Pada penelitian ini, data yang diperoleh dianalisis secara statistik menggunakan program Statistical Product and Service Solutions (SPSS) for Microsoft Windows release 25.0. Jumlah sampel penelitian kurang dari 50
36 sampel maka digunakan uji distribusi Shapiro-Wilk untuk menentukan distribusi data. Uji statistik yang digunakan uji independent T-Test untuk membandingkan atau komparasi 2 kelompok sampel tidak berpasangan berdistribusi normal. (Dahlan, 2011).
37 H. Alur Penelitian
Bagan 2. Alur Penelitian
Kelompok P1 dan P3 diterminasi dan dilakukan pengambilan roentgen femur AP pada hari ke 14, pada area fraktur dilakukan pengambilan sampel untuk penilaian gambaran histopatologis.
Kelompok P2 dan P4 diterminasi dan dilakukan pengambilan roentgen femur AP pada hari ke 28, pada area fraktur dilakukan pengambilan sampel untuk penilaian gambaran histopatologis
Hasil penilaian radiologis dan histopatologis dianalisis dengan uji statistik Populasi Tikus Wistar Rats
Sampel 16 tikus, umur 12-14 minggu, BB 450 - 600 gram Adaptasi 1 minggu
Dibagi secara acak menjadi 4 kelompok
P3 4 tikus P2 4 tikus
Pembuatan Fraktur Femur
Fraktur kemudian difiksasi dengan menggunakan k-wire 0,8
Kelompok P1dan P2 tidak diberikan
apa-apa
Kelompok P3 dan P4 diberikan platelet rich
fibrin
P1 4 tikus P4 4 tikus
38 DAFTAR PUSTAKA
Anderson LD, Hutchins WC, Wright PE, Disney JM. Fractures of the tibia and fibula treated by casts and transfixing pins. Clin Orthop Relat Res. 1974 Nov-Dec;(105):179-91
Apley, A. G. and Solomon, L. (2017) Apley’s System of Orthopaedics and Fractures. CRC Press.1-70.
Bai M-Y, Wang C-W, Wang J-Y, Lin M-F, Chan WP. Three-dimensional structure and cytokine distribution of platelet-rich fibrin. Clinics. 2017;72:116–24.
Bais MV, Wigner N, Young M, et al. BMP2 is essential for postnatal osteogenesis but not for recruitment of osteogenic stem cells. Bone. 2009; 45(2):254–66. [PubMed: 19398045]
Bahney, C. S., Zondervan, R. L., Allison, P., Theologis, A., Ashley, J. W., Ahn, J., Miclau, T., et al. (2019) ‘Cellular biology of fracture healing’, Journal of Orthopaedic Research, 37(1), pp. 35–50. doi: 10.1002/jor.24170.
Balga R, Wetterwald A, Portenier J, et al. Tumor necrosis factor-alpha: alternative role as an inhibitor of osteoclast formation in vitro. Bone. 2006; 39(2):325–35. [PubMed: 16580896]
Bassett, CAL. Biophysical principles affecting bone structure. In: Bourne, GH., editor.
Biochemistry and Physiology of bone. 2. Academic Press; New York: 1971. p. 341-376.
Bhandari M, Guyatt GH, Swiontkowski MF, et al. Surgeons’ preferences for the operative treatment of fractures of the tibial shaft. An international survey. J Bone Joint Surg Am.
2001;83-A(11):1746–1752.
Bölükbaşi, N. et al. (2013) ‘The Use of Platelet rich fibrin in Combination With Biphasic Calcium Phosphate in the Treatment of Bone Defects: A Histologic and Histomorphometric Study’, Current Therapeutic Research - Clinical and Experimental, 75. 15–21.
Bölükbaşi, N. et al. (2013) ‘The Use of Platelet rich fibrin in Combination With Biphasic Calcium Phosphate in the Treatment of Bone Defects: A Histologic and Histomorphometric Study’, Current Therapeutic Research - Clinical and Experimental, 75. 15–21.
Bosse MJ, MacKenzie EJ, Kellam JF, et al. An analysis of outcomes of reconstruction or amputation after leg-threatening injuries. N Engl J Med. 2002; 347(24):1924–1931.
Breur GJ, VanEnkevort BA, Farnum CE, et al. Linear relationship between the volume of hypertrophic chondrocytes and the rate of longitudinal bone growth in growth plates.
Journal of Orthopaedic Research. 1991; 9(3):348–59. [PubMed: 2010838]
39 Bucholz RW, Heckman JD, Court-Brown CM. Rockwood & Green's Fractures in Adults, 6th
Edition. USA: Maryland Composition. 2006. p80-331
Carano RA, Filvaroff EH. Angiogenesis and bone repair. Drug Discovery Today. 2003;
8(21):980–9. [PubMed: 14643161]
Charan, Jaykaran, and Tamoghna Biswas. “How to calculate sample size for different study designs in medical research?.” Indian journal of psychological medicine vol. 35,2 (2013):
121-6. doi:10.4103/0253-7176.116232
Cho HH, Kyoung KM, Seo MJ, et al. Overexpression of CXCR4 increases migration and proliferation of human adipose tissue stromal cells. Stem Cells & Development. 2006;
15(6):853– 64. [PubMed: 17253948]
Choukroun J, Diss A, Simonpieri A, Girard M-O, Schoeffler C, Dohan SL, et al. Platelet rich fibrin (PRF): a second-generation platelet concentrate. Part IV: clinical effects on tissue healing. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology.
2006;101(3):e56–60.
Colnot, C. (2009) ‘Skeletal cell fate decisions within periosteum and bone marrow during bone regeneration’, Journal of Bone and Mineral Research, 24(2). 274–282.
Cooper, K. L. et al. (2013) ‘Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions’, Nature, 495(7441). 375–378.
Daley, J. M. et al. (2010) ‘The phenotype of murine wound macrophages’, Journal of Leukocyte Biology, 87(1). 59–67.
Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJJ, Mouhyi J, et al. Platelet rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology.
2006;101(3):e37–44.
Dülgeroglu TC, Metineren H. Evaluation of the effect of platelet rich fibrin on long bone healing:
an experimental rat model. Orthopedics. 2017;40(3):e479–84.
Dy, P. et al. (2012) ‘Sox9 Directs Hypertrophic Maturation and Blocks Osteoblast Differentiation of Growth Plate Chondrocytes’, Developmental Cell, 22(3). 597–609.
Einhorn TA. The cell and molecular biology of fracture healing. Clinical Orthopaedics & Related Research. 1998; 355(Suppl):S7–21. [PubMed: 9917622]
40 Einhorn, T. A. & Gerstenfeld, L. C. (2015) ‘Fracture healing: Mechanisms and interventions’,
Nature Reviews Rheumatology. Nature Publishing Group, pp. 45–54. doi:
10.1038/nrrheum.2014.164.
Fukui N, Ueno T, Ito Y, Takahashi Y, Kimura Y, Nakajima Y, et al. Quantification of growth factors in platelet-rich Fibrin: A preliminary study. J Hard Tissue Biol. 2015;24(3):231–4.
Gerstenfeld LC, Alkhiary YM, Krall EA, et al. Three-dimensional reconstruction of fracture callus morphogenesis. Journal of Histochemistry & Cytochemistry. 2006; 54(11):1215–28.
[PubMed: 16864894]
Gerstenfeld LC, Cullinane DM, Barnes GL, et al. Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. Journal of Cellular Biochemistry. 2003; 88(5):873–84. [PubMed: 12616527]
Giangregorio L, El-Kotob R. Exercise, muscle, and the applied load-bone strength balance.
Osteoporos Int. 2017;28(1):21–33.
Giannoudis PV, Papakostidis C, Kouvidis G, et al. The role of plating in the operative treatment of severe open tibial fractures: a systematic review. Int Orthop. 2009;33(1): 19–26.
Goh JC, Mech AM, Lee EH, Ang EJ, Bayon P, Pho RW. Biomechanical study on the load-bearing characteristics of the fibula and the effects of fibular resection. Clin Orthop Relat Res. 1992 Jun;(279):223-8.
Goldberg VM, Powell A, Shaffer JW, Zika J, Bos GD, Heiple KG. Bone grafting: role of histocompatibility in transplantation. J Orthop Res. 1985; 3(4):389-404.
Gordon, S. and Martinez, F. O. (2010) ‘Alternative activation of macrophages: Mechanism and functions’, Immunity. Immunity. 593–604.
Gosman JH, Hubbell ZR, Shaw CN, Ryan TM. Development of cortical bone geometry in the human femoral and tibial diaphysis. Anat Rec (Hoboken). 2013 May;296(5):774-87.
Granero-Molto F, Weis JA, Miga MI, et al. Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells. 2009; 27(8):1887–98. [PubMed: 19544445]
Hattori, T. et al. (2010) ‘SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification’, Development, 137(6). 901–911.
He L, Lin Y, Hu X, Zhang Y, Wu H. A comparative study of platelet rich fibrin (PRF) and platelet-rich plasma (PRP) on the effect of proliferation and differentiation of rat osteoblasts in
41 vitro. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology. 2009;108(5):707–
13.
He, L. et al. (2009) ‘A comparative study of platelet rich fibrin (PRF) and platelet-rich plasma (PRP) on the effect of proliferation and differentiation of rat osteoblasts in vitro’, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology, 108(5).
707–13.
Hu, D. P. et al. (2017) ‘Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes’, Development (Cambridge), 144(2). 221–234.
Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res. 1991; 9(3):383-390.
Hutson JJ Jr, et al. The treatment of gustilo grade IIIB tibia fractures with application of antibiotic spacer, flap and sequential distraction osteogenesis. Ann Plast Surg. 2010;64(5):541–552.
Ikegami, D. et al. (2011) ‘Sox9 sustains chondrocyte survival and hypertrophy in part through Pik3ca-Akt pathways’, Development, 138(8). 1507–1519.
Isern, J. et al. (2014) ‘The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function’, eLife, 3. 3696.
Joseph V, R., Sam, G. and Amol, N. V. (2014) ‘Clinical evaluation of autologous platelet rich fibrin in horizontal alveolar bony defects.’, Journal of clinical and diagnostic research : JCDR, 8(11). ZC43-7.
Karayürek F, Kadiroğlu ET, Nergiz Y, Akçay NC, Tunik S, Kanay BE, et al. Combining platelet rich fibrin with different bone graft materials: An experimental study on the histopathological and immunohistochemical aspects of bone healing. J Cranio-Maxillofacial Surg. 2019;47(5):815–25.
Kazley J, Jahangir A. Tibia Diaphyseal Fracture. [Updated 2021 Aug 14]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK537173/
Keeling JJ, Gwinn DE, Tintle SM, et al. Short-term outcomes of severe open wartime tibial fractures treated with ring external fixation. J Bone Joint Surg Am. 2008;90(12):2643–
2651.
42 Ketenjian AY, Arsenis C. Morphological and biochemical studies during differentiation and
calcification of fracture callus cartilage. Clinical Orthopaedics & Related Research. 1975;
107:266–73. [PubMed: 48443]
Kim, T. H. et al. (2014) ‘Comparison of platelet-rich plasma (PRP), platelet rich fibrin (PRF), and concentrated growth factor (CGF) in rabbit-skull defect healing’, Archives of Oral Biology, 59(5). 550–558.
Kim, P. H. & Leopold, S. S. (2012) ‘Gustilo-Anderson classification’, Clinical Orthopaedics and Related Research. Springer New York LLC, pp. 3270–3274. doi: 10.1007/s11999-012-2376-6.
Kitaori T, Ito H, Schwarz EM, et al. Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. Arthritis & Rheumatism. 2009; 60(3):813–23. [PubMed: 19248097]
Kon T, Cho TJ, Aizawa T, et al. Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. Journal of Bone & Mineral Research. 2001; 16(6):1004–14. [PubMed: 11393777]
Kumar, K. R. et al. (2016) ‘Role of plasma-rich fibrin in oral surgery’, Journal of Pharmacy and Bioallied Sciences, 8(Suppl 1). S36–S38.
Larsen P, Elsoe R, Hansen SH, Graven-Nielsen T, Laessoe U, Rasmussen S. Incidence and epidemiology of tibial shaft fractures. Injury. 2015;46(4):746–50.
Leow JM, Clement ND, Tawonsawatruk T, Simpson CJ, Simpson AH. The radiographic union scale in tibial (RUST) fractures: Reliability of the outcome measure at an independent centre. Bone Joint Res. 2016;5(4):116-121. doi:10.1302/2046-3758.54.2000628
Leung, V. Y. L. et al. (2011) ‘SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression’, PLoS Genetics, 7(11).
Lu, L. Y. et al. (2017) ‘Pro-inflammatory M1 macrophages promote Osteogenesis by mesenchymal stem cells via the COX-2-prostaglandin E2 pathway’, Journal of Orthopaedic Research, 35(11). 2378–2385.
Ma J, Ge J, Zhang S, et al. Time course of myocardial stromal cell-derived factor 1 expression and beneficial effects of intravenously administered bone marrow stem cells in rats with
43 experimental myocardial infarction. Basic Research in Cardiology. 2005; 100(3):217–23.
[PubMed: 15754085]
Maes, C. et al. (2010) ‘Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels’, Developmental Cell, 19(2). 329–
344.
Malhotra, A. et al. (2013) ‘Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes’, Archives of Orthopaedic and Trauma Surgery, 133(2). 153–165.
Marsell R, Einhorn TA. The biology of fracture healing. Injury. 2011;42(6):551–5.
Matsubara, H. et al. (2012) ‘Vascular tissues are a primary source of BMP2 expression during bone formation induced by distraction osteogenesis’, Bone, 51(1). 168–180.
Nandi, S. K. et al. (2010) ‘Orthopaedic applications of bone graft & graft substitutes: A review’, Indian Journal of Medical Research, 132(7). 15–30.
Paulsen F, Böckers TM, Waschke J, Winkler S, Dalkowski K, Mair J, et al. Sobotta anatomy textbook: English edition with Latin nomenclature. Elsevier Health Sciences; 2018.
Reichert IL, McCarthy ID, Hughes SPF. The acute vascular response to intramedullary reaming.
Microsphere estimation of blood flow in the intact ovine tibia. J Bone Joint Surg(Br).
1995;77-B:490–493.
Riskesdas (2013) Riset Kesehatan Dasar. Departemen Kesehatan Indonesia.
Rockwood, C. A., Green, D. P., & Bucholz, R. W. (2015). Rockwood and Green's fractures in adults (8th ed.). Philadelphia: Lippincott Williams & Wilkins.
Sarmiento A, Gersten LM, Sobol PA, Shankwiler JA, Vangsness CT. Tibial shaft fractures treated with functional braces. Experience with 780 fractures. J Bone Joint Surg Br. 1989 Aug;71(4):602-9.
Simpson, A. H. R. W. & Tsang, S. T. J. (2018) ‘Non-union after plate fixation’, Injury. Elsevier Ltd, 49, pp. S78–S82. doi: 10.1016/S0020-1383(18)30309-7.
Singh, A., Kohli, M. and Gupta, N. (2012) ‘Platelet Rich Fibrin: A Novel Approach for Osseous Regeneration’, Journal of Maxillofacial and Oral Surgery, 11(4). 430–434.
Singh, A., Kohli, M. and Gupta, N. (2012) ‘Platelet Rich Fibrin: A Novel Approach for Osseous Regeneration’, Journal of Maxillofacial and Oral Surgery, 11(4). 430–434.
44 Strachan RK, McCarthy I, Fleming R, et al. The role of the tibial nutrient artery. Microsphere
estimation of blood flow in the osteotomized canine tibia. J Bone Joint Surg (Br). 1990;72-B:391–394.
Thompson JH, Koutsogiannis P, Jahangir A. Tibia Fractures Overview. [Updated 2021 Aug 7].
In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513267/
Trafton PG. Closed unstable fractures of the tibia. Clin Orthop Relat Res. 1988 May;(230):58-67.
Wendeberg, B. Acta Orthopaedica. 1961. Mineral metabolism of fractures of the tibia in manstudied with external counting of Sr85; p. 1-79.
Whelan DB, Bhandari M, McKee MD, et al. Interobserver and intraobserver variation in the assessment of the healing of tibial fractures after intramedullary fixation. J Bone Joint Surg [Br] 2002;84-B:15-18.
Yang, L. et al. (2014) ‘Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation’, Proceedings of the National Academy of Sciences of the United States of America, 111(33). 12097–12102.
Zhang N, Wu Y-P, Qian S-J, Teng C, Chen S, Li H. Research progress in the mechanism of effect of PRP in bone deficiency healing. Sci world J. 2013;2013.
Zhou, X. et al. (2014) ‘Chondrocytes Transdifferentiate into Osteoblasts in Endochondral Bone during Development, Postnatal Growth and Fracture Healing in Mice’, PLoS Genetics, 10(12).