BACKGROUND: In guided bone regeneration (GBR), there are various problems that occur in the bone defect after the wound healing period. This study aimed to investigate the enhancement of the osteogenic ability of the dual scaffold complex and identify the appropriate concentration of growth factors (GF) for new bone formation based on the novel GBR concept that is applying rapid bone forming GFs to the membrane outside of the bone defect. METHODS: Four bone defects with a diameter of 8 mm were formed in the calvaria of New Zealand white rabbits each to perform GBR. Collagen membrane and biphasic calcium phosphate (BCP) were applied to the bone defects with the four different concetration of BMP-2 or FGF-2. After 2, 4, and 8 weeks of healing, histological, histomorphometric, and immunohistochemical analyses were conducted. RESULTS: In the histological analysis, continuous forms of new bones were observed in the upper part of bone defect in the experimental groups, whereas no continuous forms were observed in the control group. In the histomorphometry, The group to which BMP-2 0.5 mg/ml and FGF-2 1.0 mg/ml was applied showed statistically significantly higher new bone formation. Also, the new bone formation according to the healing period was statistically significantly higher at 8 weeks than at 2, 4 weeks. CONCLUSION The novel GBR method in which BMP-2, newly proposed in this study, is applied to the membrane is effective for bone regeneration. In addition, the dual scaffold complex is quantitatively and qualitatively advantageous for bone regeneration and bone maintenance over time.

Cell-based therapies have been used as promising treatments for several untreatable diseases. However, cellbased therapies have side effects such as tumorigenesis and immune responses. To overcome these side effects, therapeutic effects of exosomes have been researched as replacements for cell-based therapies. In addition, exosomes reduced the risk that can be induced by cell-based therapies. Exosomes contain biomolecules such as proteins, lipids, and nucleic acids that play an essential role in cell–cell and cell–matrix interactions during biological processes. Since the introduction of exosomes, those have been proven perpetually as one of the most effective and therapeutic methods for incurable diseases. Much research has been conducted to enhance the properties of exosomes, including immune regulation, tissue repair, and regeneration. However, yield rate of exosomes is the critical obstacle that should be overcome for practical cell-free therapy. Three-dimensional (3D) culture methods are introduced as a breakthrough to get higher production yields of exosomes. For example, hanging drop and microwell were well known 3D culture methods and easy to use without invasiveness. However, these methods have limitation in mass production of exosomes. Therefore, a scaffold, spinner flask, and fiber bioreactor were introduced for mass production of exosomes isolated from various cell types. Furthermore, exosomes treatments derived from 3D cultured cells showed enhanced cell proliferation, angiogenesis, and immunosuppressive properties. This review provides therapeutic applications of exosomes using 3D culture methods.

Background: Many studies on maintaining the condyle in a normal or anatomical position during orthognathic surgery have been conducted to stabilize surgical outcomes and prevent iatrogenic temporomandibular joint complications. The aim of this study is to evaluate the changes in condylar positions after orthognathic surgery using virtual surgical planning via the balanced orthognathic surgery (BOS) system. Methods: Postoperative changes in condylar position were retrospectively evaluated in 22 condyles of 11 patients with skeletal class III malocclusion who underwent orthognathic surgery using virtual surgical planning via the BOS system. The center point coordinates of the condylar head before and after orthognathic surgery were analyzed using voxel-based registration. Results: Changes in the condylar position mainly occurred downward in the y-axis (−1.09 ± 0.62 mm) (P < 0.05). The change in the x-axis (0.02 ± 0.68 mm) and z-axis (0.01 ± 0.48 mm) showed no significant difference between before and after orthognathic surgery. Conclusion These results indicate that the changes in the condylar positions after orthognathic surgery using virtual surgical planning via the BOS system mainly occurred downward in the y-axis, with slight changes in the x- and z-axes. The change in the condylar position after orthognathic surgery using the BOS system is clinically acceptable.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. METHODS: CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. RESULTS: The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. CONCLUSION Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. METHODS: CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. RESULTS: The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. CONCLUSION Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.

Purpose: Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data. Materials and Methods: This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated. Results: Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007). Conclusion Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.

Purpose: To analyze differences in clinical outcomes of arthroscopic anterior cruciate ligament reconstruction between remnant-preserving and non-preserving methods. Methods: International electronical databases PubMed, Embase, and the Cochrane central database from January 1966 to December 2017 were searched for randomized controlled trials (RCTs) and observational studies that compared differences of clinical outcomes of ACL reconstruction with and without remnant preservation. A metaanalysis of these studies was performed to compare clinical outcomes. Subgroup analyses were conducted to evaluate the role of methodological quality in primary meta-analysis estimates. Results: Five RCTsand six observational studies were included in this meta-analysis and subgroup analysis. The remnant-preserving method in arthroscopic ACL reconstruction showed a statistically significant difference compared to the non-preserving method regarding arthrometric evaluation (side-to-side difference). Lachman test, Lysholm scores, and IKDC subjective scores showed statistically minor difference in meta-analysis, but showed no significant difference in subgroup analysis. Remained parameters including pivot shift test, IKDC grades, incidence of cyclops lesion showed no statistically differences in meta-analysis or subgroup analysis. Conclusions: This meta-analysis with subgroup analysis showed that arthroscopic remnant-preserving ACL reconstruction provided statistically significant but limited clinical relevance in terms of arthrometric evaluation. Results of Lachman test, Lysholm scores, and IKDC subjective scores demonstrated statistically minor differences.

Purpose: Our purpose in the current meta-analysis was to compare the functional outcomes in patients who have received single-radius (SR) or multi-radius (MR) femoral components in randomized controlled trials (RCTs) for primary total knee arthroplasty (TKA). The hypothesis was that there would be no statistically significant difference between two groups in terms of functional outcomes. Materials and methods: We searched the international electronic databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to February 2020 for RCTs that compared functional outcomes of SR and MR femoral component designs after primary TKA. We performed a meta-analysis of nine RCTs using the Knee Society Score for the knee (KSS-knee), KSS-function, Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), degree of knee flexion, extension, and complications, including postoperative infection and revision surgery. Results: The meta-analysis revealed no statistically significant differences in all the analyzed variables, including KSSknee, KSS-function, KOOS, OKS, knee flexion, and knee extension. For postoperative complications, no statistically significant differences were detected for femoral component designs in postoperative infection or incidence of revision surgery between the two groups. Conclusions The current meta-analysis of RCTs did not show any statistically significant differences between SR and MR femoral component designs in terms of postoperative functional outcomes. Evaluated outcomes included functional outcome scores, degree of knee flexion, extension, and complications. However, because of the limited clinical evidence of this study owing to the heterogeneity between the included RCTs, a careful approach should be made in order not to arrive at definite conclusions.

Purpose: Our purpose in the current meta-analysis was to compare the functional outcomes in patients who have received single-radius (SR) or multi-radius (MR) femoral components in randomized controlled trials (RCTs) for primary total knee arthroplasty (TKA). The hypothesis was that there would be no statistically significant difference between two groups in terms of functional outcomes. Materials and methods: We searched the international electronic databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to February 2020 for RCTs that compared functional outcomes of SR and MR femoral component designs after primary TKA. We performed a meta-analysis of nine RCTs using the Knee Society Score for the knee (KSS-knee), KSS-function, Knee Injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), degree of knee flexion, extension, and complications, including postoperative infection and revision surgery. Results: The meta-analysis revealed no statistically significant differences in all the analyzed variables, including KSSknee, KSS-function, KOOS, OKS, knee flexion, and knee extension. For postoperative complications, no statistically significant differences were detected for femoral component designs in postoperative infection or incidence of revision surgery between the two groups. Conclusions The current meta-analysis of RCTs did not show any statistically significant differences between SR and MR femoral component designs in terms of postoperative functional outcomes. Evaluated outcomes included functional outcome scores, degree of knee flexion, extension, and complications. However, because of the limited clinical evidence of this study owing to the heterogeneity between the included RCTs, a careful approach should be made in order not to arrive at definite conclusions.

PURPOSE: We investigated the characteristics of lung allocation and outcomes of lung transplant (LTx) according to the Korean urgency status. MATERIALS AND METHODS: LTx registration in the Korean Organ Transplantation Registry (KOTRY) began in 2015. From 2015 to June 2017, 86 patients who received LTx were enrolled in KOTRY. After excluding one patient who received a heart-lung transplant, 85 were included. Subjects were analyzed according to the Korean urgency status. RESULTS: Except for Status 0, urgency status was classified based on partial pressure of oxygen in arterial blood gas analysis and functional status in 52 patients (93%). The wait time for lung allograft was well-stratified by urgency (Status 0, 46.5±59.2 days; Status 1, 104.4±98.2 days; Status 2 or 3, 132.2±118.4 days, p=0.009). Status 0 was associated with increased operative times and higher intraoperative blood transfusion. Status 0 was associated with prolonged extracorporeal membrane oxygenation use, postoperative bleeding, and longer mechanical ventilation after operation. Survival of Status 0 patients seemed worse than that of non-Status 0 patients, although differences were not significant. CONCLUSION: The Korean urgency classification for LTx is determined by using very limited parameters and may not be a true reflection of urgency. Status 0 patients seem to have poor outcomes compared to the other urgency status patients, despite having the highest priority for donor lungs. Further multi-center and nationwide studies are needed to revise the lung allocation system to reflect true urgency and provide the best benefit of lung transplantation.
Allografts ; Blood Gas Analysis ; Blood Transfusion ; Classification ; Extracorporeal Membrane Oxygenation ; Hemorrhage ; Humans ; Lung Transplantation ; Lung ; Operative Time ; Organ Transplantation ; Oxygen ; Partial Pressure ; Respiration, Artificial ; Tissue Donors ; Transplants