Functional Assessment of Platelet-Derived Growth Factor Gene Delivery on Accelerating Oral Implant Osseointegration. Accelerating Oral Implant Osseointegration.

Abstract

The main purpose of dental implants is to restore the function of the dentition. Despite utilizing structural analyses to investigate treatment outcomes, the therapeutic effect is sometimes unclear due to a lack of direct relevance to the biomechanical function of the peri-implant tissue. While the effective function of tissue depends on the growth pattern, maturation, and load bearing situation of the apparatus, in this dissertation I homogenized the peri-implant tissue parameters under simulated loading situations to generate functional bone apparent modulus (FBAM) and functional composite tissue apparent modulus (FCAM) through the finite element (FE) optimization process. Both FBAM and FCAM were correlated to the structural parameters, and FCAM was determined to be more relevant to interfacial biomechanical characteristics with a pre-existing extraction defect, whereas FBAM within a 200 m peri-implant concentric layer was more relevant to the implant osteotomy defect.

Platelet-derived growth factor (PDGF) has been utilized for periodontal tissue regeneration based on its effects on chemotaxis and mitogenesis, which are also key events which occur during early osseointegration. However, the bioactivity of recombinant growth factor application may be significantly reduced due to its rapid degradation and diffusion in vivo. To ensure the efficiency of PDGF expression, we delivered PDGF to peri-implant osseous defects using adenovirus gene therapy vectors (AdPDGF-B) and evaluated the treatment outcome histologically, radiographically, and functionally. The results demonstrate that AdPDGF-B significantly accelerates defect fill and promotes early bone-implant contact (BIC) in a dose-dependent manner. AdPDGF-B also facilitated favorable functional implant support in the early stages of osseointegration.

There also exist some considerations regarding the potential of adenovirus-mediated gene therapy to induce virus-related pathologic changes. Thus, the local and systemic safety profile of AdPDGF-B was thoroughly examined in this dissertation in order to alleviate concerns about future gene therapy applications for clinical use. AdPDGF-B was eliminated within two weeks without significant dissemination in vivo, and no histopathologic changes or alterations of systemic parameters were noted. Taken together, this dissertation contributes a novel methodology to functionally evaluate the dynamics of osseointegration and demonstrates the feasibility of AdPDGF-B for accelerating osseointegration while maintaining an acceptable safety profile.