rhBMP-2 Pre-Treated Human Periodontal Ligament Stem Cell Sheets Regenerate a Mineralized Layer Mimicking Dental Cementum

Abstract

The periodontal complex consisting of alveolar bone, cementum, and periodontal ligaments (PDL) supports human teeth through the systematic orchestration of mineralized tissues and fibrous tissues. Importantly, cementum, the outermost mineralized layer of dental roots, plays an essential role by bridging the inner ligaments from the dental root to the alveolar bone. When the periodontal complex is damaged, the regeneration of each component of the periodontal complex is necessary; however, it is still challenging to achieve complete functional regeneration. In this study, we tried to control the regeneration of cementum and PDL by using a human PDL stem cell (hPDLSC) sheet engineering technology with the pretreatment of recombinant human BMP-2 (rhBMP-2). Isolated hPDLSCs obtained from extracted human teeth were pretreated with rhBMP-2 for in vitro osteogenic differentiation and grafted on the micro/macro-porous biphasic calcium phosphate (MBCP) blocks, which represent dental roots. The MBCPs with hPDLSC sheets were implanted in the subcutaneous layer of immune-compromised mice, and rhBMP-2 pretreated hPDLSC sheets showed higher mineralization and collagen ligament deposition than the no-pretreatment group. Therefore, the rhBMP-2-hPDLSC sheet technique could be an effective strategy for the synchronized regeneration of two different tissues: mineralized tissue and fibrous tissues in periodontal complexes.

The recent advances in scaffolds for integrated periodontal regeneration

“…Most previous studies with biodegradable scaffolds have focused on the guided regeneration of CM and PDL [ 4 , 7 , 30 , 31 ]. Cho et al reported that CM-like tissue structure was formed on the surface of human dentin when incubated with human PDL stem/progenitor cells (PDLSCs) seeded in 3D-printed poly(ε-caprolactone) PCL scaffolds spatially delivered with connective tissue growth factor (CTGF), bone morphogenic protein 2 and 7 (BMP-2 and BMP-7) [ 31 ].…”

“…Chen et al fabricated an electrospun multiphasic scaffold which consisted of PCL, collagen type I (COL-I), and rhCEMP1/ACP that promoted formation of CM-like structure when implanted in rat calvaria with PDLSCs for 8 weeks [ 32 ]. Park et al performed a subcutaneous implantation of micro/macro-porous biphasic calcium (MBCP) blocks seeded with BMP-2 pre-treated PDLSCs into immunocompromised mice [ 7 ]. After 4 weeks, BMP-2 pre-treatment group showed formation of mineralized tissue integrated with fibrous tissues [ 7 ].…”

“…In support of the treatment for periodontally diseased tooth, various biomaterials have been applied starting as a contact inhibition membrane in the guided tissue regeneration (GTR) that is the current gold standard in dental clinic. Recently, various biomaterials have been prepared in a form of tissue engineering scaffold to facilitate the regeneration of damaged periodontal tissues [ [4] , [5] , [6] , [7] ]. From a physical substrate to support healing of a single type of periodontal tissue to multi-phase/bioactive scaffold system to guide an integrated regeneration of periodontium, technologies for scaffold fabrication have emerged in last years.…”

Tooth-Supporting Hard Tissue Regeneration Using Biopolymeric Material Fabrication Strategies

“…Cementum is the mineralized tissue layer on the tooth-root surface and plays the critical role of PDL functionalization by anchoring collagenous Sharpey’s fiber bundles to tooth-root dentin surfaces [ 14 , 21 , 22 , 23 , 24 ]. There are two major classifications of cementum: the acellular extrinsic fiber (acellular) cementum and the cellular intrinsic fiber (cellular) cementum [ 25 , 26 , 27 ].…”

“…However, periodontal tissue formations are extremely limited and unpredictable in terms of the regeneration process due to structural complications, hierarchical constructs with micron-scaled dimensions, and elaborate tissue integrations for a functioning restoration [ 3 , 47 ]. To overcome these limitations, various biologically achievable strategies in the regenerative medicine of periodontal tissues have recently been proposed for the restoration of lost tooth-supporting structures and multiple tissue integrations [ 21 , 48 , 49 , 50 , 51 , 52 ]. Moreover, computer-aided-design (CAD) technology has been utilized to design and manufacture biopolymeric scaffolding systems to attempt the spatiotemporal regeneration of periodontal tissues with structural integrations for tooth-supporting function restorations in preclinical situations [ 53 , 54 ].…”