterior medial femoral condyle, femoral groove, and anterior lateral femoral condyle. Chondral status in each portion according to the International Cartilage Repair Society classification was retrospectively evaluated at the time of initial surgery and second-look arthroscopy. RESULTS: Before medial patellofemoral ligament reconstruction, chondral lesions were observed in the patellofemoral joint in 31 knees (97%). At the central ridge of the patella, chondral damage was observed in 22 knees (69%) at initial surgery and damaged cartilages showed recovery in 6 knees. No significant difference in the alteration of chondral status was seen for the medial facet, lateral facet of the patella, anterior medial femoral condyle, femoral groove, and anterior lateral femoral condyle. CONCLUSIONS: According to short-term results, the patellofemoral chondral status after medial patellofemoral ligament reconstruction was not altered at second-look arthroscopy in most part of patellofemoral joint. At the central ridge of the patella, significant improvement of the International Cartilage Repair Society grading was observed.

Biologic therapies in stress fractures: Current concepts.

Stress fractures, a common overuse injury in physically active individuals, present a significant challenge for athletes and military personnel. Patients who sustain stress fractures have demanding training regimes where periods of rest and immobilisation have unacceptable negative consequences on sports goals and finances. Aside from being an overuse injury, there are various contributing risk factors that put certain individuals at risk of a stress fracture. The main two being nutritional deficiencies and hormonal variations, which have significant effects on bone metabolism and turnover. Historically, treatment of stress fractures focused on conservative strategies such as rest and immobilisation. Calcium and vitamin D deficiencies have been closely linked to stress fractures and so over time supplementation has also played a role in treatment. With the introduction of biologics into orthopaedics, newer treatment strategies have been applied to accelerate fracture healing and perhaps improve fracture callus quality. If such therapies can reduce time spent away from sport and activity, it would be ideal for treating stress fractures. This article aims to offer insights into the evolving landscape of stress fracture management. It investigates the pre-clinical evidence and available published clinical applications. Though fracture healing is well understood, the role of biologics for fracture healing is still indeterminate. Available literature for the use of biologic therapies in stress fractures are restricted and most reports have used biologics as a supplement to surgical fixation in subjects in studies that lack control groups. Randomised control trials have been proposed and registered by a few groups, with results awaited. Assessing individuals for risk factors, addressing hormonal imbalances and nutritional deficiencies seems like an effective approach to addressing the burden of stress fractures. We await better designed trials and studies to accurately determine the clinical benefit of adding biologics to the management of these injuries.

A novel scaffold-free mesenchymal stem cell-derived tissue engineered construct for articular cartilage restoration - From basic to clinic.

Treatments for articular cartilage injuries are still challenging, due in part to its avascular and aneural surroundings. Since the first report of autologous chondrocyte implantation, cell-based therapies have been extensively studied with a variety of cell sources, including chondrocytes and mesenchymal stem/stromal cells (MSCs). Recently, MSC-based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. Using such cells, we have originally developed a 3-dimensional scaffold-free tissue-engineered construct (TEC) through simple-cell culture methods and demonstrated its feasibility for cartilage repair and regeneration in the first-in-human clinical trial. This review summarizes our novel scaffold-free approaches to use MSC for the restoration of damaged articular cartilage, documenting the progression from basic to clinical studies.

Development of scaffold-free tissue-engineered constructs derived from mesenchymal stem cells with serum-free media for cartilage repair and long-term preservation.

Synovial mesenchymal stem cells (sMSCs) have great potential for cartilage repair, but their therapeutic design to avoid adverse effects associated with unknown factors remains a challenge. In addition, because long-term preservation is indispensable to maintain high quality levels until implantation, it is necessary to reduce their fluctuations. This study aimed to investigate the properties and feasibility of novel scaffold-free tissue-engineered constructs using serum-free media and to develop long-term preservation methods. sMSCs were cultured in serum-free media, seeded at high density in a monolayer, and finally developed as a sheet-like construct called "gMSC1". The properties of frozen gMSC1 (Fro-gMSC1) were compared with those of refrigerated gMSC1 (Ref-gMSC1) and then examined by their profile. Chondrogenic differentiation potential was analyzed by quantitative real-time polymerase chain reaction and quantification of glycosaminoglycan content. Xenografts into the cartilage defect model in rats were evaluated by histological staining. gMSC1 showed nearly similar properties independent of the preservation conditions. The animal experiment demonstrated that the defect could be filled with cartilage-like tissue with good integration to the adjacent tissue, suggesting that gMSC1 was formed and replaced the cartilage. Furthermore, several chondrogenesis-related factors were significantly secreted inside and outside gMSC1. Morphological analysis of Fro-gMSC1 revealed comparable quality levels to those of fresh gMSC1. Thus, if cryopreserved, gMSC1, with no complicated materials or processes, could have sustained cartilage repair capacity. gMSC1 is a prominent candidate in novel clinical practice for cartilage repair, allowing for large quantities to be manufactured at one time and preserved for a long term by freezing. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-024-00637-y.

Correction: Development of scaffold-free tissue-engineered constructs derived from mesenchymal stem cells with serum-free media for cartilage repair and long-term preservation.

[This corrects the article DOI: 10.1007/s10616-024-00637-y.].

Subchondral bone: An emerging target for the treatment of articular surface lesions of the knee.

Purpose: When dealing with the health status of the knee articular surface, the entire osteochondral unit has gained increasing attention, and in particular the subchondral bone, which plays a key role in the integrity of the osteochondral unit. The aim of this article was to discuss the current evidence on the role of the subchondral bone. Methods: Experts from different geographical regions were involved in performing a review on highly discussed topics about the subchondral bone, ranging from its etiopathogenetic role in joint degeneration processes to its prognostic role in chondral and osteochondral defects, up to treatment strategies to address both the subchondral bone and the articular surface. Discussion: Subchondral bone has a central role both from an aetiologic point of view and as a diagnostic tool, and its status was found to be relevant also as a prognostic factor in the follow-up of chondral treatment. Finally, the recognition of its importance in the natural history of these lesions led to consider subchondral bone as a treatment target, with the development of osteochondral scaffolds and procedures to specifically address osteochondral lesions. Conclusion: Subchondral bone plays a central role in articular surface lesions from different points of view. Several aspects still need to be understood, but a growing interest in subchondral bone is to be expected in the upcoming future towards the optimization of joint preservation strategies. Level of Evidence: Level V, expert opinion.