Tesis

Efektivitas Granulocyte-Colony Stimulating Factor dalam Meningkatkan Penyembuhan Fraktur pada Model Delayed Union Tikus Sprague-Dawley = Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Implantation Therapy in Patients with Lower Back Pain due to Degeneration of Intervetebral Discus.

Pendahuluan: Delayed union merupakan permasalahan yang dapat terjadi pasca penyembuhan fraktur yang secara signifikan mengganggu kualitas hidup pasien. Telah banyak penelitian yang dilakukan berdasarkan pendekatan konsep diamond untuk memecahkan masalah delayed union. Granulocyte-colony stimulating factor (G-CSF) merupakan salah satu dari berbagai zat yang diketahui mempunyai peranan positif dalam penyembuhan jaringan skeletal atau regenerasi ajuvan. Penelitian ini dilakukan untuk melihat efek pemberian G-CSF dalam mempengaruhi penyembuhan fraktur delayed union. Material dan Metode: Penelitian eksperimental dilakukan dengan randomized post test only control group design pada 24 hewan coba tikus putih Sprague-Dawley yang telah mengalami model delayed union. Penelitian membandingkan antara kelompok perlakuan yg diinjeksi subkutan G-CSF dengan kelompok kontrol dan dibagi menjadi empat kelompok (n=6). Harvest dan follow up histomorfometri dan imunohistokimia dilakukan pada dua kelompok di minggu kedua (KM2 dan PM2) dan dua kelompok lagi pada minggu keempat (KM4 dan PM4). Analisis histomorfometri terdiri dari presentase area tulang imatur, tulang rawan dan area fibrosa dengan pulasan Hematoxylin-Eosin (HE). Sedangkan evaluasi semikuantitatif imunohistokimia dengan ekspresi BMP-2 melalui skor imunoreaktif (IRS). Hasil: Pada evaluasi parameter histomorfometri dan imunohistokimia didapatkan area fibrosis secara signifikan lebih sedikit (p < 0,001) dan ekspresi BMP 2 lebih tinggi (p=0,008) pada kelompok perlakuan minggu kedua dibandingkan kontrol. Serta presentase area woven bone secara bermakna lebih besar (p=0,015), area fibrosis lebih sedikit (p=0,002) dan ekspresi BMP 2 lebih tinggi (p=0,004) pada perlakuan minggu keempat dibandingkan dengan kontrol. Kesimpulan: G-CSF terbukti meningkatkan kecepatan penyembuhan pada tikus putih Sprague-Dawley pada model delayed union dievaluasi dari aspek histomorfometri dan imunohistokimia.
Kata kunci: Granulocyte-colony stimulating factor, BMP-2, penyembuhan fraktur, delayed union, histomorfometri, imunohistokimia.


Introduction: Delayed union is a problem that can occur after fracture healing, which significantly impairs the patient's quality of life. Many studies were conducted based on the diamond concept approach to solve the problem of delayed union. Granulocyte-colony stimulating factor (G-CSF) is one of the various substances known to have a positive role in healing skeletal tissue or adjuvant regeneration. This study was conducted to see the effect of G-CSF in affecting delayed union fracture healing. Methods: . The experimental study was conducted by randomized posttest only control group design on 24 experimental animals Sprague-Dawley white rats that had experienced delayed union models. The study compared the treatment group injected with subcutaneous G-CSF with a control group and was divided into four groups (n=6). Harvest and follow-up histomorphometry and immunohistochemistry were performed in two groups in the second week (KM2 and PM2) and two more groups in the fourth week (KM4 and PM4). The histomorphometric analysis consisted of the percentage of immature bone area, cartilage, and fibrous area with Hematoxylin-Eosin (HE) streaks. Meanwhile, the semiquantitative evaluation of immunohistochemistry with the expression of BMP-2 through the immunoreactive score (IRS). Results: In the evaluation of histomorphometric and immunohistochemical parameters, there were significantly differences less fibrosis area (p = 0,001) and higher BMP 2 expression (p = 0,008) in treatment week two compared to control. In addition, there were also significantly more woven bone area (p = 0,015), less fibrosis area (p = 0,002) and higher BMP 2 expression (p = 0,004) in treatment group week four compared to control. Conclussion: G-CSF was shown to increase the speed of healing in SpragueDawley rats on delayed union models evaluated from histomorphometric and immunohistochemical aspects.
Keywords: Granulocyte-colony stimulating factor, BMP-2, fracture healing, delayed union, histomorphometry, immunohistochemistry.