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"This book that addresses the modern aspects of bone healing and repair. Recent breakthroughs in understanding the regulatory aspects of bone formation and resorption, in both research and clinical arenas offer new modalities to induce, enhances and guide repair processes in bone for the benefit of millions of patients with conditions such as nonunion fractures, critical size defects, orthodontic tooth movement, periodontal bone loss, intraosseous implants and deformed bones."

"This volume presents a new contribution for the field of Tissue Engineering with a focus on the development of mathematical and computational methods that are relevant to understand human tissues, as well to model, design, and fabricate optimized and smart scaffolds."

"Latar Belakang: Ti-6Al-4V merupakan material implan yang sering digunakan untuk aplikasi biomedis, tetapi biaya produksi yang masih mahal. Sehingga diperlukan perlakuan panas untuk mengurangi biaya produksi dengan hasil produk yang optimal. Salah satu syarat diterimanya material implan yaitu harus kompatibel dengan jaringan sekitar. Tujuan: Mengamati efek implantasi material implan Ti-6Al-4V ELI dengan perlakuan panas 850°C pada regenerasi tulang femur tikus yang diamati melalui gambaran histologi. Metode: Penelitian ini menggunakan desain studi ekperimental pada 2 tikus betina Sprague Dawley di setiap kelompok. Terdapat 3 kelompok penelitian yang mencakup kelompok kontrol normal, kelompok kontrol defek, serta kelompok perlakuan yang diberi defek dan diimplantasi bahan uji material implan Ti-6Al-4V ELI dengan perlakuan panas 850°C. Tikus dikorbankan pada minggu ke-4 lalu dilakukan pengamatan histologis menggunakan skoring histologi Salkeld yang dimodifikasi. Hasil: Hasil skor histologi pada kedua sampel kelompok kontrol defek dan sampel-1 kelompok perlakuan yaitu 2 yang menandakan proses pembentukan tulang baru mencapai tahap pembentukan fibrokartilago. Pada sampel-2 kelompok perlakuan didapatkan hasil skor histologi 3 yang menandakan proses pembentukkan tulang sudah mencapai tahap terjadinya mineralisasi kartilago. Kesimpulan: Implantasi material implan Ti-6Al-4V ELI dengan perlakuan panas 850°C dapat diterima oleh jaringan tulang disekitarnya diamati dari proses regenerasi tulang yang ditunjukkan oleh adanya fibrosa, fibrokartilago, dan kartilago yang termineralisasi. 

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Background: Ti-6Al-4V is an implant material that is often used to biomedis application but the production costs are still expensive, so that heat treatment is needed to reduce production costs with optimal product results. One of the conditions for implant material is that it must be compatible with surrounding tissue.

Objective: To evaluate the effect of Ti-6Al-4V ELI implan material implantation with 850°C heat treatment on the regeneration of rat femoral bone observed through histology.

Method: This study used an experimental study design with two female Sprague Dawley Rattus novergicus rat on each group. There were three observation groups including normal control group, defect control group, and one treatment group that was given a defect and implanted by the implant material (Ti-6Al-4V ELI) with 850° C heat treatment. Rats were sacrificed in the fourth week and performed histological observation using modified Salkeld scoring.

Result: The results obtained from histological scoring of 2 samples of control group and sample-1 of treatment group are 2 which indicate that they reached the formation stage of fibrocartilago tissue. The histological results of sample-2 treatment groups is 3 which indicates the recovery process have reached mineral cartilage mineralization.

Conclusion: Implantation of Ti-6Al-4V ELI implant material with 850°C heat treatment is acceptable within the nearest bone tissue, observed from bone regeneration process which is indicated by the presence of fibrous, fibrocartilages, and mineralized cartilages."

"Latar Belakang: Ti-6Al-4V adalah salah satu bahan implan yang paling umum digunakan. Dalam upaya mengurangi biaya produksi implan titanium, bahan dipanaskan untuk mengoptimalkan produk akhir mereka. Salah satu kondisi yang perlu dipenuhi untuk bahan implan baru adalah biokompatibilitas bahan untuk jaringan di sekitarnya. Tujuan: Untuk memahami efek implantasi material implan Ti-6Al-4V ELI yang dipanaskan pada 10500C pada tulang paha tikus Sprague Dawley melalui studi histologis. Metode: Desain penelitian eksperimental digunakan dalam penelitian ini dengan tikus Sprague Dawley betina yang dibagi menjadi tiga kelompok: kelompok perlakuan; kelompok kontrol normal; dan kelompok kontrol cacat, yang dibuat lubang pada tulang paha. Dua tikus digunakan di masing-masing kelompok. Pada kelompok yang diberi perlakuan, defek tulang paha diimplantasikan dengan material implan Ti-6Al-4V ELI yang dipanaskan 10500C. Tikus dikorbankan setelah empat minggu dan dievaluasi secara histologis menggunakan Salkeld Histological Scoring yang dimodifikasi. Hasil: Skor histologis kelompok sampel 1 yang diobati adalah 3 yang berarti regenerasi tulang yang hampir sempurna, ditunjukkan oleh penampilan tulang rawan mineral. Nilai untuk kelompok perlakuan sampel 2 dan kelompok kontrol cacat sampel 1,2 adalah 2, yang berarti regenerasi tulang hanya mencapai fase pembentukan fibrocartilage. Kesimpulan: Regenerasi tulang dapat diperoleh di sekitar lokasi implantasi 10500C yang dipanaskan Ti-6Al-4V ELI material implan yang ditunjukkan oleh adanya jaringan fibrosa, fibrocartilage, dan tulang rawan termineralisasi.

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Background: Ti-6Al-4V is one of the most commonly used implant materials. In an effort to reduce the cost of producing titanium implants, the material is heated to optimize their final product. One of the conditions that need to be met for new implant material is the biocompatibility of the material for the surrounding tissue.

Objective: To understand the effect of implantation of TiI 6Al-4V ELI material that was heated at 10500C on the femur of Sprague Dawley rats through histological studies.

Methods: The experimental research design used in this study with female Sprague Dawley mice was divided into three groups: the treatment group; normal control group; and the deformed control group, which made a hole in the femur. Two mice were used in each group. In the treated group, femur defects were implanted with the implant material 10500C EL-Ti-6Al-4V. Mice were sacrificed after four weeks and evaluated histologically using modified Salkeld Histological Scoring.

Results: The histological score of the sample group 1 treated was 3, which means almost perfect bone regeneration, indicated by the appearance of mineral cartilage. The values ​​for the sample 2 treatment group and the sample defect control group 1,2 are 2, which means bone regeneration only reaches the fibrocartilage formation phase.

Conclusion: Bone regeneration can be obtained around the implantation site of ELI Ti-6Al-4V implant material heated by 10500C which is indicated by the presence of fibrous tissue, fibrocartilage, and mineralized cartilage."

"Fraktur tulang merupakan kondisi kerusakan pada sebagian atau seluruh kontinuitas tulang yang dapat menyebabkan beberapa komplikasi seperti infeksi, pendarahan, kerusakan pada saraf dan pembuluh darah, dan defek. graphine oxide/hidroksiapatit/fibrin, functionalized graphite/hidroksiapatit/fibrin, functionalized multiwalled carbon nanotubes/hidroksiapatit/fibrin, dan hidroksiapatit/fibrin perancah HAp/F memiliki ukuran pori 0,5 – 4,1 μm, GO/HAp/F 2,6 – 6,1 μm, fG/HAp/F 0,7 – 14,1 μm dan fMWCNT/HAp/F 1,5 – 11,1 μm. Terdapat gugus PO43- , O-H, C-H, C-O alifatik, dan amida I pada setiap kelompok perancah. Dengan penambahan gugus fungsi C=O pada perancah dengan penambahan material karbon. Nilai kekuatan tekan pada perancah GO/HAp/F, fG/HAp/F, dan fMWCNT/HAp/F sesuai dengan kekuatan tekan cancellous bone. Persentase porositas paling besar padaperancah GO/HAp/F sebesar 9,99 ± 2,85%. Perancah GO/HAp/F memiliki persentase swelling yang paling tinggi dan laju degradasi yang paling lambat. Sedangkan retensi yang paling baik ditunjukkan oleh perancah fG/HAp/F dengan persentase 8,27%. Berdasarkan keseluruhan hasil, perancah HAp/F dengan penambahan material GO mempunyai karakteristik fisika-kimia yang lebih baik pada penelitian ini dibandingkan dengan perancah fMWCNT atau fG.

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A fracture is a condition when the continuity of the bone is broken causing several complications such as infection, bleeding, damage to nerves and blood vessels, and disability. In this research, the solution offered is to fabricate a scaffold with a combination of biomaterials or composites in the form of graphine oxide/hydroxyapatite/fibrin, functionalized graphite/hydroxyapatite/fibrin, functionalized multiwalled carbon nanotubes/hydroxyapatite/fibrin, and hydroxyapatite/fibrin. Scaffolds were synthesized using the freeze-drying method. This study aims to determine the physico-chemical characteristics of the four groups of scaffolds. Based on the results of SEM-EDS, the HAp/F scaffold has a pore size of 0.5 – 4.1 μm, GO/HAp/F has 2.6 – 6.1 μm, fG/HAp/F has 0.7 – 14.1 μm and fMWCNT/HAp/F has 1.5 – 11.1 μm. There were PO43- , O-H, C-H, aliphatic C-O and amide I groups in each scaffold. Additionally the C=O functional group on the scaffold with the addition of carbon material. The compressive strength values of GO/HAp/F, fG/HAp/F, and fMWCNT/HAp/F scaffolds correspond to the compressive strength of the cancellous bone. The highest percentage of porosity is GO/HAp/F scaffolds with 9.99 ± 2.85%. GO/HAp/F scaffolds had the highest swelling percentage and the slowest degradation rate. Meanwhile, the best retention was shown by fG/HAp/F scaffold with a percentage of 8.27%. Based on the overall results, the HAp/F scaffold with the addition of GO material had better physico-chemical characteristics in this study than fMWCNT or fG scaffolds."

"Fraktur tulang merupakan kondisi ketika kontinuitas dari tulang rusak sehingga menyebabkan perubahan pada bentuk tulang. Rekayasa jaringan tulang merupakan kombinasi dari perancah, sel, dan biofaktor dimana perancah merupakan komponen yang memainkan peranan penting. Solusi yang ditawarkan adalah memfabrikasi perancah dengan gabungan biomaterial atau komposit berupa graphite/ hydroxyapatite/ fibrin (G/HAp/F), graphene oxide/ hydroxyapatite/ fibrin (GO/HAp/F), multiwalled carbon nanotubes/ hydroxyapatite/ fibrin (MWCNT/HAp/F), dan hydroxyapatite/ fibrin (HAp/F) dengan penambahan material karbon (MWCNT, GO, dan G) sebanyak 1% wt, HAp sebanyak 2% wt, dan penambahan fibrin dengan perbandingan HAp:Fibrin senilai 20:1. Metode: Perancah disintesis dengan menggunakan metode freeze-drying. Parameter uji dilakukan melalui uji biokompatibilitas atau viabilitas sel (MTS assay), uji diferensiasi sel (pewarnaan alizarin red), dan analisa statistik. Pengujian tersebut dilakukan untuk melihat perbandingan antara keempat kombinasi perancah dalam menginduksi osteogenesis dan mempercepat proses regenerasi tulang. Hasil: Fabrikasi perancah dengan metode freeze-drying menghasilkan perancah dengan ukuran rata-rata diameter 0,68 cm dan tinggi 0,41 cm. Uji viablitas menunjukkan perancah dengan penambahan karbon menunjukkan viabilitas sel yang buruk, tidak menginduksi adhesi dan proliferasi sel, meskipun sel cenderung bermigrasi dan mendekati perancah. Uji diferensiasi menunjukkan perancah dengan penambahan karbon gagal dalam menginduksi diferensiasi sel osteogenik, Sel yang berdiferensiasi hanya ditemukan pada perancah HAp/F.

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A fracture is a condition when the continuity of the bone is broken, causing a change in the shape of the bone. Bone tissue engineering is a combination of scaffolds, cells, and biofactors where the scaffold is a component that plays an important role. In this study, scaffolds with a combination of biomaterials or composites in the form of graphite/ hydroxyapatite/ fibrin (G/HAp/F), graphene oxide/ hydroxyapatite/ fibrin (GO/HAp/F), multiwalled carbon nanotubes/ hydroxyapatite/ fibrin (MWCNT/ HAp/F), and hydroxyapatite/ fibrin (HAp/F) with the addition of carbon material (MWCNT, GO, and G) as much as 1% wt, HAp as much as 2% wt, and the addition of fibrin with a HAp:Fibrin ratio of 20:1 were fabricated. Scaffolds were synthesized using the freeze-drying method. The test parameters were carried out through biocompatibility or cell viability test (MTS assay) and cell differentiation test (alizarin red staining), and statistical analysis. The test was conducted to see the comparison between the three combinations of scaffolds in inducing osteogenesis and accelerating the process of bone regeneration. The scaffold fabrication using the freeze-drying method resulted in a scaffold with an average diameter of 0.68 cm and an average height of 0.41 cm. Viability test showed that the scaffolds with the addition of carbon showed poor cell viability, did not induce cell adhesion and proliferation, although cells tended to migrate and approach the scaffold. Differentiation test showed that the scaffolds with addition of carbon failed to induce osteogenic cell differentiation. Differentiated cells were only found in the HAp/F scaffold."

"Defek tulang yang kritis menimbulkan beban kesehatan yang besar secara global. Studi ini berfokus pada implantasi ADMSCs-EVs (eksosom) terhadap tikus model defek tulang kritis. Penelitian dilakukan untuk menginvestigasi kandungan miRNA pada ADMSCs-EVs (eksosom) yang memengaruhi histologi tulang defek kritis, ekspresi BMP2, dan jalur pensinyalan Wnt. Pada penelitian, dilakukan ekstraksi total RNA dan analisis Microarray terhadap miRNA. Eksperimen secara in vivo dilakukan terhadap 16 tikus SD model defek tulang kritis (8 untuk ADMSCs-EVs/eksosom, 8 untuk NaCl) serta 4 tikus SD sehat sebagai kontrol. Tikus dari masing-masing kelompok diterminasi pada hari ke-14 atau 28. Sampel defek tulang dikumpulkan untuk analisis histologi, protein, dan molekuler. Analisis histologi menunjukkan peningkatan pembentukan kalus lunak pada kelompok perlakuan ADMCs-EVs (eksosom) pada hari ke-14 atau 28 dibandingkan dengan kontrol negatif. Penurunan regulasi miR-433-3p, miR-542-3p, dan miR-328-3p pada ADMCSs-EVs (eksosom) diketahui meningkatkan ekspresi Wnt3A. Sementara itu, peningkatan ekspresi miR-93-5p pada ADMSCs-EVs (eksosom) diketahui menghambat persinyalan BMP2 yang dikonfirmasi oleh ELISA BMP2 dan ekspresi chordin (antagonis BMP-2) yang lebih tinggi. Spp1 sebagai gen hilir pensinyalan BMP-2 dan Wnt tidak menunjukkan ekspresi yang berbeda. Mikro RNA spesifik pada ADMSCs-EVs (eksosom) mengatur pensinyalan BMP-2 dan Wnt untuk meningkatkan pembentukan kalus lunak pada defek tulang kritis kelompok yang diberi perlakuan ADMSC’s EVs dibandingkan dengan kontrol negatif.

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Critical bone defects pose a substantial healthcare burden globally. This study focuses on the implantation of ADMSCs-EVs (exosomes) in critical-sized bone defect rats. This study aimed to investigate the miRNA content ADMSCs-EVs(exosomes) which affected critical-sized bone histology, BMP2, and Wnt signaling pathway. Total RNA extraction and Microarray analysis of miRNA were conducted. In vivo experiments on 16 critical-sized bone defect SD rats model (8 for ADMSCs-EVs/exosomes,8 for NaCl) in addition to four healthy control SD rats. The rats from each group were sacrificed on day 14 or 28. Bone defect samples were collected for histology, protein, and molecular analysis. Histology analysis revealed increasing soft callus formation in the ADMSC’s EVs (exosomes) treated group at days 14 or 28 in comparison to the negative control. Downregulation of miR-433-3p, miR-542-3p, and miR-328-3p in ADMSC’s EVs (exosomes) enhances Wnt3A expression. Upregulation of miR-93-5p in ADMSCs-EVs (exosomes) inhibits BMP2 signaling which is confirmed by BMP2 ELISA and higher chordin (BMP-2 antagonist) expression. Spp1 as a downstream gene of BMP-2 and Wnt signaling are indifferent. Specific miRNA inside ADMSC’s EVs (exosomes) regulates BMP-2 and Wnt signaling to enhance soft callus formation in critical size bone defect in ADMSC’s EVs treated group than in negative control."

"Bone metastases continue to be a major cause of morbidity in cancer patients, but improved understanding of the biology of bone metastases has led to the identification of drugs that are of potential value in not only their treatment but also their prevention. This book, written by recognized experts in the field, provides a detailed overview of current knowledge on this subject. One important focus of the book is the efficacy of bisphosphonates in preventing bone metastases in patients with breast, lung, and prostate cancer and disease progression in cases of multiple myeloma. The combined use of bisphosphonates and cytostatics is also discussed, with a report on first clinical data. Further topics addressed include the significance of the bone microenvironment, special issues in the elderly patient, the use of bone turnover markers, and initial findings obtained with denosumab."

"Indonesian Journal of Dentistry 2006; Edisi Khusus KPPIKG XIV: 37-41Periodontal treatment by conventional way will result in healing repair, which easily cause recurrence. Modification of treatment should be done to get an effective result, that is the regeneration of alveolar bone and to reduce inflammation. The objective of this study is to determine the alveolar bone regeneration after using DFDBA (Demineralize Freeze Dried Allograft). Quasi experimental designs with pre and post test method was used in this study, From 13 patients, 26 defects got conventional or regenerative treatment. The indicator of alveolar bone regeneration in bone height in radiographic appearence and level of osteocalsin in gingival crevicular fluid (GCF) were checked before and after the treatment, then the changes that occure were analyzed. The result of the research showed that alveolar bone regeneration only occurred to the group of regenerative treatment by using DFDBA. The conclusion is the effective periodontal tissue regeneration occurred at regenerative treatment by using DFDBA, and the osteocalsin in GCF can be used as indicator of bone growth."