Bone implants are important in the recovery of fractures and degenerative diseases. Although many implants have been marketed, study on Indonesian-made plates is still limited. The aim of this study was to assess the patients' functional and radiological improvements and biomechanical and chemical changes of Indonesian-made plates used in long bone fractures. retrospective study was conducted at Semen Gresik Hospital, Gresik, Indonesia. This study included adult patients with long bone fractures who had surgeries with Indonesian plates. Functional improvement (assessed using disabilities of arm, shoulder, and hand (DASH) or lower extremity functional scale (LEFS)) and radiological data (assessed using radiographic union score (RUS)) were assessed in week 4 and month 6, 12, and 15 after surgery. Biomechanical changes (hardness and roughness test) and chemical analysis were assessed after 15 months of use. The normality of the data was tested with Shapiro-Wilk while data analysis was conducted using paired Student t-test or Friedman test as appropriate with type of data. Our data indicated that the DASH and LEFS functional scores had significant improvement over the follow-ups indicating functional recovery. RUS scores also improved over time, indicating a good healing process. Hardness tests on post-surgery implants showed a decrease in hardness of 7.3% and an increase of 3.3% in roughness. Chemical analysis showed a reduction in chemical levels in the implant of 7.8%, indicating durability and minimal toxicity. This study highlights that Indonesian implants have been proven safe to use in fractures. Further examinations with a larger sample and a longer duration of monitoring are recommended for stronger validity.

Bone cement is an indispensable material in orthopedic medicine. In Indonesia, the fulfillment of bone cement needs still depends on imports from other countries. Polymethyl methacrylate (PMMA) is one of the main ingredients of bone cement which can be made from suspension polymerization of methyl methacrylate monomer (MMA). Therefore, this study aims to develop a technique for producing bone cement from PMMA. The production of bone cement consists of (1) the manufacture of PMMA, (2) the mixing of solid mixtures, (3) the mixing of solid mixtures and liquid mixtures, and (4) the molding of bone cement composites. The concentrations of barium sulfate (BaSO4) used were 7%, 9%, and 11% by weight. Composite products were analyzed by Scanning Electron Microscopy (SEM), Proton Nuclear Magnetic Resonance (H-NMR), and Compressive Strength. The increase of BaSO4 can trigger more smooth surface of bone cement composite. The tacticity from H-NMR shows that the bone cement dominantly consists of syndiotactic (58.83-59.91%) molecular arrangement. The highest compressive strength was 84.2 MPa which was obtained in 9% BaSO4 weight.

INTRODUCTION:Tracheal decellularization is one of the main processes to provide tracheal substitutes for tracheal replacement. Recently, studies have been held for agents and combinations of processes for tracheal decellularization with different outcomes. This study aimed to evaluate the efficacy of tracheal decellularization by the immunogenic cellular elements using residual deoxyribonucleic acid (DNA) contents (ng/mg) and the preservation of biomechanical integrity by glycosaminoglycan (GAG) content (μg/mg), modulus tensile strength (MPa), ultimate tensile strength (MPa), and stress loading of 50% deformation (N). METHODS:We conducted a meta-analysis based on PRISMA criteria. Data from experimental studies in MEDLINE, Scopus, and ScienceDirect from inception to August 21, 2023, were sought and computed using RevMan 5.4. The outcomes of tracheal decellularization were evaluated through effect size estimates based on pooled Standardized Mean Difference (SMD) with 95% CI. RESULTS:Tracheal decellularization has significantly reduced the DNA and GAG content after the process (SMD: -11.77, 95% CI [-13.92, -8.62], p < 0.00001; SMD: -6.70, 95% CI [-9.55, -3.85], p < 0.00001). No significant outcomes were observed in modulus and ultimate tensile strength result (SMD: -0.14, 95% CI [-0.64, 0.36], p = 0.58; SMD: 0.11, 95% CI [-0.57, 0.80], p = 0.75). The stress loading of 50% deformation was observed to significantly lower (SMD: -1.61, 95% CI [-2.49, -0.72], p = 0.0004). CONCLUSION:Tracheal decellularization has been proven to effectively remove immunogenic cells. However, extracellular matrix integrity and biomechanical properties vary among different decellularization techniques, indicating a need for further refinement to achieve better preservation.

Bone cement is a material used in many orthopedic surgeries. Polymethyl Methacrylate (PMMA) is one of the acrylic-based bone cement materials. PMMA will be mixed with an activator (N, N-Dimethyl-p-toluidine (DMPT)), initiator (Benzoyl Peroxide (BPO)), radiopacifier / filler (BaSO4), and Methyl Methacrylate monomer. Once the materials were mixed, the activator react with the initiator to form radicals and activate the bulk polymerization reaction between the MMA monomer and PMMA molecules. The bulk polymerization reaction occurs exothermically and increases the bulk temperature. Barium sulfate (BaSO4) is an inorganic compound that can be acted as both radiopacifier and filler in bone cement. The specific objective of this study was to describe the effect of BaSO4 in bone cement composite formation. The solid material; PMMA, BPO, and BaSO4 were mixed firstly. The liquid portions; N, N-Dimethyl-p-toluidine (DMPT), and MMA were mixed and then poured into the solids one in a stainless-steel bowl. The bulk temperature was recorded after a one-minute mixing process. The samples were characterized by Gel Permeation Chromatography (GPC) and Differential Scanning Calorimetry (DSC). The highest setting temperature and setting time were 107.3°C and 10.6 min which was obtained in BaSO4 content variables of 7% and 11%, respectively. The average molecular weight of the samples was 561.5-1,332.0 kDa. From the DSC result, the glass temperature of the samples was 119.17-119.87°C.

Bone grafting has emerged as a key solution in bone defect management such as allograft, graft of bone from another individual. However, bone allografts usually undergo rigorous preparation to eliminate immune-triggering elements. The deep-freezing methods may delay graft use, while cryopreservation using liquid nitrogen allows rapid freezing but may alter graft characteristics. The aim of this study was to investigate the post-preservation changes in bone allograft characteristics and to compare the effectiveness of deep-freezing and liquid nitrogen methods using animal model. An experimental study using a post-test only control group design was conducted. Fresh-frozen femoral cortical bone was obtained from male New Zealand white rabbits. Preservation by deep-freezing involved placing bone samples in a -80°C freezer for 30 days. For liquid nitrogen preservation, bone grafts were immersed in liquid nitrogen for 20 min, followed by a 15-min rest at room temperature and a final immersion in 0.9% sodium chloride at 30°C for 15 min. Bone samples then underwent evaluation of cell viability, compression, and bending tests. Cell viability test employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and the compression and bending tests used the Universal Testing Machine (UTM). Independent Student t-test or Mann-Whitney U test were used to compare the methods as appropriate. Our study found that the use of deep-freezing and liquid nitrogen resulted in similar outcomes for cell viability, compression, and bending tests, with p-values of 0.302, 0.745, and 0.512, respectively. Further exploration with larger sample sizes may help to optimize the methods for specific applications.

The process of decellularization is crucial for producing a substitute for the absent tracheal segment, and the choice of agents and methods significantly influences the outcomes. This paper aims to systematically review the efficacy of diverse tracheal decellularization agents and methods using the PRISMA flowchart. Inclusion criteria encompassed experimental studies published between 2018 and 2023, written in English, and detailing outcomes related to histopathological anatomy, DNA quantification, ECM evaluation, and biomechanical characteristics. Exclusion criteria involved studies related to 3D printing, biomaterials, and partial decellularization. A comprehensive search on PubMed, NCBI, and ScienceDirect yielded 17 relevant literatures. The integration of various agents and methods has proven effective in the process of tracheal decellularization, highlighting the distinct advantages and drawbacks associated with each agent and method.

Currently, a tissue-engineered trachea has been popularly used as a biological graft for tracheal replacement in severe respiratory diseases. In the development of tissue-engineered tracheal scaffolds, in vitro studies play a crucial role in allowing researchers to evaluate the efficacy and safety of scaffold designs and fabrication techniques before progressing to in vivo or clinical trials. This research involved the decellularization of goat trachea using SDS, H2O2, and their combinations. Various quantitative and qualitative assessments were performed, including histological analysis, immunohistochemistry, and biomechanical testing. Hematoxylin and eosin staining evaluated the cellular content, while safranin O-fast green and Masson’s trichrome staining assessed glycosaminoglycan content and collagen distribution, respectively. The immunohistochemical analysis focused on detecting MHC-1 antigen presence. Tensile strength measurements were conducted to evaluate the biomechanical properties of the decellularized scaffolds. The results demonstrated that the combination of SDS and H2O2 for goat tracheal decellularization yielded scaffolds with minimal cellular remnants, low toxicity, preserved ECM, and high tensile strength and elasticity. This method holds promise for developing functional tracheal scaffolds to address severe respiratory diseases effectively.

Primary malignant bone tumors constitute a small but significant portion, accounting for 3–5% of childhood cancers. Cryosurgery, utilizing liquid nitrogen to induce tumor necrosis through extreme cold, emerges as a favorable surgical technique for bone tumor. This study delves into the clinical and radiological outcomes of individuals underwent cryosurgery. This descriptive study focused on patients with primary malignant bone tumors subjected to wide resection and cryosurgery with follow-up period from 6 up to 48 months from year 2018 - 2023. The data was collected from medical records and database, we evaluated the demographic data, clinical with Musculoskeletal Tumor Society (MSTS), radiological outcome with International Society of Limb Salvage (ISOLS) score, and the complications of cryosurgery observed. Among the 37 patients examined, 20 males and 17 females were averaging 21.7 years of age. 29 of 37 (78%) cases identified as osteosarcoma most common location in the epimetaphyseal of the long bone with Grade Enneking IIB. MSTS score averaged 25.35 ± 5.54, with more than 68% achieving excellent and good score. ISOLS for radiological score revealed 37.8% with an excellent score, 48.6% with a good score. The most common complication, reccurence, occurs in 6 cases (16.2%). Patients with primary malignant bone tumors who underwent cryosurgery showed successful clinical and radiological outcomes, as measured by MSTS and ISOLS scores. This underscores the significance of cryosurgery in primary malignant bone tumor as favorable and cost-effective treatment, showcasing improved functionality and positive radiological results.

Introduction: The Secretome consists of proteins secreted by human cells, containing various serum proteins and growth factors (GFs) that can aid in tissue repair and regeneration. The two most commonly utilized tissues for producing secretomes are Adipose-Derived Mesenchymal Stem Cells (AdMSCs) and Bone Marrow Mesenchymal Stem Cells (BM-MSCs). Hypoxic conditions are also one of the critical preconditioning factors that enhance the efficacy of the secretome. By analyzing and comparing the growth factor profiles between these two cellular sources, we aim to elucidate their potential therapeutic applications and further our understanding of the underlying mechanisms driving their regenerative abilities. Methods: A randomized controlled post-test-only group design study was conducted at the Cell and Tissue Bank of Dr. Soetomo Hospital. Secretome was derived from AdMSCs and BM-MSCs cultured under hypoxic conditions (5% O-2 level). VEGF, PDGF, IGF-1, TGF-beta, and bFGF from each group were analyzed by ELISA and compared. Results: Each group consisted of 7 samples. PDGF levels were significantly higher in the AdMSCs group (7.99 +/- 0.644) compared to the BM-MSC group (7.21 +/- 0.46); (p = 0.013; p<0.05). Meanwhile, IGF-1 levels were significantly higher in the BM-MSCs group (16.42 +/- 1,878) compared to the AdMSCs group (14.2 +/- 0.988); (p = 0.021; p<0.05). There were no significant differences in other growth factors between the two groups, including bFGF (0.57 +/- 0.05 vs. 0.61 +/- 0.07; p = 0.207), VEGF (1,644.00 +/- 123.65 vs. 1,588.26 +/- 117.80; p = 0.405), and TGF-beta (1,323.29 +/- 145.36 vs. 1,264.06 +/- 121.60; p = 0.425). Conclusion: No significant differences in VEGF, TGF- beta, and bFGF between the two groups. Therefore, AdMSC can be a better alternative to BM-MSC as it is easier to obtain, readily available, and has higher PDGF content.

Arteriovenous malformation (AVM) is a genetic vascular anomaly that can significantly affect daily activities. Its occurrence varies by race and gender, being more common in women. This report examines AVM in two siblings, aged 12 and 14. Clinical, radiological, and pathological evaluations revealed differing tumor sizes, expansions, and causes of vascular enlargement. Consequently, the siblings received different treatments: one underwent embolization, while the other had a wide excision. Both approaches resulted in favorable outcomes. AVM is a vascular neoplasm that may present at birth or be discovered later, often during routine check-ups or after trauma. The familial nature of AVM in this case emphasizes the variability in presentation and treatment response. Established diagnostic and therapeutic guidelines may not always be applicable, necessitating individualized treatment plans. This case highlights the importance of tailored treatment approaches for familial AVM, demonstrating successful outcomes with both embolization and wide excision

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

Background: Demineralized Bone Matrix (DBM) is an alternative biomaterial that needs particular acid and a specific time to optimize the growth factors preservation. The best demineralization protocol for preserving growth factors in DBM is currently unavailable. This study aimed to investigate DBM extraction methods using different acids and times to maintain the optimum growth factors.Methods: This in vitro experimental laboratory study used a randomized controlled post-test-only group design. We characterized the IGF-1, BMP2, and TGF-β content of 1 gram of New Zealand White Rabbit cortical bone immersed in 0.6 M hydrochloric and 0.5 M acetic acid at 3, 6, and 9 days. We then analyzed the differences in growth factor levels in each acid and analyzed them statistically.Results: IGF-1 levels were higher in DBM demineralized acetic acid than hydrochloric acid. BMP-2 and TGF-β levels were higher in DBM demineralized using hydrochloric acid. The concentration of growth factors decreased with time in DBM demineralized using acetic acid. The highest growth factor level was obtained after six days of immersion in hydrochloric acid.Conclusion: The average value of IGF-1 in DBM demineralized with acetic acid was higher than in hydrochloric acid. Otherwise, BMP 2 and TGF-β were better in hydrochloric acid. We also found that the growth factor level in hydrochloric acid reached its peak level at six days and then decreased. These results suggest the importance of not over-demineralizing the bone to maintain growth factors, and further research should be conducted to improve DBM processing.

Background: 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% O2 (normoxic group) and 1%, 3%, and 5% O2 (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.

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.

The effect of the secretome addition to the bovine hydroxyapatite (BHA) as a bone graft candidate was observed through some in vitro testing, histopathological anatomy test, and immunohistochemistry test. BHA and secretomes are first synthesized and then immersed in secretomes to gain the BHA-secretome composite scaffold. The scaffold was freeze-dried and underwent some in vitro and in vivo tests such as morphology, functional group, MTT assay, degradation, and swelling tests. The in vivo test was done to know the woven bone, collagen type I, and osteonectin amount formed during the implantation in rabbits for 30 and 60 days. Based on the SEM morphology test, the average pore size in the two groups of samples was 462.15 µm. All scaffolds from this study contain hydroxyapatite’s functional groups matched with literature and are non-toxic after being tested by the MTT assay. These scaffolds could be applied as bone grafts because the percentage of sample degradation is < 30

Background:The COVID-19 pandemic had greatly and negatively impacted health services including the management of bone and soft tissue sarcoma. As disease progression is time-sensitive, decision taken by the oncology orthopedic surgeon on performing surgical treatment determines the patient outcome. On the other hand, as the world tried to control the spread of COVID-19 infection, treatment re-prioritization based on urgency level had to be done which consequently affect treatment provision for sarcoma patients. Patient and clinician's concern regarding the outbreak have also inflicted on treatment decision making. A systematic review was thought to be necessary to summarize the changes seen in managing primary malignant bone and soft tissue tumors. Methods:We performed this systematic review in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. The review protocol had been registered on PROSPERO with submission number CRD42022329430. We included studies which reported primary malignant tumor diagnosis and its surgical intervention from March 11th, 2020 onwards. The main outcome is to report changes implemented by different centers around the world in managing primary malignant bone tumors surgically in response to the pandemic. Three electronic medical databases were scoured and by applying eligibility criteria. Individual authors evaluated the articles' quality and risk of bias using the Newcastle-Ottawa Quality Assessment Scale other instruments developed by JBI of the University of Adelaide. The overall quality assessment of this systematic review was self-evaluated using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Checklist. Results:There were 26 studies included in the review with various study designs, conveyed in almost all continents. The outcomes from this review are change in surgery time, change in surgery type, and change in surgery indication in patients with primary bone and soft tissue sarcoma. Surgery timing has been experiencing delay since the pandemic occurred, including delay in the multidisciplinary forum, which were all related to lockdown regulations and travel restrictions. For surgery type, limb amputation was preferred compared to limb-salvage procedures due to shorter duration and simpler reconstruction with better control of malignancy. Meanwhile, the indications for surgical management are still based on the patient's demographics and disease stages. However, some would stall surgery regardless of malignancy infiltration and fracture risks which are indication for amputation. As expected, our meta-analysis showed higher post-surgical mortality in patients with malignant bone and soft tissue sarcoma during the COVID-19 pandemic with odds ratio of 1.14. Conclusion:Surgical management of patients with primary bone and soft tissue sarcoma has seriously been affected due to adjustments to the COVID-19 pandemic. Other than institutional restrictions to contain the infection, patient and clinician's decisions to postpone treatment due to COVID-19 transmission concern were also impactful in treatment course. Delay in surgery timing has caused higher risk of worse surgical outcome during the pandemic, which is aggravated if the patient is infected by COVID-19 as well. As we transition into a post-COVID-19 pandemic period, we expect patients to be more lenient in returning for their treatment but by then disease progression might have taken place, resulting in worse overall prognosis. Limitation to this study were few assumptions made in the synthesis of numerical data and meta-analysis only for changes in surgery time outcome and lack of intervention studies included.

Introduction: 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.

Background: 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% O2), middle (3% O2), and severe hypoxia (1% O2) groups and the normoxia (21% O2) 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% O2 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.

Background: Periodontal disease is common in both developed and developing countries and affects around 20-50% of the global population, especially in adolescents, adults and the elderly is a public health problem. ADMSCs have the advantage of regenerating damaged tissue with high quality. DDM in the form of slices can improve healing in the mandibular sockets of molar teeth. The combination of ADMSC-DDM is expected to accelerate bone regeneration.Objectives: To analyze the combination of ADMSCs-DDM at increasing bone marker expression in periodontitis rats.Methods: This research is experimental with a randomized control group post-test-only design. A total of 50 male Wistar rats were divided into four groups: 1) normal group (K); 2) CP model (K + ); 3) CP model and treated with DDM scaffold therapy (K(s)); 4) CP model and treated with ADMSCs-DDM combination therapy (K(sc)). Making a CP model with injected LPS P. gingivalis into interproximal gingiva of the right first and second lower molars. The in vivo research stage was the implantation of the DDM scaffold and the ADMSCs-DDM combination in the rat periodontal pocket. Rats were euthanized on days 7, 14, and 28, and immunohistochemistry of STRO-1, RUNX-2, OSX, COL-I, and OCN was performed. DDM scaffolds are made in 10%, 50% and 100% concentrations for MTT testing. Statistical results were analyzed with Kruskal-Wallis and Mann-Whitney tests.Results: The results of the MTT scaffold DDM were significant in the 10%, 50%, and 100% dilution groups (p < 0.05). The results showed there was a substantial difference in the expression of STRO-1 between the study groups (p < 0.05). The (K(sc)) was significantly higher than the (K) in RUNX-2 expression (p < 0.05). OSX expression showed significant results between study groups (p < 0.05). The expression of OCN and COL-I showed a significant difference in all study groups on day 28, where the (K(sc)) was higher than the (K) (p < 0.05).Conclusions: Administration of the ADMSCs-DDM combination can accelerate alveolar bone regeneration on day 28. There is a mechanism of alveolar bone regeneration through the STRO-1, RUNX-2, OSX, and the COL-I pathway in periodontitis models.(c) 2023 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: Mesenchymal stem / stromal cell therapy (MSCs) is now an effective therapeutic modality for treating various diseases. In its application, stem cells require signaling molecules which can be growth factors, cytokines, or chemokines. Signal molecules work orderly and are greatly influenced by the physiological environment. Stem cell culture techniques with hypoxic conditions can produce growth factors close to physiological conditions in fractures. This study aims to perceive the different expressions of some growth factors in cultured normoxic and hypoxic BMSC.Methods: This study is an in vitro laboratory experimental study of normoxic Bone Marrow Stem Cells (BMSCs) and Hypoxic Bone Marrow Stem Cells (BMSCs) cultures. The BMSCs experimental unit was taken from rabbits and then propagated in vitro and cultured under two conditions, normoxia and hypoxia. Then the number of VEGF, TGF-β, BMP-2 growth fractures was observed using ELISA.Results: VEGF, TGF-β, and BMP-2 expressions showed significant differences between the normoxia and hypoxia groups. VEGF, TGF-β, and BMP-2 expression were higher in the hypoxia group compared with the normoxia group (p < 0.05).Conclusion: The expression analysis of TGFβ-1, VEGF, and BMP-2 growth factors in cultured BMSC were statistically significant between normoxic and hypoxic conditions. TGFβ-1, VEGF, and BMP-2 expressions increase in hypoxic conditions.