1
CHAPTER 1
The Temporomandibular Joint
Table 1.1: Table of Abbreviations
APC Antigen presenting cells MHC Major histocompatibility complex
ASTM American Society for Testing and
Materials
MEM Minimum essential medium
bFGF Basic fibroblast growth factor MMP Matrix metalloproteinases
BMP-2 Bone morphogenetic protein-2 PCL Polycaprolactone
CAD Computer assisted design
PDGF Platelet derived growth factor
CC Costal chondrocytes PGA Polyglycolic acid
CT Computerized tomography PLA/PGA Polylactic acid/polyglycolic acid
DF Dermal fibroblast PLGA Poly(lactic-co-glycolic acid)
EB
Embryoid body PLLA Poly-L-lactic-acid
ECM Extracellular matrix
PMMA Polymethylmethacrylate
ELISA Enzyme-linked
immunosorbent assay
RT Reverse transcription
ePTFE Expanded
polytetrafluoroethylene
rt-PCR Real-time polymerase chain reaction
FDA Food and Drug
Administration
SDS Sodium dodecyl sulfate
Fos-LI Fos-like immunoreactivity SEM Scanning electron microscopy
G-HCl Guanidine hydrochloride SLS Selective laser sintering
GAG Glycosaminoglycan TGF-β1, β3 Transforming growth factor-β1, β3
H&E Hematoxylin and eosin
TMB 3,3’,5,5’-Tetramethylbenzidine
HBSS Hanks’ balanced salt solution TMD
Temporomandibular disorder
hESC Human embryonic stem cell TMJ
Temporomandibular joint
IGF-1 Insulin-like growth factor-1 TNF Tissue necrosis factor
IL-1,2 Interleukin-1, 2 UHMWPE Ultra-high molecular weight
polyethylene
1.1 TISSUE ENGINEERING
The lack of an intrinsic regenerative ability in cartilaginous tissues renders them ideal candidates for
tissue engineering approaches.The field of musculoskeletal tissue engineering focuses on producing
tissue replacements with suitable biomechanical and structural properties through the use of natural
and synthetic materials. In general, tissue engineering approaches utilize the interaction of cells,
scaffolds, biological signals, and bioreactors.
The choice of cell source is fundamental in the tissue engineering process. A clinically feasible
cell source should be abundant, healthy, and leave little donor site morbidity [1]. Selection of an
2 CHAPTER 1. THE TEMPOROMANDIBULAR JOINT
alternative source must also consider the functionality of the cells. A myriad of cell sources can be
used for cartilaginous tissue engineering, such as native cartilage cells from the autologous site, or
cartilage cells from a different joint. Further, mesenchymal stem cells from different sources, such as
bone marrow, fat, muscle, or periodontal tissues, could be differentiated to cartilage.
The type of scaffolding used will have a profound impact on outcomes. Hydrogels have proven
to be the scaffolding choice in numerous tissue engineering applications. Alginate and agarose hy-
drogels are two popular natural hydrogels used in cartilage tissue engineering. Non-woven meshes of
synthetic polymers have also seen success in cartilage tissue engineering. A popular choice, polygly-
colic acid (PGA), has seen encouraging results for cartilage tissue engineering [2]–[4]. A scaffoldless
approach has also been proposed, where cartilage cells self-assemble in a mold to produce cartilage
tissue analogues in vitro [5].
Biological signals can activate pathways that cascade into extracellular matrix (ECM) protein
production to recapitulate the native tissues [6]. Growth factors are the most common biological
signals utilized in tissue engineering; however, chemicals such as ascorbic acid, proline, and glu-
tamine can also serve as signals. Further, genetic engineering can be used to express these and other
therapeutic agents within the cells.
Mechanical force may also be applied during the culturing process to produce a phenotypically
correct tissue with proper extracellular matrix alignment, which is often obtained through the use of
bioreactors. Four main types of forces are currently used in cartilage-culturing processes: hydrostatic
pressure, direct compression, “high-shear” fluid environments, and low-shear” fluid environments.
Specifically, for the temporomandibular joint (TMJ), tissue engineering investigations of its
two major structures (the disc and the condyle) have been conducted independent of one another.
Both the condyle and disc tissue-engineering communities have made significant advances in recent
years, although the investigations on the disc began much earlier. Four TMJ disc tissue engineering
studies were published from 1991 to 2001 [7]–[10], and while important issues were addressed, such
as cell source, biomaterials, and shape specific scaffolds, the common theme among these pioneering
studies was an unfamiliarity with the available characterization data for the TMJ disc in terms of
cell content and matrix composition.
In 2001, strategies for TMJ tissue engineering, including cell sources, scaffolding materials,
and signaling, were reviewed [11], and a photopolymerization method for developing a shape-
specific TMJ disc scaffold was developed [12, 13]. Although, it was not until three years later that
the next effort of TMJ disc tissue-engineering studies were published, all of which utilized cells
derived from the TMJ disc. Most of these studies were from Athanasiou’s group, which collectively
supported the use of PGA non-woven meshes over agarose gels [2], while promoting the spinner
flask as the preferred seeding method with PGA scaffolds. They also demonstrated the importance
of using growth factors such as insulin-like growth factor-I [14, 15],and recommended 25 μg/mL as
a preferred ascorbic acid concentration [16]. Athanasious group also revealed the detrimental effects
of passaging and pellet culture [17], and investigated the effects of hydrostatic pressure [18] and
rotating wall bioreactors [19]. In 2006, another study suggested the use of platelet derived growth

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