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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

Purpose: This study aimed to compare the return to sports, return to competition, Tegner score and anterior cruciate ligament-return to sports injury (ACL-RSI) scores between patients who underwent ACL reconstruction (ACLR) combined with anterolateral ligament reconstruction (ALLR) and those who underwent ACLR alone., Methods: Two independent reviewers conducted a literature search in PubMed (MEDLINE), EMBASE, Google Scholar and the Cochrane Library in July 2024, followed by data extraction and quality assessment. This study followed the Preferred Reporting Items for Systematic Reviews and meta-analysis guidelines. The return to sports rate, return to competition rate, Tegner score and ACL-RSI score were compared between patients who underwent primary ACLR with ALLR and those who underwent isolated primary or revision ACLR. The methodological quality of the included studies was assessed via the Cochrane risk-of-bias tool and methodological items for nonrandomized studies., Results: In total, 12,139 studies were screened, and 14 (four randomized controlled trials and 10 nonrandomized studies) studies were ultimately evaluated. Compared with isolated ACLR, ACLR combined with ALLR resulted in a higher rate of return to sports and competition. Nevertheless, no significant differences were found in the Tegner score or ACL-RSI score between the two groups., Conclusion: Patients who underwent ACLR in combination with ALLR had higher rates of return to sports and competition, but their Tegner activity and ACL-RSI scores were similar to those of patients who underwent ACLR alone. This finding may assist surgeons in making decisions when treating patients undergoing ACLR, especially athletes., Level of Evidence: Level III., Competing Interests: One of the authors, N. C. B., receives payment or benefits from DePuy Johnson & Johnson and Zimmer Biomet and sits on the editorial board of BJJ, CORR, OJSM, Journal of Orthopaedic Surgery. The remaining authors declare no conflicts of interest., (© 2025 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

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 Banff Patellar Instability Instrument (BPII) is a valuable scoring tool for assessing patellofemoral instability in patients suffering from patellofemoral pain syndrome (PFPS). The BPII 2.0 is a shortened version of the BPII. However, there is no Indonesian edition of BPII 2.0 that has been validated. This study aimed to determine the validity and reliability of the Indonesian version of the BPII 2.0., Materials and Methods: This was a cross-sectional study that used a forward-backward translation protocol to create an Indonesian version of the BPII 2.0. Thirty patients with PFPS were given the questionnaires. The questionnaire's validity was evaluated by analyzing the correlation between score of each subscale and the overall score to the Indonesian version of the Kujala score using Pearson correlation coefficient, while the reliability was evaluated by measuring the internal consistency (Cronbach α) and test-retest reliability (intraclass correlation coefficient)., Results: The Indonesian version of BPII 2.0 and the Indonesian version of Kujala score had a strong Pearson correlation coefficient for construct validity. For all subscales, Cronbach α was 0.90-0.98, indicating adequate internal consistency. The test-retest reliability was high, with intraclass correlation coefficient ranging from 0.89 to 0.98 for all subscales. There was no difference in the Indonesian version of BPII 2.0 response between the first and second administration of the questionnaire which was taken 7 days afterward., Conclusion: The Indonesian version of BPII 2.0 was determined to be valid and reliable and is therefore an objective instrument to evaluate patellofemoral instability in patients with PFPS in the Indonesian population., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Study Design: Experimental animal study., Purpose: This study aims to investigate the effects of treatment with human neural stem cell (HNSC) secretomes on subacute spinal cord injury (SCI) post-laminectomy by analyzing interleukin-10 (IL-10), matrix metalloproteinase 9 (MMP9), transforming growth factor-β (TGF-β), and Basso-Beattie-Bresnahan (BBB) score locomotors as expressions of neurological recovery., Overview of Literature: In the United States, SCI has a recovery rate of 0.08%, tetraplegia 58.7%, and paraplegia 40.6%. Therapeutic approaches to SCI have focused on modulating the secondary cascade to prevent neurological deterioration and glial scar formation. Increasing evidence has shown that the success of cell-based SCI therapy is attributed to the secretomes rather than the cells themselves, but the effect of treatment with HNSC secretomes in SCI is unclear., Methods: This experimental study investigated 15 Rattus norvegicus rats that were divided into three groups: (1) normal, (2) SCI+nonsecretome, and (3) SCI+secretome (30 μL, intrathecal Th10). Model subacute SCI post-laminectomy was performed in 60 seconds using an aneurysm Yasargil clip with a closing forceps weighing 65 g (150 kdyn). At 35 days post-injury, the specimens were collected, and the immunohistochemicals of IL-10, MMP9, and TGF-β were analyzed. Motor recovery was evaluated based on the BBB scores., Results: The SCI post-laminectomy of rats treated with HNSC secretomes showed improvements in their locomotor recovery based on the BBB scores (p =0.000, mean=18.4) and decreased MMP9 (p =0.015) but had increased the levels of IL-10 (p =0.045) and TGF-β (p =0.01)., Conclusions: These results indicate that the factors associated with the HNSC secretomes can mitigate their pathophysiological processes of secondary damage after SCI and improve the locomotor functional outcomes in rats.

Background: Globally, complete neurological recovery of spinal cord injury (SCI) is still less than 1%, and 90% experience permanent disability. The key issue is that a pharmacological neuroprotective-neuroregenerative agent and SCI regeneration mechanism have not been found. The secretomes of stem cell are an emerging neurotrophic agent, but the effect of human neural stem cells (HNSCs) secretome on SCI is still unclear., Aim: To investigate the regeneration mechanism of SCI and neuroprotective-neuroregenerative effects of HNSCs-secretome on subacute SCI post-laminectomy in rats., Methods: An experimental study was conducted with 45 Rattus norvegicus, divided into 15 normal, 15 control (10 mL physiologic saline), and 15 treatment (30 μL HNSCs-secretome, intrathecal T10, three days post-traumatic). Locomotor function was evaluated weekly by blinded evaluators. Fifty-six days post-injury, specimens were collected, and spinal cord lesion, free radical oxidative stress (F2-Isoprostanes), nuclear factor-kappa B (NF-κB), matrix metallopeptidase 9 (MMP9), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), B cell lymphoma-2 (Bcl-2), nestin, brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) were analyzed. The SCI regeneration mechanism was analyzed using partial least squares structural equation modeling (PLS SEM)., Results: HNSCs-secretome significantly improved locomotor recovery according to Basso, Beattie, Bresnahan (BBB) scores and increased neurogenesis (nestin, BDNF, and GDNF), neuroangiogenesis (VEGF), anti-apoptotic (Bcl-2), anti-inflammatory (IL-10 and TGF-β), but decreased pro-inflammatory (NF-κB, MMP9, TNF-α), F2-Isoprostanes, and spinal cord lesion size. The SCI regeneration mechanism is valid by analyzed outer model, inner model, and hypothesis testing in PLS SEM, started with pro-inflammation followed by anti-inflammation, anti-apoptotic, neuroangiogenesis, neurogenesis, and locomotor function., Conclusion: HNSCs-secretome as a potential neuroprotective-neuroregenerative agent for the treatment of SCI and uncover the SCI regeneration mechanism., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This study aims to prove the healing results (regeneration) in cartilage defects using a combination treatment of microfractures and transplantation synovium-platelet rich fibrin (S-PRF)., Methods: A cartilage defect was made in the trochlear groove of the knee of adult New Zealand white rabbits, and was classified into three treatment groups. The group 1 was cartilage defect without treatment, 2 with microfracture treatment, and 3 with microfracture covered with a synovium-platelet rich fibrin (S-PRF) membrane. Twelve weeks after the intervention, the animals were macroscopically and histologically examined, and evaluated by the International Cartilage Repair Society (ICRS). Additionally, the expression of aggrecan and type 2 collagen was examined by real-time-PCR., Results: The ICSR scores for macroscopic were significantly higher in the microfracture and S-PRF transplant group than in the other groups. Also, the ICSR scores for histology were significantly higher in this group. The expression of aggrecan and type 2 collagen was higher in the group that received complete treatment., Conclusions: Microfractures and transplantation of synovium-platelet rich fibrin (S-PRF) can regenerate knee cartilage defects which have been shown to increase the expression of mRNA aggrecan and mRNA type 2 collagen resulting in excellent repair., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities., Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 μL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale., Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation., Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Background : Periprosthetic joint infection is the most common infection due to joint replacement. It has been reported that, over a 5-year time span, 3.7 % of cases occurred annually. This statistic has increased to 6.86 % over 16 years. Thus, an effective method is required to reduce these complications. Several strategies such as coating methods with various materials, such as antibiotics, silver, and iodine, have been reported. However, the best preventive strategy is still undetermined. Therefore, this systematic review aims to evaluate the outcome of coating methods on joint arthroplasty as a treatment or preventive management for infection complications. Methods : Eligible articles were systematically searched from multiple electronic databases (PubMed, Cochrane library, and ScienceDirect) up to 2 June 2022. Based on the criterion inclusion, eight articles were selected for this study. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the study, and the meta-analysis test was conducted with Review Manager 5.4. Results : The quality of the articles in this study is in the range of moderate to good. It was found that the application of modified antibiotic coatings significantly reduced the occurrence of periprosthetic joint infection (PJI) ( p 0.03), and silver coating could not significantly ( p 0.47) prevent the occurrence of PJI. However, according to the whole aspect of coating modification, the use of antibiotics, silver, and iodine can minimize the occurrence of PJI ( p   < 0.0001 ). Conclusion : Coating methods using antibiotics are an effective method that could significantly prevent the occurrence of PJI. On the other hand, coating with non-antibiotic materials such as silver could not significantly prevent the incidence of PJI., Competing Interests: The contact author has declared that none of the authors has any competing interests., (Copyright: © 2022 Krisna Yuarno Phatama et al.)

Background: Elderly with the locomotive syndrome is at high risk for fall and fractures. Thus multimodal therapy is needed to minimize the risk., Objective: Analyzing the effect of combined locomotor training and aerobic exercise on muscle strength in elderly with locomotive syndrome stage 1., Methods: This study used a pre-test and post-test design with 20 participants (treatment group = 10 participants and control group = 10 participants). The treatment group was given combined locomotor training and aerobic exercise, while the control group was only given aerobic exercise for eight weeks. Locomotor training was provided three times/week with progressive increase of set and repetition at each activity. Meanwhile, aerobic exercise was given seven times/week for 30 min per session. Participants were examined for muscle strength (handgrip strength) before and after the intervention. The analysis included paired t -test and an independent t -test with a p -value <0.05., Results: The participants' mean age was 73.85 ± 4.75 years, with treatment group = 75.4 ± 4.88 years and control group = 72.3 ± 4.30 years ( t  = 1.508; 95% CI = -1.220 - 7420; p  = 0.149). The HGS values in the treatment group were 13.89 ± 5.27 (pre-test) and 19.06 ± 4.54 (post-test; t  = 11.765; 95% CI = -6.164 to -4.176; p  < 0.001). Meanwhile, the HGS values in the control group at pre-test and post-test were 11.27 ± 2.17 and 13.03 ± 2.54, respectively ( t  = 2.057; 95% CI = -1.600 - 0.076; p  = 0.070). The ΔHGS values of treatment and control group were 5.17 ± 1.39 and 1.76 ± 2.07, respectively ( t  = 4.329; 95% CI = 1.755-5.065; p  < 0.001)., Conclusion: Combined locomotor training and aerobic exercise have increased muscle strength, as proven by increased handgrip strength., Competing Interests: Ajeng Hayu Nayasista, Damayanti Tinduh, I Putu Alit Pawana, Sri Mardjiati Mei Wulan, Dwikora Novembri Utomo, and Melaniani Soenarnatalina declare that they have no conflict of interest., (© 2022 The Authors.)

Background: The purpose of this study was to analyze the response of inflammatory cytokines interleukin-8 (IL-8) and NF-κB to the closure of skull defect with periosteum as a scaffolding material in bone healing used after surgery., Methods: Thirty Oryctolagus cuniculus rabbits underwent a craniotomy to create a 20 mm diameter round defect in the parietal bones. The parietal bones were returned to its place and stabilized by an internal plate fixation. The defects were either left empty or implanted with periosteum. At 6 weeks, the specimens were euthanized and examined., Results: Histological examination showed a more well-developed formation of woven bone in the periosteum group. Immunohistochemical examinations showed that the use of periosteum in the closure of skull defects reduced the NF-κB and IL-8 response which affected the ossification process., Conclusion: The experiment showed that the use of periosteum was linked with IL-8 and NF-κB downregulation toward ossification effects at any point throughout the trial. Periosteum usage might be beneficial as a scaffolding material in bone healing for autograft cranioplasty in animal model and could be applied to clinical practice., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

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.)

Background: COVID-19 can infect an asymptomatic person silently without any overt symptoms despite diffuse blood clots throughout the body. Clot formation is induced by COVID-19 associated coagulopathy that can cause a high mortality rate. D-dimer, a fairly decisive marker for the coagulopathy event, is physiologically a marker of the fibrinolysis process. The increase of D-dimers in COVID-19 cases must be followed up because it relates to the initiation of a cytokine storm. Case presentation: We report an asymptomatic patient with sudden D-dimer elevation who received anticoagulant therapy. After three days of heparin administration, D-dimer results became normal and anticoagulant therapy was stopped. However, on the 12th day, the D-dimer level rebounded back and was followed by an increase of hs-C-reactive protein, erythrocyte sedimentation rate, IL-6, although SARS-CoV-2 PCR result became negative. A hyperglycaemic reaction and a sudden increase of HbA1C was observed in the patient. After three weeks D-dimer had returned to normal levels, and so did the other markers. The patient recovered fully and still no symptoms were obvious. Conclusion: COVID-19 patients without symptoms may be at risk of an asymptomatic coagulopathy process. The decreasing level of D-dimer erroneously cannot ensure that the coagulopathy process stops., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Caesario J et al.)

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.)

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.)

Purpose: The aim of this study was to evaluate the anthropometric differences between knees of Indonesian Asians and Dutch Caucasians and the fit of nine different knee implant systems., Methods: A total of 268 anteroposterior (AP) and lateral knee preoperative radiographs from 134 consecutive patients scheduled for total knee arthroplasty at two different centres in Jakarta and Leiden were included. Both patient groups were matched according to age and sex and included 67 Asians and 67 Caucasians. We assessed the radiographic differences between the Asian and Caucasian anthropometric data. The dimensions of the nine knee implant designs (Vanguard, Genesis II, Persona Standard, Persona Narrow, GK Sphere, Gemini, Attune Standard, Attune Narrow, and Sigma PFC) were compared with the patients' anthropometric (distal femur and proximal tibia) measurements., Results: The Dutch Caucasian patients had larger mediolateral (ML) and AP femoral and tibial dimensions than the Indonesian Asians. The aspect ratios of the distal femur and tibia were larger in Asians than in Caucasians. The AP and ML dimensions were mismatched between the tibial components of the nine knee systems and the Asian anthropometric data. Both groups had larger ML distal femoral dimensions than the knee systems., Conclusion: Absolute and relative differences in knee dimensions exist not only between Asian and Caucasian knees but also within both groups. Not all TKA systems had a good fit with the Asian and Caucasian knee phenotypes. An increase in the range of available knee component sizes would be beneficial, although TKA remains an adequate compromise., Level of Evidence: III.

Background: The anterolateral ligament (ALL) of the knee remains a topic of interest. All aspects of the ligament, including its anatomy, biomechanics, imaging, and clinical importance, are areas for research among knee surgeons., Purpose: To evaluate the trends in research on the ALL of the knee, as indicated by studies indexed in PubMed from 2010 to 2019., Study Design: Cross-sectional study., Methods: We searched PubMed for article titles from January 1, 2010, to December 31, 2019, that included the term "anterolateral ligament." The initial search was performed with the terms "anterolateral ligament AND knee" and "anterolateral ligament NOT knee." Next, we performed a search using "anterolateral complex OR anterolateral reconstruction OR lateral extra-articular tenodesis" to avoid missing any studies. A bibliometric evaluation was performed for the search results, and we noted the characteristics of the most cited articles in PubMed., Results: Published studies on the ALL peaked in 2017, with 56 studies, and then declined from 2017 to 2019. The 3 leading journals with articles on the ALL were Arthroscopy ; Knee Surgery, Sports Traumatology, Arthroscopy ; and The American Journal of Sports Medicine . Cadaveric anatomic, cadaveric biomechanical, and clinical imaging studies of the ALL were the most common types of studies published from 2010 to 2019. Clinical studies on the ALL consisted of 18 articles, with the majority displaying a low level of evidence., Conclusion: Cadaveric anatomic/histological, cadaveric biomechanical, and clinical imaging studies of the ALL were the most commonly published studies from 2010 to 2019. More clinical outcome studies with a high level of evidence are needed to increase the supporting data for the future practice of ALL reconstruction., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

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).)

Introduction: Articular cartilage is an avascular, alymphatic, and anisotropic tissue, these characteristics cause significant healing problems to injuries to the cartilage tissue. To overcome this problem, various techniques have been developed and widely used, but the cost-effectiveness and resulting tissue regeneration have never achieved hyaline-like cartilage that has the best biomechanical properties. The idea of this experiment is to use a Biodegradable Porous Sponge Cartilage (BPSC) Scaffold to enhance the regeneration of hyaline-like cartilage combined with microfracture technique and Adipose Derived Stem Cells (ASCs) or secretome on an animal model., Methods: A model defect was made on the femoral trochlea of a New Zealand white rabbit. Four groups were made to compare different treatment methods for osteochondral defects. The groups were: (1) Control group; (2) Scaffold Group; (3) Scaffold + ASCs Group; (4) Scaffold + Secretome Group. After 12 weeks, we terminate the animal models, then a macroscopic evaluation using the International Cartilage Research Society (ICRS) scoring system and Oswestry Arthroscopy Score (OAS) was done, followed by sectioning the specimen for microscopic evaluation using the O ' Driscoll scoring system., Results: The mean score for all treatment group were better compared to the control group grossly and histologically. The best mean score for macroscopic and microscopic evaluation was the group given Scaffold + ASCs., Conclusion: The application of BPSC scaffold enhances cartilage regeneration in larger osteochondral defects. Furthermore, the addition of ASCs or secretome along with the scaffold implantation further enhances the cartilage regeneration, in which ASCs shows better results.

Background: Anterior knee pain, which has a prevalence of 4% to 49% after TKA, may be a cause of patient dissatisfaction after TKA. To limit the occurrence of anterior knee pain, patellar denervation with electrocautery has been proposed. However, studies have disagreed as to the efficacy of this procedure.Questions/purposes We evaluated patients undergoing bilateral, simultaneous TKA procedures without patellar resurfacing to ask: (1) Does circumferential patellar cauterization decrease anterior knee pain (Kujala score) postoperatively compared with non-cauterization of the patella? (2) Does circumferential patellar cauterization result in better functional outcomes based on patient report (VAS score, Oxford knee score, and Knee Injury and Osteoarthritis Outcome Score) than non-cauterization of the patella? (3) Is there any difference in the complication rate (infection, patellar maltracking, fracture, venous thromboembolism, or reoperation rate) between cauterized patellae and non-cauterized patellae?, Methods: Seventy-eight patients (156 knees) were included in this prospective, quasi-randomized study, with each patient serving as his or her own control. Patellar cauterization was always performed on the right knee during simultaneous, bilateral TKA. Five patients (6%) were lost to follow-up before the 2-year minimum follow-up interval. A single surgeon performed all TKAs using the same type of implant, and osteophyte excision was performed in all patellae, which were left unresurfaced. Patellar cauterization was performed at 2 mm to 3 mm deep and approximately 5 mm circumferentially away from the patellar rim. The preoperative femorotibial angle and degree of osteoarthritis (according to the Kellgren-Lawrence grading system) were measured. Restoration of the patellofemoral joint was assessed using the anterior condylar ratio. Clinical outcomes, consisting of clinician-reported outcomes (ROM and Kujala score) and patient-reported outcomes (VAS pain score, Oxford knee score, and Knee Injury and Osteoarthritis Outcome Score), were evaluated preoperatively and at 1 month and 2 years postoperatively. Preoperatively, the radiologic severity of osteoarthritis, based on the Kellgren-Lawrence classification, was not different between the two groups, nor were the baseline pain and knee scores. The mean femorotibial angle of the two groups was also comparable: 189° ± 4.9° and 191° ± 6.3° preoperatively (p = 0.051) and 177° ± 2.9° and 178° ± 2.1° postoperatively (p = 0.751) for cauterized and non-cauterized knees, respectively. The preoperative (0.3 ± 0.06 versus 0.3 ± 0.07; p = 0.744) and postoperative (0.3 ± 0.06 versus 0.2 ± 0.07; p = 0.192) anterior condylar ratios were also not different between the cauterized and non-cauterized groups., Results: At the 2-year follow-up interval, no difference was observed in the mean Kujala score (82 ± 2.9 and 83 ± 2.6 for cauterized and non-cauterized knees, respectively; mean difference 0.3; 95% confidence interval, -0.599 to 1.202; p = 0.509). The mean VAS pain score was 3 ± 0.9 in the cauterized knee and 3 ± 0.7 in the non-cauterized knee (p = 0.920). The mean ROM was 123° ± 10.8° in the cauterized knee and 123° ± 10.2° in the non-cauterized knee (p = 0.783). There was no difference between cauterized and non-cauterized patellae in the mean Knee Injury and Osteoarthritis Outcome Score for symptoms (86 ± 4.5 versus 86 ± 3.9; p = 0.884), pain (86 ± 3.8 versus 86 ± 3.6; p = 0.905), activities (83 ± 3.2 versus 83 ± 2.8; p = 0.967), sports (42 ± 11.3 versus 43 ± 11.4; p = 0.942), and quality of life (83 ± 4.9 versus 83 ± 4.7; p = 0.916), as well as in the Oxford knee score (40 ± 2.1 versus 41 ± 1.9; p = 0.771). Complications were uncommon and there were no differences between the groups (one deep venous thromboembolism in the cauterized group and two in the control group; odds ratio 0.49, 95% CI, 0.04-5.56; p = 0.57)., Conclusions: Patellar cauterization results in no difference in anterior knee pain, functional outcomes, and complication rates compared with non-cauterization of the patella in patients who undergo non-resurfaced, simultaneous, bilateral, primary TKA with a minimum of 2 years of follow-up. We do not recommend circumferential patellar cauterization in non-resurfaced patellae in patients who undergo TKA., Level of Evidence: Level II, therapeutic study.

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.)

Background: Total Hip Arthroplasty (THA) is one of many therapies given to hip joint injury patients. The main indication for THA in elderly patients is degenerative diseases of the joints. One of the difficulties encountered in this THA procedure is to overcome the acetabulum deficiency, with Paprosky Classification. This study aims to evaluate patients with acetabulum defect that have undergone THA at Dr. Soetomo Hospital in 2014-2016., Methods: This was an observational retrospective study with descriptive analysis. The sample amount was 20 patients, from 80 patients who had THA procedure. Patients were evaluated based on the wear from acetabulum, migration from a cup, the presence of bone loss, heterotopic ossification, and also clinical condition based on Harris Hip Score. The presented results were analyzed by using Kruskal-Wallis on SPSS 19.0 for Windows Program., Results: Hypothesis testing was performed on THA patients based on acetabulum defect type I, II, and III in one, two, and three years after surgery respectively. Massin Score resulted no differences with p = 0.156, p = 0.574, and p = 0223. Bone Loss Classification resulted no differences with p = 0.296, p = 0.287, and p = 0223. No difference on Wear Rate with p = 0.072, p = 0.110, and p = 0.325. There was no difference of Harris Hip Score with p = 0.320, p = 0.082, and p = 0.472., Conclusion: There were no significant differences in radiological evaluation of the Migration Rate, Heterotopic Ossification or Bone Loss, Wear Rate, and on clinical evaluation of Harris Hip Score in all three groups of evaluated acetabulum defects.

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: The high rate of recurrence in patellar dislocation treatment, requires a more comprehensive action, this is due to causes not only single but often multifactorial, including problems with static stability, dynamic stability or both., Presentation of Case: 1 st case: A-39-years-old male, complain of irreducible right patella dislocation with valgus knee and already done soft tissue procedure for patella dislocation. Long-leg radiographs of the right leg showed 18° valgus mechanical angle. 2 nd case: A-26-years-old obese female, complain of dislocation of left patella and history of surgery for dislocation at 5 years old. Long-leg radiographs of the right leg showed 11° valgus mechanical angle., Discussion: After knowing the cause of the patellar dislocation from history taking, physical and supporting examination, we performed lateral open wedge distal femoral osteotomy also MPFL and MCL reconstruction, and tibial tuberosity medialization osteotomy. There is improvement mean score in Tegner Lysholm Knee Scoring system and IKDC Scoring at 6 months after surgery., Conclusion: Lateral open wedge distal femur osteotomy combine with MPFL and MCL reconstruction and tibial tuberosity medialization realignment procedure can be successfully done for improve irreducible patellar dislocation in valgus knee, from clinical and radiological evaluation have good outcome after surgery., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)

Background: Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent adult stem cells and have become an important source of cells for engineering tissue repair and cell therapy. Vascular endothelial growth factor (VEGF) promotes angiogenesis and contributes fibrous integration between tendon and bone during the early postoperative stage. Both MSCs and VEGF can stimulate cell proliferation, differentiation, and matrix deposition by enhancing angiogenesis and osteogenesis of the graft in the tunnel., Hypothesis: Injection of intratunnel BM-MSCs and VEGF enhances the early healing process of a tendon graft., Study Design: Controlled laboratory study., Methods: In this controlled animal laboratory study, each of 4 groups of rabbits underwent unilateral anterior cruciate ligament (ACL) reconstruction with use of the ipsilateral semitendinosus tendon. The rabbits received intratunnel injection of BM-MSCs and VEGF with a fibrin glue seal covering the distal tunnel at the articular site. Evaluation using magnetic resonance imaging (MRI), collagen type III expression, and biomechanical analyses were performed at 3- and 6-week intervals., Results: All parameters using MRI, collagen type III expression, and biomechanical analysis of pullout strength of the graft showed that application of intratunnel BM-MSCs and VEGF enhanced tendon-to-bone healing after ACL reconstruction., Conclusion: Intratunnel injections of BM-MSCs and VEGF after ACL reconstruction enhanced graft tunnel healing. Overall, the femoral tunnel that received BM-MSCs and VEGF had better advanced healing with increased collagen type III fibers and better outcomes on MRI and biomechanical analysis. MRI is the most reliable tool for clinical use in evaluating stages of ACL healing after reconstruction, since biopsy is an invasive procedure., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution.

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.