Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering

Abstract

Current treatments for diseases and trauma of dental, oral and craniofacial (DOC) structures rely on durable materials such as amalgam and synthetic materials, or autologous tissue grafts. A paradigm shift has taken place to utilize tissue engineering and drug delivery approaches towards the regeneration of these structures. Several prototypes of DOC structures have been regenerated such as temporomandibular joint (TMJ) condyle, cranial sutures, tooth structures and periodontium components. However, many challenges remain when taking in consideration the high demand for esthetics of DOC structures, the complex environment and yet minimal scar formation in the oral cavity, and the need for accommodating multiple tissue phenotypes. This review highlights recent advances in the regeneration of DOC structures, including the tooth, periodontium, TMJ, cranial sutures and implant dentistry, with specific emphasis on controlled release of signaling cues for stem cells, biomaterial matrices and scaffolds, and integrated tissue engineering approaches.

Fig. 1

Drug delivery in dental, oral and craniofacial tissue engineering. Growth factors and other bioactive molecules may be delivered via in situ forming injectable matrices or pre-shaped implants for the regeneration of teeth, periodontium, cranial sutures, salivary glands, temporomandibular joints, and calvarial bone.

Fig. 2

Various forms of poly-lactic-co-glycolic acid (PLGA) based matrices and scaffolds for dental, oral and craniofacial tissue engineering. A. Porous PLGA sponge fabricated using salt-leaching techniques. B. PLGA microspheres encapsulating growth factors showing smooth spherical surface and wide range of diameters. C. PLGA nanofibers fabricated using electrospining techniques. D. PLGA microspheres in chitosan-based gels for advanced controlled delivery and cell interaction. A, B, C: scanning electron microscopy (SEM). D: phase contrast image.

Fig. 3

Engineered cranial suture implants. A. TGF-β3 loaded poly-lactic-co-glycolic acid (PLGA) microspheres (arrows) in gelatin sponge as a pre-sized engineered implant. B. Osteogenic healing of osteotomized region of the fused rat cranial suture after implantation of placebo loaded collagen sponge implants (4 weeks). C. Formation of a bone–fibrous tissue–bone interface and regulation of osteogenesis in the osteotomized region of the fused rat cranial suture after implantation of TGF-β3 treated engineered cranial suture implants (4 weeks). H&E stain. b: bone, f: fibrous tissue.

Fig. 4

Controlled release of TGF-β1 from poly-lactic-co-glycolic acid (PLGA) microspheres increases bone ingrowth into hollow titanium implants. A. Hollow titanium implants with 1 mm macropores were custom fabricated. To compare outcome to a rapid release system, 1 μg of TGFβ1 was also adsorbed to gelatin sponge carrier (D and E). After 4 weeks of implantation in rabbit humeri, delivery of TGF-β1 led to increases in bone-to-implant contact (BIC) and bone volume within 1 mm macropores (BV/TV) (B–E) as compared to placebo control spheres (F and G). Approximately 10 times more TGFβ1 was required for rapid release from gelatin sponge (D and E) to obtain comparable results to controlled release using PLGA microspheres (B and C). H&E stain. CB: cortical bone, Ti: titanium implant.