Search

FNU Romaniyanto,1– 3 Ferdiansyah Mahyudin,4,5 Cita Rosita Sigit Prakoeswa,5,6 Hari Basuki Notobroto,7 Damayanti Tinduh,5,8 Ryan Ausrin,2,3 Fedik Abdul Rantam,9,10 Heri Suroto,4,5 Dwikora Novembri Utomo,4,5 Sholahuddin Rhatomy11 1Doctoral Program, Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 2Department of Orthopedic and Traumatology, Prof. Dr. R. Soerharso Orthopedic Hospital, Surakarta, Indonesia; 3Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia; 4Department of Orthopedic and Traumatology, Dr. Soetomo General Hospital, Surabaya, Indonesia; 5Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 6Department of Dermatology and Venereology, Dr. Soetomo General Hospital, Surabaya, Indonesia; 7Faculty of Public Health, Airlangga University, Surabaya, Indonesia; 8Department of Physical Medicine and Medical Rehabilitation, Dr. Soetomo General Hospital, Surabaya, Indonesia; 9Virology and Immunology Laboratory, Microbiology Department, Faculty of Veterinary Medicine, Airlangga University, Surabaya, Indonesia; 10Stem Cell Research and Development Center, Airlangga University, Surabaya, Indonesia; 11Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, IndonesiaCorrespondence: Sholahuddin Rhatomy, Department of Orthopaedics and Traumatology, Dr. Soeradji Tirtonegoro General Hospital, Klaten, Indonesia, Tel +62 272-321163, Fax +62 272-321104, Email doktergustomrhatomy@yahoo.com; sholahuddin.rhatomy@mail.ugm.ac.idAbstract: The intervertebral disc (IVD) is an important structure in the human body because it functions as a weight-bearing. This structure undergoes a process of degeneration like the rest of the body and this process is known as intervertebral disc degeneration (IDD) which is the most common cause of low back pain (LBP). The current common management, either conservative or surgical, is pain-relieving and has not been able to restore degenerated disc optimally. Changes in the IVD microenvironment in IDD conditions make it difficult for the regeneration process to occur. Research to reverse the degeneration process continues to develop, one of them is the use of adipose-derived stem cells (ASCs). ASCs is superior due to the ability to differentiate into several other cells such as adipocytes, chondrocytes, and osteoblasts, it also has ability to act as immunomodulators by stimulating the migration of immune cells to damaged tissues. ASCs becomes a good choice because it is easy to obtain, low donor site morbidity, high proliferation rate, and excellent differentiation abilities. Research on the optimal preparation process for ASCs and their application to various disorders continues to advanced. This study aims to review the potential use of ASCs for regeneration of intervertebral disc degeneration.Keywords: adipose-derived stem cells, stem cell, intervertebral disc, intervertebral disc degeneration, low back pain

Tito Sumarwoto,1,2 Heri Suroto,3 Ferdiansyah Mahyudin,3 Dwikora Novembri Utomo,3 FNU Romaniyanto,2 Andhi Prijosedjati,2 Hari Basuki Notobroto,4 Damayanti Tinduh,5 Cita Rosita Sigit Prakoeswa,6 Fedik Abdul Rantam,7,8 Sholahuddin Rhatomy9,10 1Doctoral Program, Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 2Department of Orthopaedics and Traumatology, Prof Soeharso Orthopaedic Hospital/Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia; 3Department of Orthopaedics and Traumatology, Dr. Soetomo General Hospital/Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 4Faculty of Public Health, Airlangga University, Surabaya, Indonesia; 5Physical Medicine and Rehabilitation Department, Universitas Airlangga, Surabaya, Indonesia; 6Department of Dermatology and Venereology, Dr. Soetomo General Hospital/Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 7Virology and Immunology Laboratory, Microbiology Department, Faculty of Veterinary Medicine, Airlangga University, Surabaya, Indonesia; 8Stem Cell Research and Development Center, Airlangga University, Surabaya, Indonesia; 9Department of Orthopaedics and Traumatology, Dr. Soeradji Tirtonegoro General Hospital, Klaten, Indonesia; 10Faculty of medicine, public health and nursing, Universitas Gadjah Mada, Yogyakarta, IndonesiaCorrespondence: Sholahuddin Rhatomy, Department of Orthopaedics and Traumatology, Dr. Soeradji Tirtonegoro General Hospital, Klaten, Indonesia, Email doktergustomrhatomy@yahoo.comBackground: Brachial plexus injury is an advanced and devastating neurological injury, for which both nerve surgery and tendon transfers sometimes remain insufficient in restoring normal movement. Stem cell therapy may be applicable to rescue the injured motor neurons from degeneration which potentially improves muscle strength.Study Design: Systematic Review; Level of evidence V.Data Sources: A systematic literature search was conducted on PubMed (MEDLINE), EMBASE, the Cochrane Library, and Scopus using the terms (“stem cell”) AND (“brachial plexus”) as search keywords.Methods: The process of study selection was summarized by PRISMA flow diagram. The study included in vivo and in vitro studies with English language, humans or animals with some brachial plexus injuries, interventions, some applications of stem cells to the groups of study, with functional, biomechanical, or safety outcomes.Results: In total, there were 199 studies identified from the literature sources where 75 articles were qualified for forward evaluation following selecting the titles and abstracts. Ten studies were finally included in this systematic review after full-text assessment. Stem cells can produce neurotrophic factors in vitro and in vivo in rats, and their level was increased after injury. Electrophysiological measurement showed that the intervention group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than the model group. Application of bone marrow stem cells (BMSCs) showed an elevation in the numbers of axons and density of myelinated fibers, the density of nerve fibers, the diameter of regenerating axons, and a decrease in axonal degeneration. A study in humans indicated an improvement of the movements in a patient with traumatic total BPI after injection of Ad-MSC. It is associated with increased muscle mass and sensory recovery and also suggested that mononuclear cell injection enhances muscle regeneration and reinnervation in the partly denervated muscle of brachial plexus injury. Various muscle groups had obtained strength together with restoration, the muscle strength attained after the previous transplantation were preserved. The results of this review support stem cell treatment in brachial plexus injury.Conclusion: This review provides evidence of the positive effects of stem cell treatment in brachial plexus injury.Keywords: stem cell, brachial plexus injury, promising therapy

Romaniyanto,1– 3 Ferdiansyah Mahyudin,4,5 Cita Rosita Sigit Prakoeswa,5,6 Hari Basuki Notobroto,7 Damayanti Tinduh,5,8 Ryan Ausrin,2,3 Fedik Abdul Rantam,9,10 Heri Suroto,4,5 Dwikora Novembri Utomo,4,5 Sholahuddin Rhatomy11,12 1Doctoral Program, Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 2Department of Orthopedic and Traumatology, Prof. Dr. R. Soeharso Orthopedic Hospital, Surakarta, Indonesia; 3Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia; 4Department of Orthopedic and Traumatology, Dr. Soetomo General Hospital, Surabaya, Indonesia; 5Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 6Department of Dermatology and Venereology, Dr. Soetomo General Hospital, Surabaya, Indonesia; 7Faculty of Public Health, Airlangga University, Surabaya, Indonesia; 8Department of Physical Medicine and Medical Rehabilitation, Dr. Soetomo General Hospital, Surabaya, Indonesia; 9Virology and Immunology Laboratory, Microbiology Department, Faculty of Veterinary Medicine, Airlangga University, Surabaya, Indonesia; 10Stem Cell Research and Development Center, Airlangga University, Surabaya, Indonesia; 11Department of Orthopaedics and Traumatology, Dr. Soeradji Tirtonegoro General Hospital, Klaten, Indonesia; 12Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, IndonesiaCorrespondence: Sholahuddin Rhatomy, Department of Orthopaedics and Traumatology, Dr. Soeradji Tirtonegoro General Hospital, Klaten, Indonesia, Email sholahuddin.rhatomy@ugm.ac.idBackground: This study aimed to investigate the effects of hypoxia and normoxia preconditioning in rabbit intervertebral disc-derived stem cells (IVDSCs) and discus-derived conditioned medium (DD-CM)/secretomes in vitro. Transforming growth factor (TGF)-β 1, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) have a role in the proliferation, development, differentiation, and migration of MSCs.Materials and Methods: Intervertebral discs were isolated from rabbit and incubated in normoxia and hypoxia 1%, 3%, and 5% (hypoxia groups) condition. Cell counting was performed after 24 hours of manipulation, then analyzed using one-way ANOVA. TGF-β 1, PDGF, FGF, and VEGF were measured using the ELISA.Results: The highest number of cells was in the hypoxia 3% preconditioning compared to the normoxia, hypoxia 1%, and hypoxia 5% groups. Hypoxia 3% also had the highest increase in PDGF protein production compared to normoxia, with hypoxia 1% and 5%. Among hypoxia groups, the highest secretions of VEGF and FGF proteins were in the hypoxia 3% group. Based on TGF-β 1 protein measurement, the hypoxia 1% group was the highest increase in this protein compared to other groups.Conclusion: Oxygen level in hypoxia preconditioning has a role in the preparation of IVDSCs and secretome preparation in vitro. The highest cell numbers were found in the treatment group with 3% hypoxia, and 3% hypoxia was significantly related to support IVDSCs preparation. Preconditioning with 3% hypoxia had higher PDGF and VEGF levels than other hypoxia groups.Keywords: intervertebral disc-derived stem cells, secretomes, growth factors, hypoxia, normoxia

Ferdiansyah Mahyudin,1 Fachrizal Arfani Prawiragara,1 Mouli Edward,1 Dwikora Novembri Utomo,1 Mohammad Hardian Basuki,1 Yunus Abdul Bari,1 Alexander Patera Nugraha,2 Fedik Abdul Rantam3 1Orthopedic and Traumatology Department, Faculty of Medicine, Dr Soetomo General Hospital, Airlangga University, Surabaya, Indonesia; 2Orthodontics Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia; 3Laboratory of Virology and Immunology, Microbiology Department, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, IndonesiaCorrespondence: Ferdiansyah Mahyudin Email ferdiansyah@fk.unair.ac.idIntroduction: Peripheral blood mononuclear cells (PBMCs) sensitized with mesenchymal stem cells (MSCs) secretome and/or colony stimulating factor-2 (CSF-2) as an immunotherapy candidate may escalate osteosarcoma stem cells (OS-SCs) apoptosis. This study aimed to investigate the escalation of osteosarcoma stem cells’ apoptosis after the co-cultivation with PBMCs sensitized by MSCs secretome with/or CSF-2 and it was completed by analyzing the level of serum tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) and tumor necrosis factor-α (TNF-α) level, annexin V binding, caspase-3 and caspase-8 expression in vitro.Methods: OS-SCs were derived from a single human osteosarcoma sample with its high grade and osteoblastic essential clinical characteristics obtained from a biopsy before the chemotherapy treatment. They were then isolated and cultured confirmed by the cluster of differentiation-133 (FITC) by applying immunofluorescence analysis with fluorescein isothiocyanate (FITC) labeled. MSCs secretome was obtained with cells extracted from the bone marrow of a healthy patient. Furthermore, enzyme linked immunosorbent assay (ELISA) was utilized to analyze sTRAIL and TNF-α level in each group. The expression of caspase-3, caspase-8, and annexin V assay in each group was examined by applying the immunofluorescence labeled with FITC. The comparison analysis between treatment groups and the control group was performed by utilizing the analysis of variance (ANOVA) and continued with Tukey Honest Significant Difference (HSD) (p< 0.05).Results: There was a significant difference in the upregulation of sTRAIL and TNF-α level indicated by the increased annexin V, caspase-3, and caspase-8 expression binding between groups (p< 0.05).Conclusion: MSCs Secretome and CSF-2 could significantly increase the activity of PBMCs through the improvement of sTRAIL and TNF-α levels which could lead to the escalation of OS-SCs apoptosis through an enhanced expression of caspase 3, caspase 8 and annexin V binding in vitro.Keywords: cancer, caspase, osteosarcoma, peripheral blood mononuclear cells, mesenchymal stem cells, tumor necrosis factor

High-grade osteosarcoma, a primary malignant bone tumour, is experiencing a global increase in reported incidence with varied prevalence. Despite advances in management, which include surgery and neoadjuvant chemotherapy often an unsatisfactory outcome is found due to poor or heterogeneous response to chemotherapy. Our study delved into chemotherapy responses in osteosarcoma patients and associated molecular expressions, focusing on CD95 receptor (CD95R), interferon (IFN)-γ, catalase, heat-shock protein (Hsp)70, and vascular endothelial growth factor (VEGF). Employing immunohistochemistry and Huvos grading of post-chemo specimens, we analysed formalin-fixed paraffin-embedded (FFPE) osteosarcoma tissue of resected post-chemotherapy specimens from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia (DSGAH), spanning from 2016 to 2020. Results revealed varied responses (poor 40.38%, moderate 48.08%, good 11.54%) and distinct patterns in CD95R, IFN-γ, catalase, Hsp70, and VEGF expression. Significant differences among response groups were observed in CD95R and IFN-γ expression in tumour-infiltrating lymphocytes. The trend of diminishing CD95R expression from poor to good responses, accompanied by an increase in IFN-γ, implied a reduction in the count of viable osteosarcoma cells with the progression of Huvos grading. Catalase expression in osteosarcoma cells was consistently elevated in the poor response group, while Hsp70 expression was highest. VEGF expression in macrophages was significantly higher in the good response group. In conclusion, this study enhances our understanding of immune-chemotherapy interactions in osteosarcoma and identifies potential biomarkers for targeted interventions., (© 2024. The Author(s).)

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting., Competing Interests: A. Puri is a member of the editorial board of The Bone & Joint Journal. P. Ruggieri reports consulting fees from Exactech and Stryker, unrelated to this study. M. T. Houdek reports consulting fees from Link Orthopedics, unrelated to this study. E. Botello reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Zimmer Biomet, all of which are unrelated to this study. G. V. Morris reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Implantcast, all of which are unrelated to this study., (© 2024 Jeys et al.)

Bone implants are important in the recovery of fractures and degenerative diseases. Although many implants have been marketed, study on Indonesian-made plates is still limited. The aim of this study was to assess the patients' functional and radiological improvements and biomechanical and chemical changes of Indonesian-made plates used in long bone fractures. retrospective study was conducted at Semen Gresik Hospital, Gresik, Indonesia. This study included adult patients with long bone fractures who had surgeries with Indonesian plates. Functional improvement (assessed using disabilities of arm, shoulder, and hand (DASH) or lower extremity functional scale (LEFS)) and radiological data (assessed using radiographic union score (RUS)) were assessed in week 4 and month 6, 12, and 15 after surgery. Biomechanical changes (hardness and roughness test) and chemical analysis were assessed after 15 months of use. The normality of the data was tested with Shapiro-Wilk while data analysis was conducted using paired Student t-test or Friedman test as appropriate with type of data. Our data indicated that the DASH and LEFS functional scores had significant improvement over the follow-ups indicating functional recovery. RUS scores also improved over time, indicating a good healing process. Hardness tests on post-surgery implants showed a decrease in hardness of 7.3% and an increase of 3.3% in roughness. Chemical analysis showed a reduction in chemical levels in the implant of 7.8%, indicating durability and minimal toxicity. This study highlights that Indonesian implants have been proven safe to use in fractures. Further examinations with a larger sample and a longer duration of monitoring are recommended for stronger validity., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 by the authors.)

Bone grafting has emerged as a key solution in bone defect management such as allograft, graft of bone from another individual. However, bone allografts usually undergo rigorous preparation to eliminate immune-triggering elements. The deep-freezing methods may delay graft use, while cryopreservation using liquid nitrogen allows rapid freezing but may alter graft characteristics. The aim of this study was to investigate the post-preservation changes in bone allograft characteristics and to compare the effectiveness of deep-freezing and liquid nitrogen methods using animal model. An experimental study using a post-test only control group design was conducted. Fresh-frozen femoral cortical bone was obtained from male New Zealand white rabbits. Preservation by deep-freezing involved placing bone samples in a -80°C freezer for 30 days. For liquid nitrogen preservation, bone grafts were immersed in liquid nitrogen for 20 min, followed by a 15-min rest at room temperature and a final immersion in 0.9% sodium chloride at 30°C for 15 min. Bone samples then underwent evaluation of cell viability, compression, and bending tests. Cell viability test employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and the compression and bending tests used the Universal Testing Machine (UTM). Independent Student t-test or Mann-Whitney U test were used to compare the methods as appropriate. Our study found that the use of deep-freezing and liquid nitrogen resulted in similar outcomes for cell viability, compression, and bending tests, with p -values of 0.302, 0.745, and 0.512, respectively. Further exploration with larger sample sizes may help to optimize the methods for specific applications., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 by the authors.)

The process of decellularization is crucial for producing a substitute for the absent tracheal segment, and the choice of agents and methods significantly influences the outcomes. This paper aims to systematically review the efficacy of diverse tracheal decellularization agents and methods using the PRISMA flowchart. Inclusion criteria encompassed experimental studies published between 2018 and 2023, written in English, and detailing outcomes related to histopathological anatomy, DNA quantification, ECM evaluation, and biomechanical characteristics. Exclusion criteria involved studies related to 3D printing, biomaterials, and partial decellularization. A comprehensive search on PubMed, NCBI, and ScienceDirect yielded 17 relevant literatures. The integration of various agents and methods has proven effective in the process of tracheal decellularization, highlighting the distinct advantages and drawbacks associated with each agent and method., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Dhihintia Jiwangga et al.)

Currently, a tissue-engineered trachea has been popularly used as a biological graft for tracheal replacement in severe respiratory diseases. In the development of tissue-engineered tracheal scaffolds, in vitro studies play a crucial role in allowing researchers to evaluate the efficacy and safety of scaffold designs and fabrication techniques before progressing to in vivo or clinical trials. This research involved the decellularization of goat trachea using SDS, H 2 O 2 , and their combinations. Various quantitative and qualitative assessments were performed, including histological analysis, immunohistochemistry, and biomechanical testing. Hematoxylin and eosin staining evaluated the cellular content, while safranin O-fast green and Masson's trichrome staining assessed glycosaminoglycan content and collagen distribution, respectively. The immunohistochemical analysis focused on detecting MHC-1 antigen presence. Tensile strength measurements were conducted to evaluate the biomechanical properties of the decellularized scaffolds. The results demonstrated that the combination of SDS and H 2 O 2 for goat tracheal decellularization yielded scaffolds with minimal cellular remnants, low toxicity, preserved ECM, and high tensile strength and elasticity. This method holds promise for developing functional tracheal scaffolds to address severe respiratory diseases effectively., Competing Interests: The authors declare that they do not have conflicts of interest., (Copyright © 2024 Dhihintia Jiwangga et al.)

Background: Periodontal disease is common in both developed and developing countries and affects around 20-50% of the global population, especially in adolescents, adults and the elderly is a public health problem. ADMSCs have the advantage of regenerating damaged tissue with high quality. DDM in the form of slices can improve healing in the mandibular sockets of molar teeth. The combination of ADMSC-DDM is expected to accelerate bone regeneration., Objectives: To analyze the combination of ADMSCs-DDM at increasing bone marker expression in periodontitis rats., Methods: This research is experimental with a randomized control group post-test-only design. A total of 50 male Wistar rats were divided into four groups: 1) normal group (K); 2) CP model (K + ); 3) CP model and treated with DDM scaffold therapy (K(s)); 4) CP model and treated with ADMSCs-DDM combination therapy (K(sc)). Making a CP model with injected LPS P. gingivalis into interproximal gingiva of the right first and second lower molars. The in vivo research stage was the implantation of the DDM scaffold and the ADMSCs-DDM combination in the rat periodontal pocket. Rats were euthanized on days 7, 14, and 28, and immunohistochemistry of STRO-1, RUNX-2, OSX, COL-I, and OCN was performed. DDM scaffolds are made in 10%, 50% and 100% concentrations for MTT testing. Statistical results were analyzed with Kruskal-Wallis and Mann-Whitney tests., Results: The results of the MTT scaffold DDM were significant in the 10%, 50%, and 100% dilution groups (p < 0.05). The results showed there was a substantial difference in the expression of STRO-1 between the study groups (p < 0.05). The (K(sc)) was significantly higher than the (K) in RUNX-2 expression (p < 0.05). OSX expression showed significant results between study groups (p < 0.05). The expression of OCN and COL-I showed a significant difference in all study groups on day 28, where the (K(sc)) was higher than the (K) (p < 0.05)., Conclusions: Administration of the ADMSCs-DDM combination can accelerate alveolar bone regeneration on day 28. There is a mechanism of alveolar bone regeneration through the STRO-1, RUNX-2, OSX, and the COL-I pathway in periodontitis models., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

High tibial osteotomy is a reliable procedure for the correction of knee varus deformity. An opening-wedge high tibial osteotomy (OW-HTO) is the most popular technique. The results of the bone defect after opening the wedge needed special treatment to ensure bone healing. This study aims to evaluate the use of bovine-derived hydroxyapatite graft for defect filling after OW-HTO., Methods: A retrospective study was performed on all patients who received OW-HTO at Prof. Dr R. Soeharso Orthopaedic Hospital from November 2019 to December 2022. A total of 21 patients (24 knees) were included in this study. Clinical dan radiological evaluation was performed on all patients preoperative and postoperatively. The mean of the follow-up period was 12.6 months with a minimum of 4 months follow-up., Results: Primary medial uni-compartment knee osteoarthritis was the most common diagnosis, with 17 of 24 cases (70.8%). Mechanical axis deviation was changed from 31 mm medial deviation (range: 8-52 mm) to 0.45 mm medial deviation (range: 13 - (-8) mm). The anatomic tibiofemoral angle was corrected from a preoperative mean of 4.7 ° of varus to a mean of 5.8 ° of valgus postoperatively. Bone defect height was mean 15.9 mm with a range of 10-23 mm. Bone defect width was mean 46.7 mm (range: 34-60 mm). Hydroxyapatite graft integration with the host bone was found in all patients during the final follow-up period., Conclusions: Bovine-derived hydroxyapatite graft is a safe and effective material for bone defect filling in OW-HTO procedures with a high bone union rate., Competing Interests: The authors declare that they have no financial conflict of interest with regard to the content of this report., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The hypoxic condition is a physiological norm for various stem cells. The natural microenvironment contains lower oxygen pressures. Recent studies reported significant increases in the cultured cells' proliferation in the presence of a low oxygen pressure., Objective: This study aimed to investigate the optimum oxygen level for rabbit cruciate ligament fibroblast cells culture and Ligament Derived Conditioned Medium/LD-CM (Secretome) preparation in vitro., Materials and Methods: Fibroblasts were isolated from the cruciate ligament of the rabbit's knee. Cultured of rabbit cruciate ligament Fibroblast Cells (fifth passage) were assigned to the slight (5% O 2 ), middle (3% O 2 ), and severe hypoxia (1% O 2 ) groups and the normoxia (21% O 2 ) group. Measurement of growth factors: TGF-β1, PDGF, FGF, and VEGF in LD-CM (Secretome) used an enzyme-linked immunosorbent assay., Results: The highest number of cultured cells were in the 5% O 2 group compared to the normoxia, 1 and 3% groups. The hypoxia 5% group also had increased productions of PDGF, FGF, and VEGF proteins in LD-CM (secretome) compared to the 1, 3%, and normoxia groups. TGF-β1 production was slightly higher in the 3 group than the 5% group., Conclusion: The hypoxic precondition of 5% oxygen was the optimum condition for ligament culture and ligament derived conditioned medium (secretome) preparation in vitro., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Intervertebral disk degeneration (IDD) is a chronic condition brought on by various factors and mechanisms that have been linked to many deaths and illnesses. The causes of IDD involve multiple processes, including genetics, stress, cellular aging, and changes in nutrition due to the limited blood supply. Animal models play a crucial role in biomedical research and the selection of these models is based on many considerations, including the need for similarities in structure and function with humans. This is important because the etiology and pathogenesis of IDD are complex. Finding the right animal model is not an easy task. In addition to having similarities to humans, these models should also be reliable, reproducible, cost-effective, and easy to maintain. One common method of inducing IDD in animal models is needle puncture. This method is less invasive and time-consuming compared to other methods and allows for precise control over the extent and location of the injury., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The preconditioning hypoxia for stem cells is a strategy to achieve effective conditions for cell therapy, indicate increased expression of regenerative genes in stem cell therapy, and enhance the secretion of bioactive factors and therapeutic potential of their cultured secretome., Objectives: This study aims to explore the response of Schwann-like cells derived from adipose-derived mesenchymal stem cells (SLCs) and Schwann cells rat sciatic nerve-derived stem cells (SCs) with their secretomes under normoxic and hypoxic conditions in vitro ., Material and Methods: SLCs and SCs were isolated from the adipose tissue and the sciatic nerve of the adult white male rat strain Wistar. Cells were incubated in 21% O 2 (normoxic group) and 1%, 3%, and 5% O 2 (hypoxic group) conditions. Concentration values of transforming growth factor-β (TGF-β), basic Fibroblast Growth factor (bFGF), brain-derived neurotrophic factor, glial-derived neurotrophic factor, vascular endothelial growth factor, and nerve growth factor were detected and calculated utilizing an enzyme-linked immunosorbent assay, and the growth curve was described., Results: SLCs and SCs indicated positive expression for mesenchymal markers and negative expression for hematopoietic markers. Normoxic conditions SLCs and SCs showed elongated and flattened morphology. Under hypoxic conditions, SLCs and SCs showed a classic fibroblast-like morphology. Hypoxia 1% gave the highest concentration in TGF-β and bFGF from the SLCs group and TGF-β, bFGF, brain-derived neurotrophic factor, and vascular endothelial growth factor from the SCs group. No significant differences in concentration of growth factors between the SLCs group compared to SCs group in all oxygen groups., Conclusions: Preconditioning hypoxia has an effect on the composing of SLCs, SCs, and their secretomes in vitro ; no significant differences in concentration of growth factors between the SLCs group compared with the SCs group in all oxygen groups., Competing Interests: No conflict of interest for all of authors regarding this study., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The COVID-19 pandemic had greatly and negatively impacted health services including the management of bone and soft tissue sarcoma. As disease progression is time-sensitive, decision taken by the oncology orthopedic surgeon on performing surgical treatment determines the patient outcome. On the other hand, as the world tried to control the spread of COVID-19 infection, treatment re-prioritization based on urgency level had to be done which consequently affect treatment provision for sarcoma patients. Patient and clinician's concern regarding the outbreak have also inflicted on treatment decision making. A systematic review was thought to be necessary to summarize the changes seen in managing primary malignant bone and soft tissue tumors., Methods: We performed this systematic review in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. The review protocol had been registered on PROSPERO with submission number CRD42022329430. We included studies which reported primary malignant tumor diagnosis and its surgical intervention from March 11th, 2020 onwards. The main outcome is to report changes implemented by different centers around the world in managing primary malignant bone tumors surgically in response to the pandemic. Three electronic medical databases were scoured and by applying eligibility criteria. Individual authors evaluated the articles' quality and risk of bias using the Newcastle-Ottawa Quality Assessment Scale other instruments developed by JBI of the University of Adelaide. The overall quality assessment of this systematic review was self-evaluated using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Checklist., Results: There were 26 studies included in the review with various study designs, conveyed in almost all continents. The outcomes from this review are change in surgery time, change in surgery type, and change in surgery indication in patients with primary bone and soft tissue sarcoma. Surgery timing has been experiencing delay since the pandemic occurred, including delay in the multidisciplinary forum, which were all related to lockdown regulations and travel restrictions. For surgery type, limb amputation was preferred compared to limb-salvage procedures due to shorter duration and simpler reconstruction with better control of malignancy. Meanwhile, the indications for surgical management are still based on the patient's demographics and disease stages. However, some would stall surgery regardless of malignancy infiltration and fracture risks which are indication for amputation. As expected, our meta-analysis showed higher post-surgical mortality in patients with malignant bone and soft tissue sarcoma during the COVID-19 pandemic with odds ratio of 1.14., Conclusion: Surgical management of patients with primary bone and soft tissue sarcoma has seriously been affected due to adjustments to the COVID-19 pandemic. Other than institutional restrictions to contain the infection, patient and clinician's decisions to postpone treatment due to COVID-19 transmission concern were also impactful in treatment course. Delay in surgery timing has caused higher risk of worse surgical outcome during the pandemic, which is aggravated if the patient is infected by COVID-19 as well. As we transition into a post-COVID-19 pandemic period, we expect patients to be more lenient in returning for their treatment but by then disease progression might have taken place, resulting in worse overall prognosis. Limitation to this study were few assumptions made in the synthesis of numerical data and meta-analysis only for changes in surgery time outcome and lack of intervention studies included., Competing Interests: All author declare that they have no conflict of interest., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Intervertebral disc degeneration is a natural process of aging. It can cause physical, psychological, and socioeconomic impact due to the decreasing function of the spine and pain manifestation. Conservative and surgical treatment to correct symptoms and structural anomalies does not fully recover the degenerated disc. Several therapeutic approaches have been developed to improve the clinical result and patient's quality of life. This paper aims to review previous studies that discussed potential novel approach in order to make effective degenerated disc restoration. We tried to briefly describe IVD, IDD, also review several promising current therapeutic approaches for degenerated disc treatment, including its relevance to the degeneration process and limitation to be applied in a clinical setting. There are generally four current therapeutic approaches that we reviewed; growth factors, small molecules, gene therapy, and stem cells. These new approaches aim to not only correct the symptoms but also restore and delay the degeneration process., (© 2022 The Authors.)

The most widely used biomaterials in the treatment of massive bone defects are allograft bone or metal implants. The current problem is that the availability of allographs is limited and metal implants are very expensive. Mass production of secretome can make bone reconstruction of massive bone defects using a scaffold more effective and efficient. This study aims to prove bone regeneration in massive bone defects using bovine hydroxyapatite reconstruction with normoxic and hypoxic secretome conditions using collagen type 1 (COL1), alkaline phosphate (ALP), osteonectin (ON), and osteopontin (OPN) parameters. This is an in vivo study using male New Zealand white rabbits aged 6-9 months. The research was carried out at the Biomaterials Center-Tissue Bank, Dr. Soetomo Hospital for the manufacturer of bovine hydroxyapatite (BHA) and secretome BM-MSC culture under normoxic and hypoxic conditions, and UNAIR Tropical Disease Institute for implantation in experimental animals. Data analysis was carried out with the one-way ANOVA statistical test and continued with the Post Hoc test LSD statistical test to determine whether or not there were significant differences between groups. There were significant differences between hypoxic to normoxic group and hypoxic to BHA group at day-30 observation using ALP, COL 1, ON, and OPN parameters. Meanwhile, there is only osteonectin parameter has significant difference at day-30 observation. At day-60 observation, only OPN parameter has significant differences between hypoxic to normoxic and hypoxic to BHA group. Between day-30 and day-60 observation, BHA and normoxic groups have a significant difference at all parameters, but in hypoxic group, there are only difference at ALP, COL 1, and ON parameters. Hypoxic condition BM-MSC secretome with BHA composite is superior and could be an option for treating bone defect.

The hypoxic environment is a substantial factor in maintenance, proliferation, and differentiation of the cell cultures. Low oxygen is known as a potent chondrogenesis stimulus in stem cells that is important for clinical application and engineering of functional cartilage. Hypoxia can potentially induce angiogenesis process by secretion of cytokines. This systematic review goal is to discover the effect of hypoxic condition on tendon/ ligament culture and the best oxygen level of hypoxia for in vitro and in vivo studies. We included 21 articles. A comprehensive review of this database confirms that the hypoxic condition is a substantial factor in the maintenance, proliferation, and differentiation of ligament/tendon cultures. Cell proliferation in the severe hypoxic (oxygen concentration of 1%) group at 24 h postcultivation was considered significant, but cell proliferation was markedly inhibited in the severe hypoxic group after 48 h., (© 2021 The Authors.)

Objectives: Alendronate are widely used in the treatment of bone disorders characterized by inhibit osteoclast-mediated bone resorption such as Paget's disease, fibrous dysplasia, myeloma, bone metastases and osteoporosis. In recent studies alendronate improves proliferation and differentiation of osteoblasts, thereby facilitating for bone regeneration. The disadvantages of this class are their poor bioavailability and side effects on oral and intravenous application such as stomach irritation and osteonecrosis in jaw. Thus, local treatment of alendronate is needed in order to achieve high concentration of drug. Bovine hydroxyapatite-gelatin scaffold with alendronate was studied. Glutaraldehyde was used as cross-linking agent, increase the characteristics of this scaffold. The objectives of this study were to manufacture and characterize alendronate scaffold using bovine hydroxyapatite-gelatin and crosslinked by glutaraldehyde., Methods: Preparation of cross-linked bovine hydroxyapatite-gelatin and alendronate scaffold with different concentration of glutaraldehyde (0.00, 0.50, 0.75, and 1.00%). The scaffolds were characterized for compressive strength, porosity, density, swelling ratio, in vitro degradation, and cytotoxicity (the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, shorted as MTT assay)., Results: Bovine hydroxyapatite-gelatin-alendronate scaffold cross-linked with glutaraldehyde showed lower density than without glutaraldehyde. As glutaraldehyde concentration increased, porosity also increased. Eventually, it reduced compressive strength. Swelling ratio and in vitro degradation was negatively dependent on glutaraldehyde concentration. In addition, the scaffold has a good safety by MTT assay., Conclusions: Bovine hydroxyapatite-gelatin-alendronate scaffold was fabricated with various concentrations of glutaraldehyde. The presence of glutaraldehyde on bovine hydroxyapatite-gelatin-alendronate is safe and suitable candidate scaffold for bone regeneration., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

The use of stem cells is a breakthrough in medical biotechnology which brings regenerative therapy into a new era. Over the past several decades, stem cells had been widely used as regenerative therapy and Mesenchymal Stem Cells (MSCs) had emerged as a promising therapeutic option. Currently stem cells are effective therapeutic agents againts several diseases due to their tissue protective and repair mechanisms. This therapeutic effect is largely due to the biomolecular properties including secretomes. Injury to peripheral nerves has significant health and economic consequences, and no surgical procedure can completely restore sensory and motor function. Stem cell therapy in peripheral nerve injury is an important future intervention to achieve the best clinical outcome improvement. Adipose mesenchymal stem cells (AdMSCs) are multipotent mesenchymal stem cells which are similar to bone marrow-derived mesenchymal stem cells (BM-MSCs). The following review aims to provide an overview of the use of AdMSCs and their secretomes in regenerating peripheral nerves., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2021 The Authors.)

The advanced, metastasis, and reccurent of osteosarcoma (OS) patients have a poor prognosis postaggresive surgery and chemotherapy. Peripheral blood mononuclear cells (PBMCs) as cell-based immunotherapy may successful in the OS treatment. To investigate the enhancement apoptosis of OS-mesenchymal stem cells (OS-MSCs) co-cultivated with PBMCs sensitized using the secretome and granulocyte macrophage colony-stimulating factor (GMCSF). This true experimental study with posttest only control group design and in vitro study. The sample was cultured OS-MSCs which confirmed by Cluster of Differentiation-133 using immunocytochemistry (ICC) and histopathology analysis. The sample divided into six groups accordingly: OS-MSC, OS-MSC + PMBC, OS-MSC + PMBC + Secretome, OS-MSC + PMBC + GMCSF, OS-MSC + PBMC + Secretome + GMCSF ( n = 5/N = 30). The enhancement of OS-MSCs apoptosis was analyzed through Interleukin-2 (IL-2) level through the Enyzme-Linked Immunosorbent Assay examination, expression of Signal Transducers and Activators of Transcription (STAT)-3 and caspase-3 by ICC. One-way analysis of variance test and Tukey Honestly Significant Difference to analyze the difference between the groups ( P < 0.05). The highest of IL-2 level was found in the PBMC + Secretome + GMCSF group. The highest expression of caspase-3 was found in OS-MSC + PBMC + Secretome + GMCSF group with significant different between groups ( P < 0.05). There was insignificant difference of STAT-3 epxression and IL-2 level between groups ( P > 0.05). The co-cultivation of OS-MSCs and PBMSCs activated using secretome and GMCSF has a great ability to enhance OS-MSCs apoptosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Advanced Pharmaceutical Technology & Research.)

Purpose: This study aimed to determine the number of posterior cruciate ligament (PCL) publications performed in Asian countries and to identify factors associated with research output in this region., Materials and Methods: Searches of existing academic journal articles were performed using PubMed, Google Scholar, and the Cochrane Library from January 1, 2009 until December 31, 2019., Results: A total of 265 articles were published in the last 10 years in Asian countries, with an increase in publications after 2010 and an average of 26 articles every year. More than half (70%) of the articles were published in journals with an impact factor (IF) ≥1. The majority of the publications were cohort studies (27%), followed by case reports (16%), systematic reviews/meta-analyses (2.6%), laboratory studies (1.8%), and case-control studies (1.5%). South Korea and China had the most PCL publications, and most authors were from South Korea., Conclusion: The PCL research output in Asia is low in quantity but high in quality publications, and the majority of publications come from South Korea, China and Japan, with most being cohort studies and case reports., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© 2020 The Author(s).)

Background: Soft tissue sarcoma is one cause of mortality in adult malignancies. This tumor is rare, persistent, and highly-recurrent. Many patients are came in late stage. It is important to identify a prognostic tool that is reliable, easily obtainable, and widely applicable. The aim of this study is to investigate and analyze the prognostic value of clinicopathological and biomarker factors in patients with soft tissue sarcoma., Methods: This retrospective study extracts data from the musculoskeletal tumor registry from January 2012 to December 2018 in a single tertiary hospital. Eighty patients with diagnosis of soft tissue sarcoma were included. Preoperative modified Glasgow Prognostic Score, Neutrophils/Lymphocytes Ratio, Hemoglobin, serum lactate dehydrogenase data were analyzed along with demographic, clinical, radiological and histopathological data. The relationship between variables on overall survival, distant metastasis, and local recurrence were evaluated using univariate and multivariate Cox regression., Results: On univariate analysis, there was significant relationship between hemoglobin, Neutrophils/Lymphocytes Ratio and modified Glasgow Prognostic Score with overall survival (p = 0.031, HR = 1.99; p = 0.04, HR = 1.129; and p = 0.044, HR = 3.89). A significant relationship was found between age and soft tissue sarcoma stage with distant metastasis (p = 0.046, HR = 1.95; and p = 0.00, HR = 3.22). In addition, we also found significant relationship between surgical margin with local recurrence (p = 0.018, OR = 3.44). However, on multivariate analysis the independent prognostic factor for overall survival was only modified Glasgow Prognostic Score (HR = 2.138; p = 0.011). Stage IIIA (HR = 5.32; p = 0.005) and IIIB (HR = 13.48; p = 0.00) were independent prognostic for distant metastasis. Surgical margin was independently associated with local recurrence (HR = 14.84; p = 0.001)., Conclusion: Modified Glasgow Prognostic Score can be used as prognostic tool of overall survival in soft tissue sarcoma patients. Moreover, stage of STS and surgical margin can be used as a prognostic factor for distant metastasis and local recurrence of soft tissue sarcoma respectively., Competing Interests: The authors declare no conflict of interest in this study., (© 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd.)

Background: Tendon or ligament tears can decrease patients' quality of life. Many therapeutic interventions are available to treat such injuries. Mesenchymal stem cells (MSCs) have been shown to be effective in treating tendon or ligament tears; however, the use of stem cell-conditioned medium (CM) requires further investigation. This review focused on the use of stem cell CM as treatment for tendon or ligament tears., Methods: A systematic literature search was performed on PubMed (MEDLINE), OVID, EMBASE, the Cochrane Library, Scopus, Web of Science, and Science Direct with the terms conditioned media or conditioned medium or secretome or microvesicle or extracellular vesicle or exosome, and tendon or ligament as the search keywords. A total of 852 articles were reviewed. Five articles were identified as relevant for this systematic review., Results: Meta-analysis could not be performed because of the high heterogeneity of the reviewed studies; however, the results of this study support a positive effect of conditioned media in tendon and ligament treatment., Conclusion: This review provides evidence of improvement in the tendon and ligament healing process with stem cell CM therapy in preclinical studies., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Background: The posterior cruciate ligament (PCL) is one of the rare operated ligament of the knee. Details on the top journals, universities, and authors on the topic would be helpful to identify the sources of information for clinical and research queries as well as to observe trends for future research and identify universities/authors of particular interest for training or to follow their research., Purpose: To consolidate information from PubMed on the PCL from 2009 to 2019, spanning 10 years., Study Design: Cross-sectional study., Methods: A search of the PubMed database was conducted for the PCL, and 593 articles published over the past 10 years were analysed for further details. These details included the number of publications per year, top 10 journals publishing on the PCL, top 10 first authors publishing articles on the PCL., Results: The top journal and top author in all position publishing on the PCL were Knee surgery, sports traumatology, arthroscopy and Robert F. LaPrade, respectively. The most articles published by a first author were by Yong Seuk Lee. The United States was the most published country, and 4 of the top 10 affiliations were from this country., Conclusion: Mining the data on the PCL in PubMed produced useful information about good sources of publications on this topic, including authors/journals that could be followed. The strength of their association with other authors could potentially indicate co-workers, common research interests, and collaborative studies., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2020 The Authors.)

Tissue engineering had been believed to overcome the limitation of cartilage lesions treatment. Nowadays the studies focus on using mesenchymal stem cells in scaffold. A biodegradable porous sponge bovine cartilage scaffold is expected to have the physicobiochemical characterization to promote chondrogenic differentiation of hBM-MSCs. Scaffold from bovine cartilage was printed in 5 mm diameter sponge, categorized into nondecellularized (SBCS) and decellularized (DSBCS). Physical characteristics (pore diameter and interconnectivity) were done using a Scanning Electron Microscope (SEM). Biodegradability assessment used Phosphate Buffered Saline in 15, 30, 60 minutes, 6, 24, 48, 72 hours, and 1, 2 weeks. The swelling ratios were counted in 5, 10, 15, 30, 60, and 360 minutes. Biochemical characteristics were obtained by enzyme-linked immunosorbent assay for type II collagen, aggrecan, and Transforming Growth Factors- β (TGF- β ). Data were statistically compared. hBM-MSCs were seeded on both scaffolds. Histological examination used hematoxylin-eosin taken at the 2nd and 4th weeks after seeding. There was no significant difference (p=0.473; p=0.142) on mean porosity 90.07 ± 4.64% vs. 88.93 ± 4.18% and pore diameter 111.83 ± 14.23  μ m vs. 105.29 ± 11.14  μ m assessment between SBCS and DSBCS groups. Scaffolds from both groups showed pore interconnectivity. DSBCS group had faster biodegradability. SBCS group sweals better. SBCS group contains type II collagen, aggrecan, and TGF- β with mean values 380.78 ± 18.63 ng/ml, 30.71 ± 4.50 ng/ml, and 130.12 ± 7.73 ng/ml, respectively, while DSBCS contained type II collagen, aggrecan, and TGF- β with mean values 64.83 ± 13.54 ng/ml, 8.41 ± 2.38 ng/ml, and 16.39 ± 4.49 ng/ml, respectively. The results were statistically different (p<0.001). Chondrocytes were found within scaffold on the 2nd and 4th weeks. Physicobiochemical characteristic of biodegradable sponge bovine cartilage scaffold promotes chondrogenic differentiation of hBM-MSCs.

Introduction: Nonunion due to a critical-sized bone defect is a complicated problem. The healing process must fulfill three mandatory elements of osteogenesis, osteoinduction, and osteoconduction. One ideal source to provide an abundant number of osteogenic cells is from the process of the culture of bone marrow stem cells which demands the availability of processing facility. Unfortunately, this sophisticated option is not always feasible in every hospital in low-income to middle-income countries. We tried to fulfill the requirement of osteogenic cells by using simple and cost-effective bone marrow aspirate. We presented two cases of critical-sized diaphyseal bone defect treated with the combination of bone marrow aspirate, cancellous bone allograft, and platelet-rich plasma (PRP). Presentation of cases: The defect sizes were five and six centimeters in humerus and tibia respectively. We applied a combination of bone marrow aspirate, cancellous bone allograft, and PRP to promote bone healing in the defect sites. Both patients have achieved the good clinical and radiological outcome., Discussion: Critical-sized bone defects require the application of tissue engineering. Aspirated bone marrow can be used as a more affordable option to provide the element of osteogenic cells in bone healing. Combined with cancellous bone allograft and PRP, they fulfill the required ingredients to promote bone regeneration., Conclusion: Bone defects remain one of the most challenging conditions to treat in orthopedic. There are many options to treat the defect but the fundamental prerequisites of cells, scaffolds and growth factors for healing have developed into the concept of tissue engineering: osteogenesis, osteoinduction, and osteoconduction., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Knee osteoarthritis has a high prevalence in Indonesia. Aim of this research is knowing the outcome of knee osteoarthritis patient after PFO procedure., Methods: Data collected and analyzed in hospitals in Surabaya from July to December 2017. This study compares preoperative and postoperative outcome on radiological evaluation, patient satisfaction, and clinical function., Results: The study includes 15 patients. Radiological evaluation on Tibiofemoral Angle and Joint Space Ratio increases significantly. Patient satisfaction evaluation using SF12 significantly improve. Evaluation using KOOS and Oxford Knee Score also increase significantly., Conclusion: PFO could become an alternative treatment for last stage knee osteoarthritis.

Introduction: Knee osteoarthritis with valgus deformity presents a surgical challenge that must be solved during total knee arthroplasty (TKA). In some case whereby ligament imbalance is found, constrained implant should be used. Unfortunately, the implant is not always readily accessible in some developing countries. The objective of this paper is to provide alternative solution to such case., Presentation of Case: We reported a 71-year-old female patient with a painful and fixed valgus deformity of her right knee. Preoperatively, the patient's right knee range of motion (ROM) was 10-145° of flexion with a 32° fixed valgus deformity. A constrained implant was not accessible. To balance the ligament, Medial Collateral Ligament (MCL) origin was shifted to superior and anterior. A non-constrained implant was used. The valgus deformity was corrected intraoperatively and ROM achieved 0-140° of flexion., Discussion: It is crucial that attention is given not only to the restoration of proper bony alignment but even more importantly to soft tissue balancing. By using the non-constrained implant, the cost can also be reduced and suitable for developing countries with limited coverage of state insurance., Conclusion: Three months after the surgery, the patient achieved stable and painless knee with 10-90° of flexion and complete correction of her valgus deformity., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Object: Stroke, one of the most devastating diseases, is a leading cause of death and disability throughout the world and is also associated with emotional and economic problems. The main goal of this study was to investigate the clinical outcome of the intraventricular transplantation of bone marrow mesenchymal stem cells (BM-MSCs) in post-haemorrhagic stroke patients., Method: This study was done consisting of eight patients with supratentorial haemorrhagic stroke, who had undergone 24 weeks of standard treatment of stroke with stable neurological deficits. All of the patients received stem cell transplantation intraventricularly using autologous BM-MSCs. Six months and Twelve months after stem cells treatment, the clinical outcomes were measured using the National Institute of Health Stroke Scale (NIHSS) and adverse effect also observed., Result: The results of this study showed improvement of NIHSS score values before and after the treatment in five patients. No adverse effects or complications were detected during the 1-year observation., Conclusion: Intraventricular transplantation of BM-MSCs has shown benefits in improving the functional status of post-haemorrhagic stroke patients with no adverse effect.

Autogenous bone graft is gold standard in treating bone defects, but it might have difficulty in corporation and rejection reaction. This study is to compare the effectiveness among freeze-dried xenograft, freeze-dried allograft, hydroxyapatite xenograft, and demineralized bone matrix xenograft as bone graft to fill bone defect in femoral diaphysis of white rabbit. Thirty male New Zealand white rabbits were distributed into five groups. Bone defect was filled correspondingly with xenograft freeze-dried cortical bovine, allograft freeze-dried cortical New Zealand white rabbit, xenograft hydroxyapatite bovine, and xenograft demineralized bone matrix bovine. No graft was used in control group. VEGF, osteoblast, and woven bone were higher in allograft freeze-dried cortical New Zealand white rabbit (mean 5.6625 ( p < 0.05)) and xenograft demineralized bone matrix bovine (mean 5.2475 ( p < 0.05)) with calcification of woven bone was already seen in week 2 in the latter group. There was a decrease of woven bone (mean 4.685 ( p < 0.05)) fibrous tissue (mean 41.07 ( p < 0.05)) in xenograft demineralized bone matrix bovine. The Immunoglobulin-G was elevated in control and all study groups but not significantly ( p = 0.07855). Bone healing process in xenograft demineralized bone matrix bovine is more effective than in xenograft hydroxyapatite bovine, allograft freeze-dried New Zealand white rabbit, xenograft freeze-dried cortical bovine, and control.