Tissue engineering: state of the art in oral rehabilitation

Abstract

More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering.

Fig. 1

The Tissue Engineering Triad (228). The three main design components in tissue engineering are based on the three main components of tissues: cells, their extracellular matrix (scaffolds) and a signalling system. Each of these components represents a design strategy, cell transplantation, conduction and induction, respectively, which can be used individually or in combination to optimize regeneration and engineering of a functional tissue [Figure reprinted with permission from (228)]. In this review, several specific design considerations for each component have been highlighted. Throughout the text, these considerations and their implications for oral tissue engineering will be explored.

Fig. 2

Tissue Engineering in Practice – Temporomandibular Joint (30). (a) Image-based design of a theoretical site-specific implant for temporomandibular joint engineering using solid free-form fabrication. (b) A composite scaffold consisting of PLLA was seeded with differentiated porcine chondrocytes and hydroxyapatite (HA) seeded with Ad.BMP7 transduced gingival fibroblasts was implanted subcutaneously into immunocompromised mice. (c) Four weeks post-transplant harvested implants were sectioned and analysed for presence of osteo-chondral structures. Cartilage (arrows) and bone (*) were observed separated by a defined interface (dotted line) [Adapted with permission from (30)].

Fig. 3

Tissue Engineering in Practice – Oral Mucosa (202). Tissue engineered dermal replacement DermaGraft^™ was used in place of autologous tissue for vestibuloplasty post-squamous cell carcinoma removal. (a) Post-surgical scars limited patient closure. (b) Intraoral view shows insufficient vestibular depth with extensive fibrous and muscular insertion. (c) Mucogingival junction and periosteal dissection was followed by implantation of Dermagraft^™. (d) Patient demonstrating improved vestibular depth after 3 months. [Reprinted with permission from (202)].