An in-vivo Intraoral Defect Model for Assessing the Use of P11-4 Self-Assembling Peptide in Periodontal Regeneration

Abstract

Periodontal disease is one of the most common diseases worldwide. It has a significant impact on oral health and subsequently the individual's quality of life. However, optimal regeneration of periodontal tissues, using current treatments, has yet to be achieved. Peptide self-assembly has provided a step-change in nanobiotechnology and regenerative medicine fields. Our aim was to investigate the effects of a selfassembling peptide (SAP; P 11-4) on periodontal regeneration in a preclinical model. Twenty-six bilateral maxillary critical-sized periodontal defects were created surgically in 13 rats. Defects on one side of the mouth were filled with P 11-4 hydrogel; the contralateral defect was untreated (control). Rats were sacrificed immediately post-surgery (time 0) and after 2 and 4 weeks. Retrieved maxillae were processed for histological, immunohistochemical, and histomorphometric assessments. The results of histological analysis showed greater organization of periodontal fibers in defects treated with P 11-4, at both time points, when compared to untreated defects. Histomorphometry showed that treated defects had both a significant increase in functional periodontal ligament length and a reduction in epithelial down growth after 4 weeks. At 2 weeks, treated defects showed a significant increase in expression of osteocalcin and osteoprotegerin as judged by immunohistochemistry. Also, a significantly higher osteoprotegerin/RANKL ratio was shown in treated defects. In conclusion, the results demonstrated enhanced regeneration of periodontal tissues when SAP P 11-4 was used to fill periodontal defects in rats. The findings of this study suggest that SAP P 11-4 is a promising novel candidate for periodontal regenerative therapy. Further investigations are required for optimization before clinical use.

Efficacy and safety of P11-4 for the treatment of periodontal defects in dogs

“…Furthermore, SAPM P 11 -4 recently was found to enhance proliferation of dental follicle stem cells, osteogenic differentiation and expression of Collagen Type I in vitro [ 10 ]. In addition, the present study also supports the results obtained in the first animal study investigating SAPM P 11 -4 in the treatment of periodontal disease [ 14 ] where SAPM P 11 -4 treated critical defects showed enhanced formation of Sharpey’s fibres compared to the untreated critical control defects. Favourable cellular interactions between the SAP P 11 -4 scaffold, mediated by fibronectin and other extracellular matrix proteins such as Collagen Type I, III and Fibrillin I absorbed at the scaffold’s surface, and human periodontal ligament fibroblasts led to the observed migration of the periodontal ligament fibroblasts within the SAP P 11 -4 matrix [ 12 , 13 ] and may contributes to the enhanced formation of periodontal attachment in comparison to the sham-operated control in the present study (T1 group).…”

“…The present preclinical study in dogs confirms the results previously obtained by Burke [ 35 ] and Saha [ 34 ] that SAPM P 11 -4 is a suitable scaffold for bone regeneration based on the regeneration of alveolar bone’s height, volume and mineral density which were comparable to the gold standard EMD. SAPM P 11 -4 may positively influence osteoblasts and their activity enabling enhanced bone growth as a significant higher OPG (osteoprotegrin) / RANKL (Receptor Activator of NF-κB Ligand) ratio was found for SAPM P 11 -4 treated periodontal defects in rats compared to untreated control defects [ 14 ]. Furthermore, SAPM P 11 -4 recently was found to enhance proliferation of dental follicle stem cells, osteogenic differentiation and expression of Collagen Type I in vitro [ 10 ].…”

“…El-Sayed et al [ 14 ] were the first to study SAPM P 11 -4 for the treatment of periodontal disease in vivo. Bilateral maxillary critical-sized periodontal defects were generated in 13 rats.…”

A bilayered tissue engineered in vitro model simulating the tooth periodontium

“…Self-assembling peptide P11-4, a smart scaffold, was successfully used to regenerate critical PDL defects in a rat model (El-Sayed et al, 2020). The same scaffold was used by Koch et al, 2020 to develop a 3D PDL model.…”

“…This approach will require the use of different biomaterials to represent hard tissue and soft tissue components of the periodontium (Chen et al, 2008). The diversity of the surface topography of the materials will play a role in directing the differentiation route of the cells (Elisseeff et al, 2005;Jäger et al, 2006). Furthermore, mechanical characterisation of multiphasic constructs is essential in future applications of such models (Sabree et al, 2015).…”