The Effects of Short‐Term Application of a Combination of Platelet‐Derived and Insulin‐Like Growth Factors on Periodontal Wound Healing

Abstract

Polypeptide growth factors are a class of potent natural biologic mediators which regulate many of the activities of wound healing including cell proliferation, migration, and metabolism. Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) have been shown to regulate DNA and protein synthesis in bone cells in vitro and to interact synergistically to enhance soft tissue wound healing in vivo. We have hypothesized that the combination of PDGF and IGF-I may, therefore, enhance regeneration of both the soft and hard tissue components of the periodontium. To test this hypothesis we performed conventional periodontal surgery on all 4 quadrants of the mouth of 13 beagle dogs with naturally occurring periodontal disease. Following flap reflection, degranulation, and root planing, all premolar teeth in 2 quadrants of each dog received a combination of 3 micrograms of recombinant PDGF-B and IGF-I in a methylcellulose gel, while the premolar teeth in the contralateral quadrants received the gel alone. Teeth in 4 additional animals also received 125I-PDGF or 125I-IGF-I in the treated sites. The clearance rate of the 125I-labeled protein, changes in local bone metabolism, and amount of new bone and cementum with inserting collagen fibers were measured. The clearance studies revealed that the half-life of the factors at the site of application was 3.0 hours for IGF-I and to 4.2 hours for PDGF-B. Greater than 96% of the radio-labeled proteins was cleared by 96 hours and no radioactivity was detected 2 weeks after application. There was a significant (P less than 0.01) 2-fold increase in uptake of the bone-seeking radiopharmaceutical Technetium 99-MDP at 2 and 4 weeks in growth factor treated sites compared to controls, indicating that there was increased metabolic activity within the bone at these sites. Computer-aided histologic analyses of biopsies obtained at 2 and 5 weeks post-operatively revealed a significant (P less than 0.01), 5 to 10 fold increase in new bone and cementum in PDGF-B/IGF-I treated sites at both time points compared to controls receiving the placebo gel. The height and total area of new bone continued to increase from 2 to 5 weeks. The new bone underwent a normal maturation process as judged by histologic appearance. A physiologic periodontal ligament space was also formed between the new bone and new cementum. There was no increase in ankylosis in the treated sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of β tricalcium phosphate particle size on recombinant human platelet-derived growth factor-BB-induced regeneration of periodontal tissue in dog

“…The use of PDGF-BB in water-soluble carriers such as methylcellulose gels for bone regenerative therapy has several limitations, the greatest of which is the rapid clearance observed in vivo, which results in an inability to maintain a therapeutic concentration over time. Lynch et al 22) noted that the half-life of topically applied PDGF-BB at the wound site was −4 hours, and that >96% had cleared within 96 hours. Taking this into consideration, in an in vitro study, Bateman et al 23) investigated whether a β-TCP scaffold could deliver a consistent dose of PDGF-BB over time.…”

“…This suggests that PDGF-BB increased residual periodontal ligament cells, which 21) , who evaluated the effect of PDGF-BB in postoperative periodontal tissue wound healing and reported that it promoted PDL fibroblast proliferation in expanded polytetrafluoroethylene membrane-protected fenestration defects in dogs. This suggests that PDGF-BB plays a critical role in mitosis and modulation of proliferation of periodontal ligament cells, thus facilitating the wound healing process and inducing formation of new cementum and bone 22) . Histological observation of samples from the experimental groups revealed that the bone and cementum areas gradually increased in size between Table 3 Percentage of mean new bone area at 2 to 8 weeks 2-8 weeks after grafting, and that this increase was clearly greater in both the L-TCP(O)-and S-TCP(G)-particle groups.…”

Growth factor delivery for oral and periodontal tissue engineering

“…PDGF-BB is the most effective on PDL cell mitogenesis and matrix biosynthesis [75,76]. Several preclinical studies were performed using the combination of PDGF-BB and IGF-I for periodontal and peri-implant bone regeneration [77][78][79][80][81][82], culminating in the first study in humans using growth factors for periodontal regeneration [83]. In a human Phase I/II clinical trial, PDGF/IGF-I were considered safe when applied topically to periodontal osseous lesions, resulting in a significant improvement in bone growth and fill of periodontal defects, compared with standard therapy [83].…”

Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB

“…In vivo study also showed that PDGF-BB enhances periodontal regeneration in beagle dogs [9] and non-human primates [10] as well as bone defect fill in a human clinical trial [11,12]. Due to its capability in promoting wound healing [13] through enhancing the formation of granulation tissues, recombinant human PDGF-BB has been approved by US Food and Drug Administration (FDA) for use in diabetic foot ulcers [14].…”