Functional, radiological, and quality of life outcome of unstable acetabular fracture with quadrilateral plate involvement at a tertiary care center in Jakarta, Indonesia.

INTRODUCTION: Unstable acetabular fracture remains a complex fracture that requires technically demanding surgery for orthopedic surgeons. Quadrilateral plate (QP) fractures of the acetabulum are a challenging group of acetabular fractures to manage. However, the literature regarding the management of these injuries are limited. The QP is a relatively thin medial wall of the acetabulum and intra-articular; thus, anatomical reduction and stable fixation are required for satisfactory outcome. This study aims to determine the functional, radiological, and quality of life outcome of unstable acetabular fracture with QP involvement. METHODS: This was a retrospective cohort study conducted at Cipto Mangunkusumo General Hospital during the period of 2010-2020. Patients with unstable acetabular fractures with and without QP involvement were included in this study. They were followed up postoperatively at 1, 6, and 12 months. Functional outcome was assessed using the Harris Hip Score (HHS), Merle D'Aubigne, and Oxford Hip Score (OHS); while radiology outcome was assessed using Matta Outcome Grading; and quality of life was assessed using the SF-36. RESULTS: This study involved 53 subjects with a median age was 29 (18-75) years of age. Twenty-eight (52.8%) subjects had unstable acetabular fracture with QP involvement. Twenty-five (47.2%) subjects had unstable acetabular fracture without QP involvement. Twenty-five (47.2%) subjects were fixed using quadrilateral hook plate, 3 (5.7%) with infrapectineal plate, 10 (18.8%) with posterior column plate, and 15 (28.3%) with suprapectineal plate. The median intraoperative bleeding in those with unstable acetabular fracture with QP involvement was 600 (300-4000) ml, which was higher than those without QP involvement (400 [100-1700] ml). Those with QP involvement achieved anatomical reduction in 20 (71.4%) subjects. Whereas, the subjects without QP involvement achieved anatomical reduction 23 patients (92%). Subjects with QP involvement had significantly lower functional, radiological, and quality of life outcomes compared to those without quadrilateral plate involvement based on Harris Hip Score (p = 0.046), Merle D'Aubigne (0.001), Oxford Hip Score (0.001), Matta Outcome Grading (0.004), and SF-36 (0.001). Patients with quadrilateral hook plate showed no significant functional, and radiological outcome difference compared to patients with infrapectineal plate based on Harris Hip Score (p = 0.582), Merle D'Aubigne (0.698), Oxford Hip Score (1.000), and Matta Outcome Grading (1.000). In addition, we also found no significant functional, radiological, and quality of life outcome difference between posterior column plate and suprapectineal plate group based on Harris Hip Score (p = 0.200), Merle D'Aubigne (0.643), Oxford Hip Score (0.316), Matta Outcome Grading (1.000), and SF-36 (0.600). CONCLUSIONS: Patients with unstable acetabular fracture with quadrilateral plate involvement subject had significantly lower functional, radiological, and quality of life outcomes compared to those without quadrilateral plate involvement. Both quadrilateral hook and infrapectineal plates demonstrated non-significant functional and radiological outcomes difference. Posterior column plate also resulted in the same functional, radiological, and quality of life outcome compared with suprapectineal fixation.

Analysis on association between sagittal stem alignment and early functional and radiological outcome following primary cementless total hip replacement.

INTRODUCTION: Accurate reconstruction of hip anatomy and biomechanics is mandatory for achieving good clinical outcomes following total hip replacement (THR). Optimal stem alignment is essential to avoid impingement or loosening. This study aimed to evaluate sagittal stem position following cementless THR and its relationship with patient's functional outcome and post-operative radiological parameters. METHOD: We performed analytical observational study with cross-sectional design on 71 hips (67 patients, ranged 18-85 years old) that underwent primary cementless THR in two orthopedic centers in Jakarta, Indonesia. All hips were operated through either anterolateral or posterior approach using either extended/full-coating wedge-tapered stem or proximal-coated wedge-tapered stem. Clinical outcomes were evaluated at follow-up time using mHHS questionnaire, VAS level of thigh pain, and hip ROM. Stem sagittal alignment and other radiological parameters, including combined anteversion and offset, were measured from conventional radiograph. RESULTS: There were no significant differences on mHHS score, VAS level on thigh pain, and ROM between stem alignment groups. Post-operative anteversion and offset of the implant were not affected by the stem sagittal position. All influencing factors have significant effect on sagittal stem alignment. Linear regression test on femur morphology showed 0.69° increase in stem posterior tilt for every 1° increase in the anterior bowing (coeff. = 0.502). CONCLUSION: Stem tilting in sagittal plane did not affect patient's functional outcome or post-operative radiological parameters. In addition, for every degree of increased anterior femoral bowing, 0.69° increase in posterior stem tilting can be expected.

Evaluation of adipose-derived stem cells (ASCS) exosome implantation and platelet-rich fibrin (PRF) on critical long bone defects in Sprague-Dawley rats.

INTRODUCTION: This study aimed to assess the efficacy of adipose-derived mesenchymal stem cell exosomes (ASCs exosome) and platelet-rich fibrin (PRF) in treating critical long bone defects in Sprague-Dawley rats. Critical long bone defects, defined as exceeding 2 cm or 50% of the bone diameter, often pose a healing challenge. While autologous bone grafts have been considered, they have shown unreliable results and donor-site complications, necessitating alternative treatments. METHODS: The research followed a quasi-experimental post-test only control group design involving 30 male Sprague-Dawley rats. The rats were divided into five groups and subjected to femur bone defect creation, internally fixed with a 1.4 mm K-wire, and treated with various combinations of hydroxyapatite (HA), bone graft (BG), ASCs exosome, and PRF. Histomorphometry and BMP-2 gene expression analysis were performed to evaluate bone healing. RESULTS AND DISCUSSION: The results indicated that the group treated with HA + BG + ASCs exosome (group IV) exhibited the highest BMP-2 gene expression, while group III (HA + BG + ASCs exosome + PRF) had the highest chordin level. Overall, groups receiving ASCs exosome or PRF intervention showed elevated BMP-2 expression compared to the control group. The use of ASCs exosome and PRF showed comparable outcomes compared to bone graft administration in terms of histomorphometry analysis. CONCLUSION: The administration of adipose tissue derived mesenchymal stem cells and PRF has a comparable outcome with the use of bone graft in terms of osseus area and expression of BMP-2 in critical bone defect.

Clinical evaluation of intralesional umbilical cord-derived mesenchymal stem cells, conditioned medium and triamcinolone acetonide injection for keloid treatment: A pilot study.

Topical keloid therapy is performed with triamcinolone acetonide (TA) intralesional injection. However, the recurrence rate is high with various side effects. Mesenchymal stem cells (MSCs) have high proliferative abilities and reduce the activity and proliferation of fibroblast cells in keloids. To overcome the costs and limitations, conditioned medium (CM) is used. This study aims to evaluate feasibility of intralesional injection of umbilical cord MSC (UC-MSC) and conditioned medium (UC-CM) compared to TA for keloid therapy. Twenty-four patients with keloids who met the inclusion criteria were included, randomized into three treatment groups and then got assessed for the sociodemographic data, keloid volume, histopathology (type 1:3 collagen ratio), interleukin-10 (IL-10) levels and Patient and Observer Scar Assessment Scale (POSAS) score during visits. Largest volume regression occurred in the UC-MSC group, followed by UC-CM and then the TA group (UC-MSC: 45.32% ± 2.61%; UC-CM: 43.61% ± 3.67%; TA: 28.34% ± 3.81%; p = 0.003). Similar pattern was also observed in increase in IL-10 levels, the decrease in POSAS scores and the reduction of type 1:3 collagen ratio. Hence, UC-MSC and UC-CM are promisingly more effective than TA for keloid therapy, showcasing their superiority in reducing keloid volume, symptoms and type 1:3 collagen ratio, as well as increasing the levels of IL-10.

Comparison of clinical outcomes between isolated ACL reconstruction and combined ACL with anterolateral ligament reconstruction: a systematic review and meta-analysis.

BACKGROUND: To compare the clinical outcomes between isolated cruciate ligament reconstruction (ACLR) and combined ACL with anterolateral ligament reconstruction in chronic ACL injury especially with rotary instability problem. METHODS: Systematic searches were conducted of literature published up to July 2021 on PubMed, Google Search, and Cochrane databases for studies comparing isolated ACLR and ACL with anterolateral reconstruction. Two reviewers independently determined eligibility, extracted outcome data, and assessed the risk of bias of eligible studies. Pooled clinical outcomes used random effects with mean differences and risk ratio for continuous and dichotomous variables, respectively. RESULTS: After excluding 49 articles based on full-text screening, six studies were identified which met the inclusion criteria in the meta-analysis. Clinical outcomes such as residual laxity, rotatory instability, and graft failure were compared between isolated ACLR and combined ACL and anterolateral stability reconstruction. Overall, both clinical outcomes of isolated ACL and combined ACL with anterolateral reconstruction show improvement results in pivot shift test, the absence of residual laxity and incidence of graft failure. Compared to isolated ACLR, the prominent postoperative result was by combined ACL with anterolateral reconstruction which had significant differences in laxity outcome based on (I2 = 89%, p < 0.00001) and (MD = 0.71, 95%CI: 0.33-1.08, p = 0.00002). CONCLUSIONS: The combined ACL with anterolateral reconstruction tended to have superior clinical outcomes, especially in the absence of residual laxity, compared to the isolated ACLR, but the other results were not significantly different statistically. Combined ACL and anterolateral reconstruction were not performed routinely for patients undergoing ACL reconstruction, but more suitable for chronic rotatory instability problem.

Allogeneic umbilical cord mesenchymal stem cell conditioned medium (secretome) for treating posterior cruciate ligament rupture: a prospective single-arm study.

BACKGROUND: Outcomes of the current management of posterior cruciate ligament (PCL) rupture are still unsatisfactory. Recent literature demonstrated the efficacy of the paracrine action of mesenchymal stem cells (MSC) in ligament rupture healing. This study aimed to evaluate the outcome of arthroscopic administration of allogeneic umbilical cord-derived MSC (UC-MSC) conditioned medium (secretome) for the treatment of PCL rupture. PATIENTS AND METHODS: This is a prospective study including 12 individuals with PCL rupture grade 1 or 2 who were performed arthroscopy and secretome administrations. The functional and radiologic outcome of the knee was examined one year following intervention. RESULTS: Preoperatively, posterior drawer test revealed three cases of grade 2+ and nine cases of grade 1+, whereas the final follow-up revealed two cases of grade 2+ and ten cases of grade 1+ PCL rupture. At final follow-up, the mean scores for the IKDC, modified Cincinnati, and Lysholm were 90.58 ± 4.30, 90.90 ± 2.15, and 89.42 ± 3.16, respectively. The means of the serial hop tests were 90.33, 94.16, 93.66, and 95.33 for single, triple, crossover, and time hop tests, respectively. Five patients were able to resume competitive sport after an average of 25.8 weeks (25-38). The final MRI analysis revealed that six knees (50%) regained PCL continuity with low signal intensity, five knees (41.6%) returned near-normal PCL continuity, and one knee (8.3%) regained PCL continuity but with deformed outlines. CONCLUSIONS: Short-term follow-up indicated that the secretome generated from allogenic UC-MSC produces excellent functional and radiographic results in grade I-II PCL rupture.

Umbilical cord mesenchymal stem cells combined with secretome for treating congenital pseudarthrosis of the Tibia: a case series.

INTRODUCTION: Most patients with congenital pseudoarthrosis of tibia (CPT) do not have promising outcomes despite multiple attempts using conventional surgeries. The combination of umbilical cord-derived mesenchymal stem cells and conditioned medium (secretome) contains major components pivotal for the enhancement of fracture healing. The purpose of this study was to address fracture healing in CPT cases that were treated using the combined implantation of umbilical-cord mesenchymal stem cells (UC-MSCs) and secretome. MATERIALS AND METHODS: From 2016 to 2017, six patients with CPT who were treated by one senior pediatric orthopedic consultant at a single center (3 girls and 3 boys; mean age of 5.8 years) were included in this case series. A combined procedure including resection of hamartomatous fibrotic tissue, implantation of MSCs and secretome, and fixation using a locking plate and screws was performed. Patients were followed up for a mean of 29 months. Leg-length discrepancy, refracture rate, functional outcome, and radiological outcomes were assessed preoperatively, immediately postoperatively and at the final follow-up. RESULT: Five out of 6 (83%) of the patients experienced primary union. One patient experienced refracture; however, 8 months later, after another implantation and reconstruction were performed, union eventually occurred. Significant functional improvement was achieved after at least 1 year of follow-up. CONCLUSION: This case series suggests that the combination of secretome and UC-MSCs is a potential treatment for CPT, it highlights the efficacy of the combined procedure in treating CPT and in achieving satisfying results. A larger number of subjects and longer follow-up are required for further study.

The management of pelvic ring fractures in low-resource environments: review.

Although improvement of pelvic trauma care has been successful in decreasing mortality rates in major trauma centers, such changes have not been implemented in low-resource environments such as low-middle-income countries (LMICs). This review details the evaluation and management of pelvic ring fractures and recommends improvements for trauma care in low-resource environments. Prehospital management revolves around basic life support techniques. Application of non-invasive pelvic circumferential compression devices, such as bed sheet or pelvic binders, can be performed as early as the scene of the accident. Upon arrival at the emergency department, rapid clinical evaluation and immediate resuscitation should be performed. Preperitoneal pelvic packing and external fixation devices have been considered as important first-line management tools to achieve bleeding control in hemodynamically unstable patients. After patient stabilization, immediate referral is mandated if the hospital does not have an orthopedic surgeon or facilities to perform complex pelvic/acetabular surgery. Telemedicine platforms have emerged as one of the key solutions for informing decision-making. However, unavailable referral systems and inaccessible transportation systems act as significant barriers in LMICs. Tendencies toward more "old-fashioned" protocols and conservative treatments are often justified especially for minimally displaced fractures. But when surgery is needed, it is important to visualize the fracture site to obtain and maintain a good reduction in the absence of intraoperative imaging. Minimizing soft tissue damage, reducing intraoperative blood loss, and minimizing duration of surgical interventions are vital when performing pelvic surgery in a limited intensive care setting.

Double-bundle ACL reconstruction versus anatomic single-bundle ACL reconstruction combined with anterolateral ligament reconstruction: a comparative study of clinical outcome.

INTRODUCTION: Recent studies showed increasing evidences of anterolateral ligament (ALL) reconstruction in conjunction with anterior cruciate ligament (ACL) reconstruction that proves to be more superior to the previous double-bundle (DB) ACLR technique especially in improving knee stability in biomechanic studies. However to date, there have been no studies evaluating the functional outcome of DB-ACLR vs single-bundle (SB) with ALL in ACLR. METHODS: A total of 138 patients with ACL deficient knee were enrolled to the study. Double-bundle ACL reconstruction (DB-ACLR) was performed in 75 patients and single-bundle ACL reconstruction with anterolateral ligament reconstruction (SB + ALL) ACLR was performed in 63 patients. Surgical outcomes were compared with The International Knee Documentation Committee Subjective Knee Form (IKDC) and the Kujala score at the 3rd, 6th and 9th month post-operative. RESULTS: The IKDC score in the 3rd and 6th month was superior in the SB + ALL group compared to the DB group. However, this difference was not statistically significant. In the meantime, there were no statistically significant difference between the Kujala Score at the 3rd, 6th, and 9th months consecutively. There were no statistically significant differences in the functional outcomes of DB-ACLR and SB + ALL groups at the 3rd, 6th, and 9th months post-operative period. CONCLUSION: The functional outcome comparison showed non-superiority of SB + ALL group compared to the DB-ACLR group. The patellar pain was less found in DB-ACLR group at 6- and 9-months post-operative period.

Management of pelvic ring fractures in limited resources country: a retrospective study.

PURPOSE: Pelvic ring fractures (PRFs) management needs adequate facilities and human resources. However, the prehospital ambulance management role in Indonesia is insufficient. Many hospitals have limited resources that necessitate patients to be referred to higher trauma centers. This study aims to describe the state of PRFs management at a level 1 trauma center in limited-resource country. METHODS: We conducted retrospective studies of PRFs management from 2011 to 2021 at Cipto Mangunkusumo Hospital. We analyzed patient's management flow from injury, referral process, initial to definitive treatment, mortality, and Majeed functional score. RESULTS: From 109 patients, 30.3% were non-referrals that came without ambulance, while 69.7% were referrals using an ambulance. All non-referral patients came without pelvic binder with 54.5% unstable hemodynamic, while 35.5% of the referrals came with unstable hemodynamic and 72.4% had pelvic binder. Median time for non-referrals reaching our hospital is 12.5 h. Unlike local referrals, 75% of regional and 85.7% of national referrals general improvement had to be improved before being referred. Polytrauma cases were 33.9% with 12 days mean interval to definitive treatment. Mortality rate in this study was 13.8%. During post-operative follow-up with a mean of 4 years, 83% of patients could be followed up and reported 93 median Majeed score. CONCLUSION: The management of PRFs at level 1 trauma center in limited-resource country shows a mortality rate of 13.8% through various limitations such as unimplemented ambulance prehospital management, number of patients who were referred without pelvic binder applied, and the long waiting interval for definitive treatment.

The Banff Patellar Instability Instrument: validity and reliability of an Indonesian version.

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.

The Role of Interleukin 10 in Keloid Therapy: A Literature Review.

INTRODUCTION: Keloids are pathological wound healing responses to dermal injuries. These scars may lead to considerable morbidity, but treatments remain challenging for physicians. Interleukin 10 (IL-10), a potent anti-inflammatory cytokine, plays a prominent role in fetal scarless regenerative healing; therefore, it may become a more targeted and effective therapy for keloids. This review aimed to obtain an overview of the background of keloid and IL-10 functions as its promising forthcoming treatment. MATERIALS AND METHODS: Studies were sought from Pubmed, ScienceDirect, PLOS, and Clinical Key. Keywords are interleukin 10, keloid, and wound healing as Medical Subject Headings terms. RESULTS AND DISCUSSION: Keloids and fetal scarless healing represent 2 opposing ends of the tissue repair spectrum. Promising multiple animal models have demonstrated successful regenerative healing promotion through IL-10 overexpression by its ability to minimize inflammatory wound microenvironment, downregulate transforming growth factor ß/SMAD signaling pathway, increase extracellular matrix breakdown, and regulate extracellular matrix. These results have led to the development of clinical trials investigating human recombinant IL-10. CONCLUSIONS: Interleukin 10 has the potential to become a more targeted and promising therapy of keloids owing to its pleiotropic effects.

Oral L-arginine supplementation for fracture healing: a systematic review of preclinical studies.

Introduction: Approximately 5 to 10% of all patients with fractures experience deficient fracture healing that results in fracture nonunions. Previous studies have shown that nitric oxide production from arginine could improve fracture healing by improving local blood supply, supplementing growth factors, and improving collagen synthesis. Apart from its simple oral mode of administration, this amino acid provides a non-toxic and inexpensive option for fracture healing. To date, no systematic reviews regarding oral L-arginine supplementation for fracture healing are available. We present the first systematic review of oral L-arginine supplementation for fracture healing. Methods: A systematic literature search was carried out using PubMed, Google Scholar, and ScienceDirect until February 1, 2021 using a combination of text words. No date limits were set. Studies investigating the use of oral L-arginine supplementation for fracture healing were included. Reference lists of relevant publications were assessed for additional references. In addition, bibliographies from other reviews were searched. Results: Four studies were included. Of these, 3 were animal studies, and the other one was an in vitro study. Animals that were given oral L-arginine supplementation had significantly increased angiogenesis, reduced defect area, higher osteoblasts and osteoclasts, and higher rate of bone formation compared to controls. Conclusions: The available preclinical studies suggest that oral L-arginine supplementation is a potential new therapy for fracture healing. This amino acid supplement is not only affordable and non-toxic; it is also simple. Further clinical studies are required to investigate the optimal dose of oral L-arginine supplementation for fracture healing in human subjects.

Allogeneic umbilical cord-derived mesenchymal stem cells for treating critical-sized bone defects: a translational study.

INTRODUCTION: The current 'gold-standard' treatment of critical-sized bone defects (CSBDs) is autografts; however, they have drawbacks including lack of massive bone source donor site morbidity, incomplete remodeling, and the risk of infection. One potential treatment for treating CSBDs is bone marrow-derived mesenchymal stem cells (BM-MSCs). Previously, there were no studies regarding the use of human umbilical cord-mesenchymal stem cells (hUC-MSCs) for treating BDs. We aim to investigate the use of allogeneic hUC-MSCs for treating CSBDs. METHOD: We included subjects who were diagnosed with non-union fracture with CSBDs who agreed to undergo hUC-MSCs implantation. All patients were given allogeneic hUC-MSCs. All MSCs were obtained and cultured using the multiple-harvest explant method. Subjects were evaluated functionally using the Lower Extremity Functional Scale (LEFS) and radiologically by volume defect reduction. RESULT: A total of seven (3 male, 4 female) subjects were recruited for this study. The subjects age ranged from 14 to 62 years. All seven subjects had increased LEFS during the end of the follow-up period, indicating improved functional ability. The follow-up period ranged from 12 to 36 months. One subject had wound dehiscence and infection, and two subjects developed partial union. CONCLUSION: Umbilical cord mesenchymal stem cells are a potential new treatment for CSBDs. Additional studies with larger samples and control groups are required to further investigate the safety and efficacy of umbilical cord-derived mesenchymal stem cells for treating CSBDs.

Umbilical cord-derived mesenchymal stem cells for treating osteoarthritis of the knee: a single-arm, open-label study.

BACKGROUND: Despite being a common cause of quality-of-life impairment, there are no efficacious therapies that could prevent the progression of knee osteoarthritis (KOA). We conducted an open-label trial of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and hyaluronic acid (HA) for treating KOA. METHODS: This open-label study was conducted from July 2015 to December 2018 at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Patients diagnosed with KOA were injected three times, comprising of 10 × 106 units of hUC-MSCs in 2-ml secretome implantation and 2-ml hyaluronic acid (HA) injection in the first week, followed with 2-ml HA injection twice in the second and third week. RESULTS: Twenty-nine subjects (57 knees) were recruited. Seventeen (58.6%) subjects were male, and the mean age was 58.3 ± 9.6 years. Thirty-three (57.9%) knees were classified into Kellgren-Lawrence grade I-II KOA (mild OA). hUC-MSCs significantly decreased pain measured by visual analogue scale in severe KOA from initial to 6th month follow-up [5 ± 2.97 to 3.38 ± 2.44 (p = 0.035)]. The International Knee Documentation Committee score significantly increased at 6th month follow-up (53.26 ± 16.66 to 65.49 ± 13.01, p < 0.001, in subjects with grade I-II and 48.84 ± 18.41 to 61.83 ± 18.83, p = 0.008, in subjects with severe KOA). The Western Ontario and McMaster Universities Osteoarthritis decreased significantly in both groups from initial to 6th month follow-up (from 22.55 ± 15.94 to 13.23 ± 10.29, p = 0.003, and from 27.57 ± 15.99 to 17.92 ± 19.1, p = 0.003, in those with mild and severe KOA, respectively). CONCLUSIONS: hUC-MSCs could be a potentially new regenerative treatment for KOA. The maximum effect of hUC-MSCs was achieved after 6 months of injection. LEVEL OF EVIDENCE: Therapeutic level II.

Autologous mesenchymal stem cell implantation, hydroxyapatite, bone morphogenetic protein-2, and internal fixation for treating critical-sized defects: a translational study.

INTRODUCTION: Critical-sized defect (CSD) is one of the most challenging cases for orthopaedic surgeons. We aim to explore the therapeutic potential of the combination of bone marrow-derived mesenchymal stem cells (BM-MSCs), hydroxyapatite (HA) granules, bone morphogenetic protein-2 (BMP-2), and internal fixation for treating CSDs. METHODS: This was a translational study performed during the period of January 2012 to 2016. Subjects were patients diagnosed with CSDs who had previously failed surgical attempts. They were treated with the combination of autologous BM-MSCs, HA granules, BMP-2, and mechanical stabilization. Post-operative pain level, functional outcome, defect volume, and radiological healing were evaluated after a minimum follow-up of 12 months. RESULTS: A total of six subjects were recruited in this study. The pain was significantly reduced in all cases; with the decrease of mean preoperative visual analog scale (VAS) from 4 ± 2.2 to 0 after six month follow-up. Clinical functional outcome percentage increased significantly from 25 ± 13.7 to 70.79 ± 19.5. Radiological healing assessment using Tiedemann score also showed an increase from 0.16 ± 0.4 to 8 ± 3 at one year follow-up. No immunologic nor neoplastic side effects were found. CONCLUSIONS: The combination of autologous BM-MSCs, HA granules, and BMP-2 is safe and remains to be a good option for the definitive treatment for CSD with previous failed surgical attempts. Further studies with a larger sample size are required to be done.

Scoliocorrector Fatma-UI for correction of adolescent idiopathic scoliosis: Development, effectivity, safety and functional outcome.

BACKGROUND: Adolescent idiopathic scoliosis remains a major problem due to its high incidence, high risk, and high cost. One of the aims of the management in scoliosis is to correct the deformity. Many techniques are available to correct scoliosis deformity; however, they are all far from ideal to achieve three-dimensional correction in scoliosis. AIM: To develop a set of tools named Scoliocorrector Fatma-UI (SCFUI) to aid three-dimensional correction and to evaluate the efficacy, safety, and functional outcome. METHODS: This study consists of two stages. In the first stage, we developed the SCFUI and tested it in finite element and biomechanical tests. The second stage was a single-blinded randomized clinical trial to evaluate the SCFUI compared to direct vertebral rotation (DVR). Forty-four subjects with adolescent idiopathic scoliosis were randomly allocated into the DVR group (n = 23) and SCFUI group (n = 21). Radiological, neurological, and functional outcome was compared between the groups. RESULTS: Finite element revealed the maximum stress of the SCFUI components to be between 31.2 - 252 MPa. Biomechanical analysis revealed the modulus elasticity of SCFUI was 9561324 ± 633277 MPa. Both groups showed improvement in Cobb angle and sagittal profile, however the rotation angle was lower in the SCFUI group (11.59 ± 7.46 vs 18.23 ± 6.39, P = 0.001). Neurological and functional outcome were comparable in both groups. CONCLUSION: We concluded that SCFUI developed in this study resulted in similar coronal and sagittal but better rotational correction compared to DVR. The safety and functional outcomes were also similar to DVR.

A Novel Diabetic Arthritic Model in Rats Induced by Streptozotocin, High-Fat Diet, and Complete Freund's Adjuvant.

Introduction: Ankle arthrodesis is one of the treatments of choice, particularly in late-stage and unstable diabetic Charcot arthropathy. Unfortunately, poor healing capacity might play a role in the high nonunion rate (10-40%). The advancement in regenerative medicine opens a new horizon for enhancing fusion after ankle arthrodesis in patients with poor healing capacity. However, a suitable small animal model is warranted to study the effectivity of these regenerative medicine approaches. Streptozotocin (STZ)-induced diabetes models and adjuvant-induced arthritis models with complete Freund's adjuvant are two established models. However, no study has combined those two models to make a diabetic arthritic model that more closely resembles the condition in Charcot arthropathy. Methods: Twenty male Sprague-Dawley rats were assigned into five groups, consisting of one control group, and four diabetic groups which were induced by STZ injection and a high-fat diet. Among these diabetic rats, two groups received complete Freund's adjuvant (CFA) injections to the left ankle of the hind limb. The control group, one of the diabetic-only groups, and one of the arthritic-diabetic-induced groups were euthanized at 4 weeks after STZ induction, and the remainder were euthanized 6 weeks after STZ induction. Clinical, radiological, and histological examinations were then compared in all five groups. Results: Diabetic status was successfully achieved in the model, which was maintained until the completion of the study. The CFA-induced ankles were significantly larger than the contralateral ankles in all groups (p<0.05). Histopathological evaluation confirmed arthritic changes in the CFA-induced group with less variability after 4 weeks of arthritis induction. Conclusion: This rat model of arthritic diabetic mimics the progressive and chronic nature of Charcot arthropathy in humans. This model can be further use to study treatments that might enhance the fusion rate in ankle arthrodesis in healing-defective patients such as those with diabetes. Level of Clinical Evidence: 5.

Modified Mesenchymal stem cell, platelet-rich plasma, and hyaluronic acid intervention in early stage osteoarthritis: A systematic review, meta-analysis, and meta-regression of arthroscopic-guided intra-articular approaches.

BACKGROUND: Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid (HA). This study aimed to assess the synergy of MSCs, PRP, and varying HA doses, and determine optimal MSC sources to treat early-stage OA in the perspective of Lysholm score, VAS Score, KSS score, and WOMAC score. METHOD: Original articles from 2013 to 2023 were screened from four databases, focusing on clinical trials and randomized controlled trials. The Risk of Bias in Non-randomized Studies-of Interventions (ROB-2) tool evaluated bias, and a PICOS criteria table guided result construction. Revman 5.4 analyzed outcomes such as Lysholm score, VAS score, KSS, WOMAC score, cartilage volume, and defect size using MRI. This systematic review adhered to PRISMA guidelines. RESULT: Nine studies met the final inclusion criteria. Meta-analysis revealed a significant improvement in Lysholm score (MD: 17.89; 95% CI: 16.01, 19.77; I2 = 0%, P = 0.56), a notable reduction in VAS score (MD: -2.62; 95% CI: -2.83, -2.41; I2 = 99%, P < 0.00001), elevated KSS (MD: 29.59; 95% CI: 27.66, 31.52; I2 = 95%, P < 0.0001), and reduced WOMAC score (MD: -12.38; 95% CI: -13.75, -11.01; I2 = 99%, P < 0.0001). CONCLUSIONS: Arthroscopic guided high-dose subchondral application of primary cultured synovial MSCs in popliteal PRP media with HA effectively regenerates cartilage defects and improves clinical outcomes in early-stage osteoarthritis. Clarification of MSC sources and quantities enhances the understanding of this promising treatment modality.

TBX3 transfection and nodal signal pathway inhibition promote differentiation of adipose mesenchymal stem cell to cardiac pacemaker-like cells.

BACKGROUND: Mesenchymal stem cells (MSCs) are known as one of the best candidate cells to produce cardiac pacemaker-like cells (CPLCs). Upregulation of TBX3 transcription factor and inhibition of the nodal signal pathway have a significant role in the formation of cardiac pacemaker cells such as sinoatrial and atrioventricular nodes, which initiate the heartbeat and control the rhythm of heart contractions. This study aimed to confirm the effects of transfection of TBX3 transcription factor and inhibition of the nodal signal pathway on differentiating adipose-derived MSCs (AD-MSCs) to CPLCs. AD-MSCs were characterized using flow cytometry and three-lineage differentiation staining. METHODS: The transfection of TBX3 plasmid was carried out using lipofectamine, and inhibition of the nodal signal pathway was done using the small-molecule SB431542. The morphology of the cells was observed using a light microscope. Pacemaker-specific markers, including TBX3, Cx30, HCN4, HCN1, HCN3, and KCNN4, were evaluated using the qRT-PCR method. For protein level, TBX3 and Cx30 were evaluated using ELISA and immunofluorescence staining. The electrophysiology of cells was evaluated using a patch clamp. RESULTS: The TBX3 expression in the TBX3, SM, and TBX + SM groups significantly higher (p < 0.05) compared to the control group and cardiomyocytes. The expression of Cx40 and Cx43 genes were lower in TBX3, SM, TBX + SM groups. In contrast, Cx30 gene showed higher expression in TBX3 group. The expression HCN1, HCN3, and HCN4 genes are higher in TBX3 group. CONCLUSION: The transfection of TBX3 and inhibition of the nodal signal pathway by small-molecule SB431542 enhanced differentiation of AD-MSCs to CPLCs.