PENGARUH PEMBERIAN PLATELET-RICH FIBRIN DAN ALLOGENIC MESENCHYMAL STEM CELLS TERHADAP EKSPRESI PAX-7 DAN MYO-D PADA PENYEMBUHAN MODEL CEDERA OTOT GASTROCNEMIUS NEW ZEALAND WHITE RABBIT

Latar Belakang: Cedera otot adalah cedera yang paling sering terjadi saat melakukan aktivitas olahraga. Restorasi kapasitas fungsional otot seringkali tidak terjadi secara sempurna, dan juga memakan waktu proses yang lama. Penggunaan platelet-rich fibrin (PRF) dan muscle-derived allogeneic mesenchymal stem cells (AMSC) dapat meningkatkan efisiensi penyembuhan luka. Hal ini akan ditunjukkan dengan ekspresi Pax7 dan MyoD dalam aktivasi sel satelit dan diferensiasi sel otot. Metode Penelitian: Penelitian dilakukan secara true experimental dengan rancangan randomized post test only with control group menggunakan data primer berupa evaluasi klinis dan immunohistopatologi dari model cedera otot gastrocnemius kelinci New Zealand White Rabbit yang diberikan PRF, AMSC, dan kombinasi keduanya. Hasil yang didapatkan berupa angka rerata immunoreactive score ekspresi Pax7 dan MyoD. Hasil: Didapatkan perbedaan yang bermakna untuk angka rerata skor ekspresi Pax7 minggu antara kelompok perlakuan (p=0,009) dan minggu keempat (p=0,017). Hasil minggu kedua, Kelompok kontrol 5,6±0,484; PRF 6,69±0,388 (p=0,036); AMSC 6,648±0,562 (p=0,046); dan kombinasi 6,94±0,776 (p=0,009). Hasil minggu keempat, kelompok kontrol 7,62±0,94; PRF 8,97±0,61 (p=0,077); MSC 8,99±0,51 (p=0,072); dan kombinasi 9,39±1,02 (p=0,015). Terdapat perbedaan yang bermakna untuk angka rerata skor ekspresi MyoD minggu antara kelompok perlakuan (p=0,005) dan minggu keempat (p=0,022). Hasil minggu kedua, Kelompok kontrol 6,07±0,89; PRF 8,212±0,82 (p=0,009); AMSC 7,89±0,95 (p=0,028); dan kombinasi 8,216±0,97 (p=0,009). Hasil minggu keempat, kelompok kontrol 9,07±0,26; PRF 9,79±0,71 (p=0,130); MSC 9,83±0,41 (p=0,106); dan kombinasi 10,13±0,42 (p=0,016). Kesimpulan: Terdapat peningkatan ekspresi Pax7 dan MyoD pada model cedera otot yang diberikan PRF, AMSC, dan kombinasi. Peningkatan ekspresi tertinggi dicapai pada kelompok kombinasi

The role of platelet-rich fibrin facilitates the healing of gastrocnemius muscle defect: a preliminary study on animal model

Background: Scar formation has been a classical issue in the healing of skeletal muscle defect which will results in decrease of strength and function. Platelet-rich plasma (PRP) has been studied to enhance the healing of muscle defect. The disadvantages of it include the risk of immunologic reaction, time-consuming preparation, and lack of scaffold element. Platelet-rich fibrin (PRF) is a new generation of platelet concentrate that provides good source of growth factors and scaffold element necessary for the healing. This study is to provide a fondation of PRF preparation and implantation for the healing of experimental defect of gastrocnemius muscle in an animal model. Purpose: The goal is to provide a fondation of PRF preparation and implantation for the healing of experimental defect of gastrocnemius muscle in an animal model. Methods: Animal Care and Use Committee, Airlangga University approved the study. Twenty New Zealand white rabbits were divided into two groups. In control group, a defect was created in the right gastrocnemius and no implantation was done. In study group, similar defect was created with implantation of PRF. Two and four weeks after surgery, the defect was examined immunohistochemically for the expression of Pax7 protein. Results: The implanted group showed higher IRS score in two and four weeks compared to the control group. Conclusion: The use of PRF facilitates the healing of muscle injury. This study will be used as a fondation for further study on PRF

Comparison of functional outcome after early and delayed anterior cruciate ligament reconstruction: A systematic review

 This study aims to find the optimal timing for Anterior Cruciate Ligament (ACL) reconstruction by comparing the outcome of early versus delayed ACL reconstruction, meniscus, and chondral damage. A systematic literature search was performed from February to March 2021 from 4 databases. Inclusion criteria were English language Randomized Control Trial (RCT) and observational studies published in 2000-2020, 20-50 years old patients with an isolated ACL tear with/without meniscal injury underwent ACL reconstruction. Early ACL reconstruction was estimated at less than six weeks post-injury, and delayed ACL reconstruction was estimated at more than six weeks. Tegner and Lysholm were the functional outcomes to compare early and delayed ACL reconstruction with a meniscus tear and chondral damage. The search yielded 3094 studies. After removing duplicates, titles and abstracts were screened, leaving 154 potential studies. The studies were selected, and eight studies were eligible. No statistically significant difference between early and delayed ACL reconstruction in Lysholm and Tegner score (p>0,05) was found. Both scores were similar regarding whether the patient performs early/delayed ACL reconstruction. Therefore, early ACL reconstruction could be an optimal timing for the patient who will undergo ACL reconstruction

Combination of bone marrow aspirate, cancellous bone allograft, and platelet-rich plasma as an alternative solution to critical-sized diaphyseal bone defect: A case series

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

Correction of severe valgus deformity of knee osteoarthritis with non-constrained total knee arthroplasty implant: A case report

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

Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells as an Alternative Cell Source for Cell-based Osteoarthritis Treatment: A Systematic Review on Preclinical and Clinical Evidence

ABSTRACT Introduction: There is still no definitive treatment to either inhibit the degradation process or restore the damaged cartilage in osteoarthritis (OA). Various cell sources have been studied and in vitro studies showed that infrapatellar fat pad-derived mesenchymal stem cells (IFPDMSCs) exhibit higher chondrogenic potential than other adipose-derived cells. Still, very few in vivo studies on IFPDMSCs for cartilage healing in OA have been reported. Aims: This systematic review will analyze the therapeutic potential of IFPDMSCs for cartilage healing in osteoarthritis from preclinical and clinical studies. Design, Methods, and Data Source: Using the PubMed, EMBASE, and Cochrane Library database up to November 30, 2020, a systematic review according to PRISMA reporting guideline was conducted on IFPDMSCs application to treat osteoarthritis in vivo studies. Inclusion criteria were in vivo preclinical and clinical studies from January 2010 to November 2020 involving the OA model or cases using IFPDMSCs to promote healing. Results: In vivo studies are scarce. Only four studies are included: two animals and two clinical studies. All included studies demonstrate favourable results of IFPDMSCs in osteoarthritis, but there is heterogeneity in outcome measurement among all studies. Conclusion: The in vitro and currently limited in vivo studies showed that infrapatellar fat pad-derived mesenchymal stem cells offer an alternative cell source with promising chondrogenic healing potential. Impact: More preclinical and clinical in vivo studies should be encouraged to explore and support the efficacy of IFPDMSCs in cell-based OA treatment to prove the promising result as those of the in vitro studies

Physiobiochemical and microbiologic stability characteristics of freeze-dried cartilage secretome Adipose Mesenchymal Stem Cell (AdMSC)

Cartilage is an avascular, alymphatic, and aneurysmal structure, so it is difficult to heal properly if an injury occurs. Using Chondrogenic Adipose Mesenchymal Stem Cell (AdMSC) secretome as an adjuvant is one of the therapeutic options to overcome the problem of injury to the cartilage. Storage and distribution problems must be solved if we use this method. This study aims to characterize the Freeze-dried chondrogenic AdMSC secretome.  Secretome's physical, biochemistry, and microbiology stability are derived from the chondrogenic AdMSC secretome. This study’s design is prospective observational analytics research. Freeze-dried cartilage secretome AdMSC was analyzed for physical (organoleptic changes (shape, color, and odor), pH, biochemistry (TGF-β3), and microbiology (microbe contamination) stability. The difference was observed in 0, 4, 8, and 12 weeks. Data normality and homogeneity were tested using the Shapiro-Wilk test and followed up with the Friedman and Wilcoxon tests to analyze the data further. Organoleptics change showed no color change until four weeks with no change of shape and smell until 12 weeks. No significant difference was found in porosity and pH change—TGF-β3, which has a role in chondrogenesis, has no considerable decrease until 12 weeks. No contamination was found until 12 weeks

Excellent Result of Revision Total Hip Replacement with Unexpected Metallosis

ABSTRACT Background: Metallosis is a syndrome of metal-induced synovitis with infiltration and accumulation of metallic debris into the periprosthetic structures, including soft and bony tissues. The debris causes a chronic inflammatory reaction due to joint instability, pain, osteolysis, implant loosening, or implant failure. The absence of a specific sign or symptom that indicates metallosis causes difficulty to diagnose. Presentation of Case: A 35-year-old female, history of primary left total hip replacement since seven years ago after avascular necrosis of the femoral head, presented with an eight-month history of left hip pain and limited range of motion. Radiograph results showed that there is no evidence of periprosthetic fracture or infection. The patient underwent a left revision total hip replacement, which revealed extensive necrotic black metal debris throughout the joint space. Discussion: Effective treatment requires a revision of total hip replacement to remove metal debris, bone graft area osteolysis, and to address the mechanical failure. The greatest possible of metallic debris during debridement is vital to avoid further osteolysis and prevent more extensive damage. Excellent clinical result was evaluated by Harris’s hip score in 18 months postoperatively. Conclusion: This case is a rare example of chronic metallosis presenting seven years following total hip replacement. Revision total hip replacement is the consensus management choice to avoid further destruction of the bone and joint capsule that can occur with metal-induced inflammation

Lengthening of Massive Intercalary Cortical Allograft After Successful Graft Incorporation in Skeletally Immature Bone with Critical-Sized Defect: A Case Report with 6-year Follow-up

Bone allograft serves as an alternative to overcome the limitation of autograft. Some concerns, such as graft rejection, infection, and low union rate, arise from the use of bone allograft since the graft is a non-living and foreign material. We reported a case of critical-sized bone defect in a skeletally immature patient treated with massive intercalary allograft that not only did it show union but also graft incorporation that allowed for subsequent bone lengthening at the site of the incorporated massive allograft. To our knowledge, there has been a report of lengthening of free-vascularized fibular autograft but not the nonvascularized one. Massive intercalary allograft that incorporates well to the host could be an option to treat critical-sized bone defect

Analysis of prognostic factors in soft tissue sarcoma: Cancer registry from a single tertiary hospital in Indonesia. A retrospective cohort study

Background Soft tissue sarcoma is one cause of mortality in adult malignancies. This tumor is rare, persistent, and highly-recurrent. Many patients are came in late stage. It is important to identify a prognostic tool that is reliable, easily obtainable, and widely applicable. The aim of this study is to investigate and analyze the prognostic value of clinicopathological and biomarker factors in patients with soft tissue sarcoma. Methods This retrospective study extracts data from the musculoskeletal tumor registry from January 2012 to December 2018 in a single tertiary hospital. Eighty patients with diagnosis of soft tissue sarcoma were included. Preoperative modified Glasgow Prognostic Score, Neutrophils/Lymphocytes Ratio, Hemoglobin, serum lactate dehydrogenase data were analyzed along with demographic, clinical, radiological and histopathological data. The relationship between variables on overall survival, distant metastasis, and local recurrence were evaluated using univariate and multivariate Cox regression. Results On univariate analysis, there was significant relationship between hemoglobin, Neutrophils/Lymphocytes Ratio and modified Glasgow Prognostic Score with overall survival (p = 0.031, HR = 1.99; p = 0.04, HR = 1.129; and p = 0.044, HR = 3.89). A significant relationship was found between age and soft tissue sarcoma stage with distant metastasis (p = 0.046, HR = 1.95; and p = 0.00, HR = 3.22). In addition, we also found significant relationship between surgical margin with local recurrence (p = 0.018, OR = 3.44). However, on multivariate analysis the independent prognostic factor for overall survival was only modified Glasgow Prognostic Score (HR = 2.138; p = 0.011). Stage IIIA (HR = 5.32; p = 0.005) and IIIB (HR = 13.48; p = 0.00) were independent prognostic for distant metastasis. Surgical margin was independently associated with local recurrence (HR = 14.84; p = 0.001). Conclusion Modified Glasgow Prognostic Score can be used as prognostic tool of overall survival in soft tissue sarcoma patients. Moreover, stage of STS and surgical margin can be used as a prognostic factor for distant metastasis and local recurrence of soft tissue sarcoma respectively