Allogenic umbilical cord blood-derived mesenchymal stromal cell implantation was superior to bone marrow aspirate concentrate augmentation for cartilage regeneration despite similar clinical outcomes.

PURPOSE: The aim of this study was to compare clinical and second-look arthroscopic outcomes between bone marrow aspirate concentrate (BMAC) augmentation and human umbilical cord blood-derived mesenchymal stromal cell (hUCB-MSC) implantation in high tibial osteotomy (HTO) for medial compartmental knee osteoarthritis and identify the relationship between articular cartilage regeneration and HTO outcomes. METHODS: A total of 176 patients who underwent HTO combined with a BMAC or hUCB-MSC procedure for medial compartment osteoarthritis (Kellgren-Lawrence grade 3) between June 2014 and September 2018 with a minimum follow-up of 2 years were reviewed. After HTO, multiple holes were drilled at cartilage defect sites of the medial femoral condyle (MFC), and then prepared BMAC or hUCB-MSCs in combination with scaffolds were implanted in the MFC lesions. After propensity score matching based on sex, age, body mass index, and lesion size, 55 patients in each of the BMAC and hUCB-MSC groups were successfully matched. Second-look arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system and Koshino staging system. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Short-Form 36 (SF-36), and Tegner activity scores. RESULTS: At a mean follow-up of 33 months, clinical outcomes including IKDC, KOOS, SF-36, and Tegner activity scores were significantly improved in both groups (p < 0.001); however, there were no differences between the two groups. Second-look arthroscopy showed better healing of regenerated cartilage in the hUCB-MSC group (Grade I [4 cases, 9.1%]; Grade II [30 cases, 68.2%]; Grade III [11 cases, 22.7%]) than in the BMAC group (Grade I [1 case, 2.7%]; Grade II [20 cases, 54.1%]; Grade III [11 cases, 29.7%]; Grade IV [5 cases, 13.5%]) according to the ICRS CRA grading system (p = 0.040). There was no significant intergroup difference in terms of defect coverage based on the Koshino staging system (p = 0.057). Moreover, ICRS CRA grades at second-look arthroscopy were significantly correlated with clinical outcomes (r = - 0.337; p = 0.002). CONCLUSION: There were no significant differences in the clinical outcomes between the two groups. Both treatments provided similar, reliable outcomes in terms of pain relief, functional scores, and quality of life at a mean follow-up of 33 months. However, hUCB-MSC implantation was more effective than BMAC augmentation for articular cartilage regeneration.

Plasma-assisted multiscale topographic scaffolds for soft and hard tissue regeneration.

The design of transplantable scaffolds for tissue regeneration requires gaining precise control of topographical properties. Here, we propose a methodology to fabricate hierarchical multiscale scaffolds with controlled hydrophilic and hydrophobic properties by employing capillary force lithography in combination with plasma modification. Using our method, we fabricated biodegradable biomaterial (i.e., polycaprolactone (PCL))-based nitrogen gas (N-FN) and oxygen gas plasma-assisted flexible multiscale nanotopographic (O-FMN) patches with natural extracellular matrix-like hierarchical structures along with flexible and controlled hydrophilic properties. In response to multiscale nanotopographic and chemically modified surface cues, the proliferation and osteogenic mineralization of cells were significantly promoted. Furthermore, the O-FMN patch enhanced regeneration of the mineralized fibrocartilage tissue of the tendon-bone interface and the calvarial bone tissue in vivo in rat models. Overall, the PCL-based O-FMN patches could accelerate soft- and hard-tissue regeneration. Thus, our proposed methodology was confirmed as an efficient approach for the design and manipulation of scaffolds having a multiscale topography with controlled hydrophilic property.

Allogeneic umbilical cord blood-derived mesenchymal stem cells combined with high tibial osteotomy: a retrospective study on safety and early results.

BACKGROUND: Cartilage repair performed as a single-stage procedure is an important advancement in the treatment of full-thickness cartilage injury and has potential for widespread clinical use. PURPOSE: To investigate the short-term outcomes and cartilage regeneration after implantation of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in patients who received high tibial osteotomy (HTO) for symptomatic medial knee osteoarthritis. METHODS: Patients underwent treatment of full-thickness chondral injury in the osteoarthritic knee with HTO and implantation of hUCB-MSCs and were followed prospectively for a minimum of one year. Ninety-three patients were followed for a mean 1.7 years (range, 1.0-3.5). Median cartilage lesion size was 6.5 cm2 (range, 2.0-12.8). Clinical outcomes were examined with patient-reported scoring instruments that consisted of the International Knee Documentation Committee (IKDC) subjective score, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, Knee Society Score (KSS), and Hospital for Special Surgery (HSS) score. Cartilage regeneration was evaluated using the International Cartilage Repair Society (ICRS) cartilage repair assessment grading (CRA) system and the Koshino regeneration staging system in 49 patients who underwent second look arthroscopic assessment when their HTO plates were removed. RESULTS: At final follow-up, the median IKDC subjective score had significantly improved from 39.0 to 71.3; the WOMAC score from 44.5 to 11.0; the KSS pain and function scores from 29.8 to 43.2 and 61.0 to 81.2, respectively; and the HSS from 61.6 to 82.7 (p < 0.05). Pre-operative examination showed ICRS grade IV cartilage injury in all knees, and cartilage regeneration at 2nd look arthroscopy showed improvements (8.2% of patients improved to ICRS grade I, 69.3% to grade II, and 22.5% to grade III). Moreover, Koshino stage was B in 24.5% and C in 75.5% of patients (p < 0.05). CONCLUSION: Allogeneic hUCB-MSC implantation combined with HTO for medial knee osteoarthritis was safe and showed signs of cartilage status improvement. Furthermore, randomized controlled studies with a control group are necessary to determine the real effectiveness and indications of this new combined procedure for patients with osteoarthritis.

The Influence of Preoperative Tibial Bone Marrow Edema on Outcomes After Medial Opening-Wedge High Tibial Osteotomy.

BACKGROUND: The relationship between preoperative subchondral bone marrow edema (BME) in the osteoarthritic knee and pain has been established. However, little is known about the influence of preoperative BME on outcomes after medial opening-wedge high tibial osteotomy (MOHTO). The purpose of this study was to clarify the association between preoperative BME severity and clinical outcomes after MOHTO at intermediate follow-up. METHODS: We reviewed the cases of 105 consecutive patients who underwent MOHTO for osteoarthritis of the knee with preoperative subchondral BME in the medial aspect of the tibia between January 2005 and December 2015. BME was evaluated using magnetic resonance imaging (MRI). The sizes of the BME lesions were determined on the basis of the maximum diameter and were classified as small (<1 cm), medium (<2 cm), large (<4 cm), or very large (diffuse; >4 cm). Associations between preoperative BME severity and postoperative outcomes at a mean follow-up of 6.2 years (range, 2.0 to 14.3 years) were evaluated according to a Spearman correlation matrix with each reviewer's grades. Functional outcomes were assessed using the Hospital for Special Surgery (HSS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Society Score (KSS), and Short Form-12 (SF-12) questionnaire. Survival rate and complications were also evaluated. RESULTS: The degree of preoperative BME was not significantly correlated with postoperative outcomes (p > 0.05). There were significant improvements between the preoperative and latest follow-up assessments in all functional outcome categories (p < 0.001). Patients demonstrated marked improvements with respect to pain, function, and quality of life. The overall survival rate was 95.2%, with a mean follow-up of 6.2 years. Six major complications were identified in 5.7% of the patients, and these resulted in 5 patients (4.8%) who had conversion to total knee arthroplasty. CONCLUSIONS: We did not find any correlation between preoperative subchondral BME severity and postoperative outcomes. MOHTO showed good functional outcomes, a low major complication rate, and an excellent survival rate with a mean follow-up of 6.2 years, regardless of the degree of preoperative BME. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Genome-Wide Transcriptome Analysis of Rice Seedlings after Seed Dressing with Paenibacillus yonginensis DCY84T and Silicon.

Plant-growth-promoting bacteria (PGPB) are beneficial microorganisms that can also protect against disease and environmental stress. Silicon (Si) is the second most abundant element in soil, and is known to increase plant growth, grain yield, resistance to biotic stress, and tolerance to abiotic stress. Combined treatment of PGPB and Si has been shown to further enhance plant growth and crop yield. To determine the global effects of the PGPB and Si on rice growth, we compared rice plants treated with Paenibacillus yonginensis DCY84T (DCY84T) and Si with untreated rice. To identify the genes that respond to DCY84T+Si treatment in rice, we performed an RNA-Seq transcriptome analysis by sampling treated and untreated roots on a weekly basis for three weeks. Overall, 576 genes were upregulated, and 394 genes were downregulated in treated roots, using threshold fold-changes of at least 2 (log2) and p-values < 0.05. Gene ontology analysis showed that phenylpropanoids and the L-phenylalanine metabolic process were prominent in the upregulated genes. In a metabolic overview analysis using the MapMan toolkit, pathways involving phenylpropanoids and ethylene were strongly associated with upregulated genes. The functions of seven upregulated genes were identified as being associated with drought stress through a literature search, and a stress experiment confirmed that plants treated with DCY84T+Si exhibited greater drought tolerance than the untreated control plants. Furthermore, the predicted protein-protein interaction network analysis associated with DCY84T+ Si suggests mechanisms underlying growth promotion and stress tolerance.