The effect of a bioactive collagen membrane releasing PDGF or GDF-5 on bone regeneration

• Published in: Biomaterials 2014-03, Vol.35 (8), p.2446-2453
• Main Authors: Yamano, Seiichi, Haku, Ken, Yamanaka, Takuto, Dai, Jisen, Takayama, Tadahiro, Shohara, Ryutaro, Tachi, Keita, Ishioka, Mika, Hanatani, Shigeru, Karunagaran, Sanjay, Wada, Keisuke, Moursi, Amr M
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Advanced Basic Science; Alkaline Phosphatase - metabolism; Animals; Bone Regeneration - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Collagen - metabolism; Dentistry; Gene Expression; Growth Differentiation Factor 5 - pharmacology; Mice; Osteocalcin - genetics; Osteocalcin - metabolism; Osteogenesis; Platelet-Derived Growth Factor - pharmacology; Rats; Transcription Factors
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.12.006

Abstract Regenerative procedures using barrier membrane technology are presently well established in periodontal/endodontic surgery. The objective of this study was to compare the subsequent effects of the released platelet-derived growth factor (PDGF) and growth/differentiation factor 5 (GDF-5) from collagen membranes (CMs) on bone regeneration in vitro and in vivo. In vitro studies were conducted using MC3T3-E1 mouse preosteoblasts cultured with or without factors. Cell viability, cell proliferation, alkaline phosphatase (ALP) activity and bone marker gene expression were then measured. In vivo studies were conducted by placing CMs with low or high dose PDGF or GDF-5 in rat mandibular defects. At 4 weeks after surgery new bone formation was measured using μCT and histological analysis. The results of in vitro studies showed that CM/GDF-5 significantly increased ALP and cell proliferation activities without cytotoxicity in MC3T3-E1 cells when compared to CM/PDGF or CM alone. Gene expression analysis revealed that Runx2 and Osteocalcin were significantly increased in CM/GDF-5 compared to CM/PDGF or control. Quantitative and qualitative μCT and histological analysis for new bone formation revealed that although CM/PDGF significantly enhanced bone regeneration compared to CM alone or control, CM/GDF-5 significantly accelerated bone regeneration to an even greater extent than CM/PDGF. The results also showed that GDF-5 induced new bone formation in a dose-dependent manner. These results suggest that this strategy, using a CM carrying GDF-5, might lead to an improvement in the current clinical treatment of bone defects for periodontal and implant therapy.