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Year : 2017  |  Volume : 5  |  Issue : 2  |  Page : 35-38

Impact of tissue engineering in dentistry

1 Department of Prosthodontics, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India
2 Department of Pedodontics and Preventive Dentistry, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh, India

Date of Web Publication14-Nov-2018

Correspondence Address:
Dr. Pranitha Kakarla
Department of Pedodontics and Preventive Dentistry, Sibar Institute of Dental Sciences, Guntur, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/njecp.njecp_5_16

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As technology is advancing at a galloping rate, tissue engineering is no longer a fairy-like idea; it is turning out to be a reality. Tissue engineering has developed as the new frontier in the arena of dentistry. New technology will persistently have a major impact on dental practice, from the development of high-speed handpieces to modern restorative materials. Tissue engineering will extensively affect the dental practice significantly within the next 25 years. Regeneration of tissues and organs in humans after damage has remained as a hindrance throughout the antiquity to physicians, dentists, and patients. Hence, it will be in everyone's interest to welcome tissue engineering with open arms, but at the same time, to take it with a pinch of salt.

Keywords: Bone, periodontium, pulp, tissue engineering, tissue formation

How to cite this article:
Anche S, Kakarla P, Avula SS, Akkala SG. Impact of tissue engineering in dentistry. Niger J Exp Clin Biosci 2017;5:35-8

How to cite this URL:
Anche S, Kakarla P, Avula SS, Akkala SG. Impact of tissue engineering in dentistry. Niger J Exp Clin Biosci [serial online] 2017 [cited 2019 Sep 22];5:35-8. Available from: http://www.njecbonline.org/text.asp?2017/5/2/35/245406

  Introduction Top

Tissue engineering is relatively a new field of applied biological research. Langer and Vacanti in 1993 defined tissue engineering as “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain or improve tissue function or a whole organ."[1] The principal objective behind tissue engineering is to replace and reconstruct the tissue so as to alleviate pain and to restore mechanical stability and function.[2] Tissue engineering also referred to as “regenerative dentistry” as the goal behind it is also to restore tissue function through the delivery of stem cells, bioactive molecules, or synthetic tissue constructs engineered in the laboratory.[3] Seeing the current prevalence of the dental diseases, it will be a challenge and resource burden of restoring lost tissue. Therefore, the purpose of this brief review is to provide a knowledge on tissue engineering, educate the profession on its effectiveness, and potential disadvantages, its accomplishments in dentistry and its future promises.

  Strategies to Engineer Tissue Top

If the question arises: what is the ideal replacement of lost tissues? The gold standard to replace an individual's lost or damaged tissue is the same natural, healthy tissue. This led to the concept of engineering or regenerating the new tissue from preexisting tissue.[4] To engineer a tissue, strategies can be categorized into three major classes: Conductive, inductive, and cell transplantation approaches, which utilizes a material component with different goals.

In conductive approach, the biomaterials are used in a passive manner to facilitate the growth or regenerative capacity of existing tissue. It has been revolutionized by widespread application of a conductive approach in restorative and prosthetic dentistry by osseointegration of the dental implant for replacing multiple and single teeth. Brånemark et al. were the first to effectively achieve this phenomenon, in which the application is relatively simple, and the armamentarium does not include living cells or diffusible biological signals.[5] Another example of conductive approach that is widely used in dentistry is guided tissue regeneration (GTR). Nyman et al. successfully utilized the osteoconductive mechanisms for selective wound healing by supporting the ingrowth of the periodontal supporting cells, while excluding gingival epithelial and connective tissue cells from reconstruction sites.[6]

In contrast, inductive approach activates the cells near the defect site with specific biological signals. The origin of this mechanism is rooted in finding the defined molecules termed as growth factors. Urist in 1965 was the first who revealed that the new bone could be induced at nonmineralized sites after implantation of powdered bone, that contained proteins identified as bone morphogenetic proteins (BMPs).[7] These proteins have been used in many clinical trials that include regeneration and repair of bone as in nonhealing fractures and periodontal disease.

The limitation with inductive approach is that inductive factors are not known for a specific tissue, when a large tissue mass or organ is needed or when tissue replacement must be immediate. In this condition, the third tissue engineering approach, cell transplantation became very apt. However, this approach requires the needed cells to be expanded in the laboratory and also requires the clinician or surgeon, the cell biologist, and the bioengineer to engineer a tissue.[8]

  Applications in Dentistry Top

Approach of tissue engineering in the oral cavity has significant advantages when compared to other sites in the body because of easy access and observability. Potential applications for tissue engineering therapies in the oral and maxillofacial complex include the delivery of growth factors for periodontal regeneration, pulp capping/dentin regeneration, treatment of salivary gland damage, regeneration for bone grafting of large osseous defects in dental and craniofacial reconstruction (e.g., bone augmentation prior to prosthetic reconstruction, fracture repair and repair of facial bone defects secondary to trauma, tumor resection, or congenital deformities) and articular cartilage repair.[9]

Salivary gland

Is it essential to construct an artificial salivary gland? The answer obviously lies in filling a clinical need. Although most research work in tissue engineering has focused on tissues whose loss or failure will lead to the patient's death (e.g., the liver or endocrine pancreas), there are many circumstances involving the tissue loss that is nonlife-threatening, yet that markedly affect quality of life (e.g., patients receiving ionizing radiation for head-and-neck cancer and patients with Sjogren's Syndrome experience irreversible salivary gland damage).[10] Without saliva, these patients experience dysphagia, rampant caries, mucosal infections, and considerable oral discomfort. Patients receiving IR or those with SS, experience complete gland destruction and cannot utilize pharmacological tools (sialogogues) and are not candidates for gene therapy; they require the presence of some surviving epithelial tissue.[11] Hence, the researchers have been motivated to develop an orally implantable fluid secretory device and this simple device, a “blind-end” tube, is suitable to engraft in the buccal mucosa of patients whose salivary parenchyma has been destroyed. The lumen of these tubes would be lined with compatible epithelial cells and be physiologically capable of unidirectional water movement, which could be effective in treating conditions associated with salivary gland dysfunction.[12]


Cartilage destruction associated with trauma and a number of diseases have opened a new door to cartilage reconstruction (e.g., nasal septum, temporomandibular joint) with the design of polymer scaffolds with defined mechanical and degradative properties. The limited capacity of cartilaginous tissue to regenerate and the lack of inductive molecules have focused interest among researchers in developing cell transplantation approaches to engineer a cartilage. Transplantation of cells without a carrier to repair small articular cartilaginous defects is now used clinically. Investigators also reported that new cartilaginous tissue with precisely defined sizes and shapes are used for maxillofacial reconstruction in animal models.[13]

Bone regeneration

Bone regeneration in the craniomaxillofacial skeleton has undergone many advances as bony defects due to injury, disease, and congenital disorders represent a major health problem. Autografts, allografts, xenografts, and synthetic biomaterials are used options to treat large bone defects. Though they restore stability and function to a reasonably sufficient degree, they still contain limitations. This has led to an interest in engineering a bone.[14] GTR after periodontal surgery represents a conductive approach to regenerate small bony defects. In situations where GTR is not sufficient, BMPs, related proteins and the genes encoding these proteins allow to engineer a bone using inductive approach. In contrast, cell transplantation approaches offer the possibility of preforming large bone structures (e.g., complete mandible).[13] Another example is distraction osteogenesis that makes use of endogenous tissue engineering for promotion of bone formation. The first translation to intramembranous bone of the craniofacial skeleton was proven in 1972 using a canine model and McCarthy (1992) implemented the first human mandibular distraction. Despite ever-increasing experience, significant complications continue to plague surgeons performing this procedure are soft-tissue infections, osteomyelitis, patient discomfort, and incompliance also contribute to overall morbidity.[15]

Periodontal regeneration

Tissue engineering concept in periodontics began with GTR, a mechanical approach utilizing nonresorbable membranes to regenerate periodontal defects. The management of periodontal defects includes bone grafts, root conditioning, and polypeptide growth factors.[16]

To engineer a tissue, the main requirements are appropriate progenitor cells, signaling molecules, an extracellular matrix, or carrier and an adequate blood supply. Periodontal regeneration involves cells such as epithetlial cells, fibroblasts, osteoblastic cells, junctional epithelium, gingival fibroblasts, periodontal ligament fibroblasts, osteoblasts, alveolar bone cells, cementoblasts, and signaling molecules such as growth factors Fibroblast growth factor 1 and 2, BMPs, insulin-like growth factor-I and II (IGF-1 and II), adhesion molecules (Fibronectin, laminin, osteopontin, collagens, and cementum attachment protein) and structural proteins (Types I, III, V, XII, and XIV collagens, proteoglycans, osteocalcin, tenasin, enamel matrix proteins) and scaffolds (e.g., collagen, bone minerals, synthetics, and extracellular matrix) to engineer a damaged tissue.[17]

Cell therapy has also been employed in periodontal surgery which involves a cell expansion strategy in an ex vivo environment followed by transplantation back into the defect area. Tissue-banked human fibroblasts or patient's connective tissue from attached gingiva of the retromolar area is harvested on a collagen/silicone bilayer membrane which later could be used as a donor tissue.[16]

The world of medicine has acquainted with the regenerative potential of platelets in 1974. However, recently, these platelet concentrates have been used for the improvement of reparation and regeneration of the soft and hard tissues after various periodontal surgical procedures. These platelets concentrate paved a way to accelerate and enhance the body's natural wound healing mechanisms.[18]

Platelet-rich plasma was introduced for the first time by Marx et al. (1998). This was used as a method of introducing concentrated growth factors platelet-derived growth factor, transforming growth factor-beta, and IGF-1 to the surgical site, thereby enriching the natural blood clot in order to hasten wound healing and stimulate bone regeneration. A natural human blood clot consists of 95% red blood cells (RBCs), 5% platelets, <1% white blood cells (WBCs), and numerous amounts of fibrin strands. A PRP blood clot, on the other hand, contains 4% RBCs, 95% platelets, and 1% WBCs. The PRP preparation protocol requires collection of blood with anticoagulant, centrifugation in two steps, and induced polymerization of the platelet concentrate using calcium chloride and bovine thrombin.[19] Platelet-rich fibrin is a second-generation platelet derivative, developed in France by Choukroun et al. (2001). Unlike PRP, this technique does not require anticoagulants nor bovine thrombin or any other gelifying agent, and it is strictly autologous fibrin matrix containing a large quantity of platelet and leukocyte cytokines. These platelet concentrates have been clinically used in the fields of dermatology, orthopedics, dentistry, and ophthalmology.[20]

Dentin and dental pulp

The regeneration of dentin is feasible as dentin is in intimate contact with an underlying highly vascular and innervated pulpal tissue, forming a tightly-regulated “dentin-pulp complex."[21] Decay of tooth leads to loss of odontoblasts, in such conditions the engineered tissues have a great potential to induce formation of new cells from pulp tissue using certain BMPs, inturn these new odontoblasts can synthesize new dentin.[22] Studies also revealed that tissue engineering of dental pulp itself may also be possible from dental pulp stem cells. Further studies also confirm that the differentiation of stem cells as well as angiogenesis and neurogenesis are essential for pulp regeneration. Therefore, scaffolds, cells, and bioactive molecules are essentially needed for dental tissue engineering.[23] Further, development and successful application of these strategies to regenerate dentin and dental pulp could 1 day revolutionize the treatment of our most common oral health problem, caries.

Areas of research that might have application in the development of regenerative endodontic techniques include Root canal revascularization through blood clotting, pulp implantation, postnatal stem cell therapy, Scaffold implantation, injectable scaffold delivery, three dimensional cell printing, and gene therapy. The responses in pulp also include neural and vascular regeneration. Despite the impressive progress in tissue engineering approaches toward regenerative pulp therapy, numerous challenges still remain.[21]

  Future Concerns in the Field of Tissue Engineering Top

In the coming future, advances in bioengineering research will lead to the wide application of the regenerative dentistry in general dental practice to produce wonderful treatments and dramatically improve patient's quality of life. The impact of tissue engineering will yield numerous clinical benefits that include improved treatments for periodontal defects, enhanced maxillary and mandibular grafting procedures and biological methods to repair teeth after carious damage and possibly even regrowing lost teeth.

To alleviate the clinical problems, it is necessary for the tissue-engineered products to be manufactured reliably. This need is almost self-evident but worthy of emphasis. The successful research raises numerous concerns for future feasibility of scaling up from research levels to industrial output that include batch-to-batch repeatability in production, methods to achieve and maintain sterility, tissue procurement for cell preparations, and optimal handling and storage methods. These specifics must be addressed for each product individually.

Another concern is that for many tissue-engineered products, viable cells are an essential component. Unless, a patient's own cells can be amplified in an adequate and timely manner, enabling them to be used in the tissue-engineered device is not possible, then the cells must be derived from another tissue. This situation, in turn, raises a number of significant ethical issues. There is much of a debate among researchers in the biomedical community about the ethical concerns related to these tissue-engineered products. An additional and important consideration in the application of these new technologies is the cost associated with each device.

Behind the controversy surrounding tissue engineering, humankind is proceeding beyond the ability to create inanimate objects, toward the capability of replacing and regenerating the own living body tissues. The amalgamation of bioengineering and dentistry will result in an explosion of knowledge that will enhance our understanding of the cell and molecular basis for regeneration of tooth structures and culminate a new era in dentistry, enabling us to restore lost tissue function.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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Brånemark PI, Adell R, Breine U, Hansson BO, Lindström J, Ohlsson A, et al. Intra-osseous anchorage of dental prostheses. I. Experimental studies. Scand J Plast Reconstr Surg 1969;3:81-100.  Back to cited text no. 5
Nyman S, Lindhe J, Karring T, Rylander H. New attachment following surgical treatment of human periodontal disease. J Clin Periodontol 1982;9:290-6.  Back to cited text no. 6
Urist MR. Bone: Formation by autoinduction. Science 1965;150:893-9.  Back to cited text no. 7
Krebsbach PH, Kuznetsov SA, Bianco P, Robey PG. Bone marrow stromal cells: Characterization and clinical application. Crit Rev Oral Biol Med 1999;10:165-81.  Back to cited text no. 8
Grande DA, Breitbart AS, Mason J, Paulino C, Laser J, Schwartz RE, et al. Cartilage tissue engineering: Current limitations and solutions. Clin Orthop Relat Res 1999; 367:S176-85.  Back to cited text no. 9
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Baum BJ, O'Connell BC. The impact of gene therapy on dentistry. J Am Dent Assoc 1995;126:179-89.  Back to cited text no. 11
Baum BJ, Wang S, Cukierman E, Delporte C, Kagami H, Marmary Y, et al. Re-engineering the functions of a terminally differentiated epithelial cell in vivo. Ann N Y Acad Sci 1999;875:294-300.  Back to cited text no. 12
Kaigler D, Mooney D. Tissue engineering's impact on dentistry. J Dent Educ 2001;65:456-62.  Back to cited text no. 13
Oryan A, Alidadi S, Moshiri A, Maffulli N. Bone regenerative medicine: Classic options, novel strategies, and future directions. J Orthop Surg Res 2014;9:18.  Back to cited text no. 14
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Siddhartha VA, Sarthak B, Rashmi G, Shilpa S, Uzma B. Tissue engineering in periodontics – A novel therapy. Ann Dent Res 2012;2:1-7.  Back to cited text no. 16
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Gupta V, Bains VK, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: literature review. Asian J Oral Health Allied Sci 2011;1:22-8.  Back to cited text no. 18
Bielecki T, Dohan Ehrenfest DM. Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF): Surgical adjuvants, preparations for in situ regenerative medicine and tools for tissue engineering. Curr Pharm Biotechnol 2012;13:1121-30.  Back to cited text no. 19
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