**6. Tissue engineering**

In recent past years, detailed and exhaustive reviews have been published covering all the relevant data about the experimental [75], technical aspects, and indications of tissue engineering in TMJ [76–81]. Therefore, this section only summarizes the most relevant aspects of tissue engineering of TMJ using minimally invasive techniques. In the last two decades, new studies have contributed to understand what are the appropriate scaffolds, cells and biological for TMJ diseases, and all these advancements are based on the perfectly known structures of the different joint constituents.

Traditionally, the principal elements of tissue engineering-based regenerative strategies are scaffolds, cells, and biological stimuli. Those used in TMJ are summarized in **Table 1**. Although through invasive methods all strategies are possible to regenerate TMJ components when minimally invasive techniques are used, two methods are possible in cartilage and bone engineering: *in situ* tissue engineering incorporating an acellular scaffold matrix that attract and fix local cells thus guiding the process of regeneration and *ex vivo* cell seeding on the scaffold that initiates and regulates the regenerative mechanisms [101]. On the other hand, to induce more rapid ECM synthesis, scaffolds can be embedded with growth factors. Also,


**Table 1.** 

*Scaffolds and cells used in TMJ tissue engineering.* 

intraarticular injection of cells or local delivery of biologically active molecules can be a strategy, but these cannot be regarded properly as tissue engineering.

Scaffolds serve as a supportive structure to the engineered tissues. As a rule, the used scaffolds must promote the differentiation of cells into chondrocytes and stimulate the synthesis of cartilaginous ECM. Both natural and synthetic scaffolds have been experimented for engineering the TMJ (**Table 1**). Nevertheless, the most suitable approach should be reconstructed for both full articulating surfaces by stabilizing scaffolds on the articular surfaces to be regenerated and autologous chondrocytes within the scaffold. But in the case of TMJ, the reconstruction of the disc is also important. Nevertheless, as the replacement of the articular disc does not seem to be feasible at the current state of tissue engineering, lining the articular fossa with resistant engineered cartilage tissue would be an alternative in patients after discectomy [78].

Diverse cells have been used in TMJ tissue engineering (see **Table 1**) within different scaffolds. The local delivery of mesenchymal stem cells (MSCs) within TMJ has proved to have beneficial effects on TMJ degenerative diseases [79]. Furthermore, another strategy would be stimulating the resident mesenchymal stem cells present in the synovial layer [102] and synovial fluid of TMJ [103]. MSCs are able to secrete bioactive molecules, such as growth factors, cytokines, and chemokines, which exert their biological role under injury conditions [104].

Growth factors help tissue regeneration promoting the differentiation and proliferation of cells and supporting ECM synthesis and specialization. Thus, the incorporation of growth factors to the scaffolds, the direct intraarticular delivery of growth factors, or stimulating the exogenous or resident cells to secrete and release growth factor can result in an improvement of tissue regeneration. Various technologies for incorporation of growth factors into scaffolds are possible. At present, the three key growth factors for TMJ regeneration are bFGF, IGF-1, and TGF-β1 [105]. However, fibrochondrocytes from mandibular condyle are less responsive to IGF-1 than hyaline chondrocytes [86]. TGF-β1 stimlates cell proliferation, and on the production of ECM in TMJ disc implants [106], and TGF-β1 and IGF-1 acting together promote cellular proliferation and secretion of type I collagen and glycosaminoglycans [107]. In culture, bFGF increased the proliferation of fibrochondrocytes from mandibular condyle more than TGF-β1 and IGF-1 [108]. Finally, PDGF significantly increases the proliferation rate of the TMJ-disc-derived cells, collagen, and hyaluronic acid synthesis in engineered TMJ disc [109].

Another source of bioactive molecules to be delivered into TMJ is the MSCconditioned medium collectively known as the MSC secretome. It contains trophic factors and various MSC-based clinical trials that have revealed that transplanted MSCs exert their biological functions through trophic modulations rather than differentiation potential [110]. Similar properties have the secretome of the periodontal ligament-derived MSCs [111]. Finally, exosomes, cell-secreted nano-sized vesicles covered by the bilipid membrane, containing a myriad of regulatory components including microRNAs (miRNAs), mRNAs, and proteins [112], could be in the future a reliable possibility to stimulate TMJ regeneration.

*Nonsurgical Strategies for the Treatment of Temporomandibular Joint Disorders DOI: http://dx.doi.org/10.5772/intechopen.85186* 
