|Year : 2013 | Volume
| Issue : 4 | Page : 118-121
Combining 3-dimensional degradable electrostatic spinning scaffold and dental follicle cells to build peri-implant periodontium
Ximu Zhang1, Xiaoyan Zhou2, Deyu Hu1
1 State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China
2 Faculty of Dentistry, Institute of Dental Research, Westmead Millennium Institute and Centre for Oral Health, Westmead Hospital, The University of Sydney, New South Wales, Australia
|Date of Web Publication||4-Dec-2013|
State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu-610 041, China
Source of Support: None, Conflict of Interest: None
Introduction: Some inevitable problems, such as concentrated bite force and lacked ability of self-renewal, are proved to be the major challenge in the management of implants failures. Thus, it is meaningful to find an ideal dental implant harboring its own peri-implant periodontium, just as the natural teeth. Various studies attempted to reconstruct the periodontium around implants, but unfortunately, it was previously revealed that the artificial periodotium around implants was just a wilderness of fibers, while without the physiological function of natural periodontium, like sensory and homeostatic. The Hypothesis: In this paper, we propose a hypothesis that a modified three-dimensional scaffold with reconstructed peri-implant tissues can be a network for stem cells differentiation. After seeded on the scaffold, stem cells produce various growth factors and differentiate to different orientations in places necessary. This hypothesis, if proven to be valid, will offer a novel and effective therapy for the restoration of missing teeth by implant. Evaluation of the Hypothesis: The scaffold involves three different tissues. Though degradation rate of electrospinning scaffold is under control, its degradation rate should be in consistent with the generation of three tissues. Therefore, the relative experiments are necessary to define the best rate of degradation. Further verification is necessary to check whether the rebuilt cementum, bone and periodontium are strong enough to keep the implant stable and maintain its function.
Keywords: 3-D electrostatic spinning scaffold, dental follicle cells, dental implant, electrospinning scaffold, peri-implant periodontium, stem cells
|How to cite this article:|
Zhang X, Zhou X, Hu D. Combining 3-dimensional degradable electrostatic spinning scaffold and dental follicle cells to build peri-implant periodontium. Dent Hypotheses 2013;4:118-21
|How to cite this URL:|
Zhang X, Zhou X, Hu D. Combining 3-dimensional degradable electrostatic spinning scaffold and dental follicle cells to build peri-implant periodontium. Dent Hypotheses [serial online] 2013 [cited 2019 Dec 13];4:118-21. Available from: http://www.dentalhypotheses.com/text.asp?2013/4/4/118/122672
| Introduction|| |
Tooth loss due to decay, trauma, or periodontitis is a common and frequently occurring disease in human. Traditionally, lost teeth are replaced by artificial dentures, such as removable partial dentures and fixed partial. However, the high failure rate of artificial dentures has been attributed to the development of caries, periodontal diseases, and endodontic pathology. Oral implantology has been developed rapidly in the recent 40 years. The implant involves a kind of artificial root shaped titanium that is used as a substitute for the root of the tooth. Osseointegrated dental implant introduced by Bränemark has become a routinely recommended procedure in the clinical practice of implant dentistry.  However, osseointegration means the direct structural and functional connection between living bone and the surface of a load-bearing artificial implant, lacking periodontium. This connection is different from the periodontal ligament (PDL) around the roots of the teeth. Moreover, the implant-bone interface lack of physiological buffer can easily lead to bite forces concentrated, causing potential damage to alveolar bone, implant, and even temporomandibular joint. ,, Therefore, the ideal dental implant should harbor its own peri-implant periodontal tissue with physiological functions as the natural tooth, , and it appears to be an urgent need for the concept of periodontal tissue regeneration around dental implants.
| The Structure and Function of Natural Periodontium|| |
Alveolar bone, PDL, and root cementum constitute periodontium which plays an important role in supporting teeth, buffering chewing forces, and maintaining integrity of masticatory mucosa in oral cavity.
PDL is a specialized connective tissue that connects cementum and alveolar bone together to maintain and support teeth in situ. It consists of small tough elastic fibers that keep teeth attaching to the jaw. These fibers help tooth to withstand the naturally substantial compressive forces which occur during chewing and remain embedded in the bone. Cementum is a special mineralized tissue that covers the entire root surface as a layered structure. The bone around tooth root is lamellar bone. The ends of PDL fibers are buried both in alveolar bones and cementum, which makes teeth firmly fixed in the socket. Besides alveolar bone, PDL, and cementum; there are also kinds of nerve fibers around teeth, which play an important role in sensing bite forces and helping reducing overloading. In order to help supporting, sensing, nourishing, and homeostating; ideal peri-implant periodontium should also involve cement, PDL and bone, and nerve fibers if possible. Stem cells can be induced to differentiate into diverse specialized cell types, however, complete control of stem cell differentiation from pluripotent to fully specialized cell would be a great challenge, since it requires multiple growth factors in defined order and quantity, and at defined time intervals.
| The Hypothesis|| |
We propose a hypothesis as follows
A modified in vivo three dimensional (3-D) scaffold with reconstructed structure of periodontium, can be a network for stem cells differentiation. After seeded on the scaffold, stem cells produce various growth factors and differentiate to different orientations in places necessary, just like the periodontium development process. In keeping with this assumption, we postulate a hypothesis for the reconstruction of periodontal tissues around the implant in a challenging novel approach:
A 3-D polylactic-co-glycolic acid (PLGA) degradable scaffold is constructed into three different layers like a sandwich structure by electrospum. The upper layer is formed by randomly oriented fibrous PLGA, and the middle layer is a membrane fabricated with parallel and cross-aligned fibrous PLGA. 
Coat this scaffold on titanium dental implant. Dental follicle (DF) cells from the extracted impacted wisdom teeth are cultivated in vitro and seeded into the implant socket. After that, the implant is subjected to a mild loading following the combination with the cells, which is of great importance for the function stimuli to the peri-implant tissues during the healing process. Finally, the structure and function of the periodontal reconstruction is observed by 6 months later. Details of the hypothesis approach are illustrated in [Figure 1].
|Figure 1: Diagrams of approaches for peri-implant periodontium reconstruction. (a) Use electrospinning technology to make polylactic-coglycolic acid (PLGA) three-dimensional (3-D) degradable scaffold. (b) Coat dental implant with this scaffold. (c) Culture dental follicle (DF) cells in vitro. (d) Transfer DF cells into the implant socket. (e) Implant coated implant. (f) Several months later, peri-implant periodontal tissue will be observed. (g) The ideal peri-implant periodontium tissue we hope to form: 1. Bone, 2. well-ordered periodontal ligament (PDL) fiber, 3. cement, and 4. nerve fiber|
Click here to view
| Evaluation of the Hypothesis|| |
DF surrounding the developing tooth germ is an ectomesenchymal tissue composed of various cells derived from the cranial neural crest.  They harbor precursor cells  for the tooth supporting apparatus and play a crucial role in the development of cementum, PDL, and alveolar bone. In 2009, Völlner F, et al. used a two-step strategy to induce DF cells into expose neural-like cell morphology with small neurite-like cell extrusions.  Given the fact that development of biological tooth occurs via a similar process to that of a natural tooth, two populations of stem cells are most likely to be involved: Epithelial stem cells (EpSC), which give rise to ameloblasts, and mesenchymal stem cells (MSC) which possess potential to differentiate into the odontoblasts, cementoblasts, osteoblasts, and fibroblasts of the PDL. DF cells, considered as one kind of MSC, have been showed to be one attractive candidate cell line, because it is relatively easier to obtain DF cells from supernumerary teeth, deciduous teeth, and wisdom teeth; which are often extracted for physiological, medical, or cosmetic reasons and preserved for future need. Moreover, compared with bone marrow-derived MSCs, DF cells are more closely related to dental tissues.
In 2009, Yang et al., used MSCs-seeded small intestinal submucosa to repair chronic myocardial infarction without any cytokine stimulation. Immunofluorescence staining demonstrated the migration of MSCs from the membrane into the infarcted area and their differentiation to cardiomyocytes and smooth muscle cells. They claimed that various growth factors and stem cells homing factor were produced by MSCs through a paracrine action.  Based on this well-defined result, we hypothesized that DF cells, cultured on 3-D scaffold in vivo even without cytokine, could produce kinds of growth factors and stem cell homing factors, that is, endothelial microparticles (EMP), bone morphogenic proteins (BMP) and fibroblast growth factor (FGF), through a paracrine action or autocrine action, and the cells can differentiate into fibroblasts, osteoblasts, and cementoblasts in places where necessary.
Electrospinning has gained widespread interest as a potential polymer processing technique adopted in tissue engineering for the last decade. The electrospinning process affords the opportunity to engineer scaffolds with micro to nanoscale topography and high porosity similar to the natural extracellular matrix (ECM).  By using a stationary or rotating collector, either randomly oriented or aligned fibers can be formed, respectively. So far, electrospun scaffolds have been employed in a number of different tissue applications including: Vascular,  bone,  neural, , and tendon/ligament.  It is envisioned that for the regeneration of highly organized structures, like tendon and ligaments, only aligned fibrous scaffolds can provide adequate topographic guidance to cells. Shang et al.,  used the electrospin method to fabricated parallel and cross-aligned fibrous PLGA scaffolds and studied their effects on the growth behavior of rat PDL cells. They found that aligned scaffolds seemed to be able to promote the organized regeneration of periodontal tissue. Additionally, Inanc et al., found that human ligament fibroblasts presented higher cell adhesion, viability, and osteogenic differentiation properties when they were seeded on electrospun nanofiber PLGA scaffold as compared to the randomly oriented nanofiber.  It has been found that electrospun scaffold can be made of various materials, including biodegradable materials. PLGA, whose degradation products exhibit a weaker acidity than other materials. Furthermore, the rate of degradation can be controlled to some extent to coincide with the rate of new tissue formation, by altering parameters such as polymer blends, and ratio of amorphous to crystalline segments. 
| Discussion|| |
If this hypothesis is feasible, it will offer a novel and effective therapy for both missing teeth restoration by dental implant, and root exposure associated with chronic periodontitis, because the 3-D scaffold and stem cells combination can be coated on the exposed roots surface in the same way.
Besides things mentioned above, we are aware that some details need further discussion.
- In our hypothesis, the scaffold involves three different tissues. Though degradation rate of electrospinning scaffold is under control, its degradation rate should be in consistent with the generation of three tissues. Therefore, the relative experiments are necessary to define the best rate of degradation.
- An early mild load is very important for the functional stimuli to the peri-implant tissue. The amount and the time and manner to give a load require more explorations.
- There was one study  revealing cementum formation around a titanium implant. However, further verification is necessary to check whether the rebuilt cementum, bone, and periodontium are strong enough to keep the implant stable and maintain its function.
| References|| |
|1.||Barone A, Orlando B, Cingano L, Marconcini S, Derchi G, Covani U. A randomized clinical trial to evaluate and compare implants placed in augmented vs. Non-augmented extraction sockets: 3-year results. J Periodontol 2012;83:836-46. |
|2.||Lang NP, Berglundh T. Working Group 4 of Seventh European Workshop on Periodontology. Periimplant diseases: Where are we now? - Consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol 2011;38:178-81. |
|3.||Ormianer Z, Ben Amar A, Duda M, Marku-Cohen S, Lewinstein I. Stress and strain patterns of 1-piece and 2-piece implant systems in bone: A 3-Dimensional finite element analysis. Implant Dent 2012;21:39-45. |
|4.||Koka S, Zarb G. On osseointegration: The healing adaptation principle in the context of osseosufficiency, osseoseparation, and dental implant failure. Int J Prosthodont 2012;25:48-52. |
|5.||Mensor MC, Ahlstrom RH, Scheerer EW. Compliant keeper system replication of the periodontal ligament protective damping function for implants: Part I. J Prosthet Dent 1998;80:565-9. |
|6.||Mensor MC, Ahlstrom RH, Scheerer EW. Compliant Keeper system replication of the periodontal ligament protective damping function for implants: Part II. J Prosthet Dent 1999;81:404-10. |
|7.||Shang S, Yang F, Cheng X, Walboomers XF, Jansen JA. The effect of electrospun fibre alignment on the behaviour of rat periodontal ligament cells. Eur Cell Mater 2010;19:180-92. |
|8.||Kémoun P, Laurencin-Dalicieux S, Rue J, Farges JC, Gennero I, Conte-Auriol F, et al. Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro. Cell Tissue Res 2007;329:283-94. |
|9.||Yao S, Pan F, Prpic V, Wise GE. Differentiation of stem cells in the dental follicle. J Dent Res 2008;87:767-71. |
|10.||Völlner F, Ernst W, Driemel O, Morsczeck C. A two-step strategy for neuronal differentiation in vitro of human dental follicle cells. Differentiation 2009;77:433-41. |
|11.||Tan MY, Zhi W, Wei RQ, Huang YC, Zhou KP, Tan B, et al. Repair of infarcted myocardium using mesenchymal stem cell seeded small intestinal submucosa in rabbits. Biomaterials 2009;30:3234-40. |
|12.||Gillette BM, Rossen NS, Das N, Leong D, Wang M, Dugar A, et al. Engineering extracellular matrix structure in 3D multiphase tissues. Biomaterials 2011;32:8067-76. |
|13.||Hajiali H, Shahgasempour S, Naimi-Jamal MR, Peirovi H. Electrospun PGA/gelatin nanofibrous scaffolds and their potential application in vascular tissue engineering. Int J Nanomedicine 2011;6:2133-41. |
|14.||Cai YZ, Zhang GR, Wang LL, Jiang YZ, Ouyang HW, Zou XH. Novel biodegradable three-dimensional macroporous scaffold using aligned electrospun nanofibrous yarns for bone tissue engineering. J Biomed Mater Res A 2012;100:1187-94. |
|15.||Xie J, MacEwan MR, Schwartz AG, Xia Y. Electrospun nanofibers for neural tissue engineering. Nanoscale 2010;2:35-44. |
|16.||Wang G, Hu X, Lin W, Dong C, Wu H. Electrospun PLGA-silk fibroin-collagen nanofibrous scaffolds for nerve tissue engineering. In Vitro Cell Dev Biol Anim 2010;47:234-40. |
|17.||James R, Toti US, Laurencin CT, Kumbar SG. Electrospun nanofibrous scaffolds for engineering soft connective tissues. Methods Mol Biol 2011;726:243-58. |
|18.||Inanç B, Arslan YE, Seker S, Elçin AE, Elçin YM. Periodontal ligament cellular structures engineered withelectrospun poly (DL-lactide-co-glycolide) nanofibrous membrane scaffolds. J Biomed Mater Res A 2009;90:186-95. |
|19.||Kim K, Yu M, Zong X, Chiu J, Fang D, Seo YS, et al. Control of degradation rate and hydrophilicity in electrospun non-woven poly (D, L-lactide) nanofiber scaffolds for biomedical applications. Biomaterials 2003;24:4977-85. |
|20.||Guarnieri R, Giardino L, Crespi R, Romagnoli R. Cementum formation around a titanium implant: A case report. Int J Oral Maxillofac Implants 2002;17:729-32. |