Pre-clinical models for oral and periodontal reconstructive therapies

Abstract

The development of new medical formulations (NMF) for reconstructive therapies has considerably improved the available treatment options for individuals requiring periodontal repair or oral implant rehabilitation. Progress in tissue engineering and regenerative medicine modalities strongly depends on validated pre-clinical research. Pre-clinical testing has contributed to the recent approval of NMF such as GEM 21S and INFUSE bone grafts for periodontal and oral regenerative therapies. However, the selection of a suitable pre-clinical model for evaluation of the safety and efficacy of a NMF remains a challenge. This review is designed to serve as a primer to choose the appropriate pre-clinical models for the evaluation of NMF in situations requiring periodontal or oral reconstruction. Here, we summarize commonly used pre-clinical models and provide examples of screening and functional studies of NMF that can be translated into clinical use.

Figures

Figure 1.

Rat periodontal fenestration defect. (a) The fenestration defect was created on the buccal surface of the mandibular alveolar bone. Distal and buccal roots of the first molar and the buccal root of the second molar were exposed. Novel medical formulations (NMF in sky-blue) were delivered into the defect. (b) The coronal section of the alveolar bone shows the defect outline. The cemental layer, superficial dentin, and the periodontal ligament were removed. At 3, 10, 21, and 35 days post-surgery, tissue samples were harvested, and the regeneration of bone and cementum was evaluated. Adapted from King et al., 1997.

Figure 2.

Infrabony peri-implant defect in the rat. (a) After extraction of the maxillary first molar, the socket was allowed heal for ~ 4 wks. (b) During the second surgery, a bone defect was created by means of an osteotomy in the location of the former tooth. An implant (1 mm x 2 mm) was press-fit into position, and the NMF was delivered to the peri-implant bone defect, followed by soft-tissue wound closure. (c) At multiple time-points (10, 14, and 21 days), tissue samples were harvested, and bone healing was evaluated.

Figure 3.

Vertical bone augmentation in rat (capsule model). (a,b) The Teflon capsule was positioned on the vestibular surface of the mandibular ramus and stabilized by means of sutures. (c) The pattern of bone neogenesis included the deposition of loose granulation tissue, subsequently replaced by osteoid and new bone. The newly formed mineralized tissue was in close contact with the original bone of the mandibular ramus. An acellular region was noted superior to the surface of the granulation tissue. Tissue samples were harvested from 2 to 6 mos, and bone neogenesis was evaluated.

Figure 4.

Supra-alveolar periodontal defect in the canine. (a) Alveolar bone was removed around the 3rd and 4th premolar teeth to create a horizontal defect 4-6 mm from reduced bone to the fornix of the furcation. Notches on the internal root surfaces were created at the level of the reduced bone. (b) The furcation lesion was filled with the NMF, and the soft tissues were coronally advanced to cover the defect. Tissue samples were harvested at 4, 8, and 12 wks after surgery. (c) Formation of new periodontal ligament (PDL), new cementum (NC), and new bone (NB) was evaluated in the furcation region. D: dentin.

Figure 5.

Supra-alveolar peri-implant defect in the canine. Approximately 6 mm of alveolar bone was removed around mandibular premolar teeth as measured from the CEJ. (a) After extraction of the premolar teeth, implants were positioned in the osteotomies prepared in the extraction site. Implants were primarily stably contained within 5 mm of native alveolar bone. (b) NMF was delivered around the exposed implants, and the soft tissues were positioned to cover the implant fixtures. (c) Tissue samples were harvested, and the regenerated bone was evaluated at 2, 4, and 6 mos post-surgery.