A Phase I/II Clinical Trial to Evaluate a Combination of Recombinant Human Platelet‐Derived Growth Factor‐BB and Recombinant Human Insulin‐Like Growth Factor‐I in Patients with Periodontal Disease

Abstract

The primary objective of this study was to assess the safety of recombinant human (rh) platelet-derived growth factor-BB (PDGF-BB) and (rh) insulin-like growth factor-I (IGF-I) when applied to periodontal osseous defects in humans; a secondary objective was to begin to accrue data on the therapeutic dose of these growth factors (GFs) required to stimulate periodontal regeneration. Thirty-eight human subjects possessing bilateral osseous periodontal lesions were assigned to one of two treatment groups in a split-mouth design. Following full-thickness flap reflection, test sites received local application of the therapeutic drug delivered in coded syringes by a "masked" investigator. Two dose levels were tested, 50 micrograms/ml each of rhPDGF-BB and rhIGF-I in a gel vehicle (LD-PDGF/IGF-I) and 150 micrograms/ml each of rhPDGF-BB and rhIGF-I plus vehicle (HD-PDGF/IGF-I). Control treatment consisted of either conventional periodontal flap surgery or surgery plus vehicle. Safety analyses included physical examination, hematology, serum chemistry, urinalysis, antibody titers, and radiographic evaluation of bony changes. The primary therapeutic assessment was bone fill measured at re-entry 6 to 9 months after treatment. No local or systemic safety issues were found as a result of GF administration. No patients developed antibodies to the rhGF proteins. In subjects treated with LD-PDGF/IGF-I, there were no enhancements in periodontal regeneration compared to controls. However, in patients treated with HD-PDGF/IGF-I, statistically significant increases in alveolar bone formation were noted as measured by surgical re-entry 9 months following drug delivery (P < 0.05). This corresponded to an increase of 2.08 mm of new vertical bone height and 42.3% osseous defect fill in the HD-PDGF/IGF-I subjects versus only 0.75 mm and 18.5% gains in new bone height and osseous fill, respectively, in the controls. Furcation lesions, although limited in number, responded most favorably to treatment, with 2.8 mm horizontal osseous fill. The results from this study suggest that the local application of rhPDGF-BB and rhIGF-I to periodontal lesions is safe at the dose levels studied. LD-PDGF/IGF-I did not elicit increased defect fill compared to the control; however, HD-PDGF/IGF-I resulted in a significant promotion in bone regeneration. Additional studies are warranted to more fully characterize the effects of PDGF/IGF-I on periodontal regeneration in humans.

Growth factor delivery for oral and periodontal tissue engineering

“…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]. The evaluation of PDGF alone was demonstrated in two preclinical studies in dogs.…”

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].…”

Platelet-rich Plasma: Harvesting with a Single-spin Centrifuge

“…[1][2][3][4][5] The shortand long-term effects of speeding up and enhancing grafted bone healing are under study and show a lot of promise. However, one of the drawbacks of instituting the use of plateletrich plasma (PRP) in a private general dentistry office is the initial cost of the commercially-available automated double-spin centrifuge and the necessary disposable component parts that are required for each patient.…”