Regenerative medicine” emerged as a multidisciplinary field involving biology, medicine and engineering that is likely to revolutionize the ways we improve the health and quality of life for millions of people worldwide by restoring, maintaining or enhancing tissue and organ function (Ricci & Terracio, Int Dent J; 2011). The ultimate goal of regenerative therapy is to develop fully functional bioengineered organs which work in cooperation with surrounding tissues to replace organs with loss of function or severe damage due to disease, injury, aging or congenital defects. Dental medicine remains in the frontline of this fast progressing field dealing with the design and development of new materials that stimulate tissue regeneration. The application of Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) has been established as a daily practice in dentistry, especially in periodontology and implantology.

 

More than five million dental implants are performed every year with an expected increase up to 12-15% in the coming years (Misch, Dental Implant Prosthetics; 2014). However, approximately 5-11% of dental implants fail within 10-15 years due to biological or mechanical factors such as peri-implantitis, degradation of structural materials and connections, implant design, bone density, surgical and prosthetic complications or patient specific conditions (Bijukumar et al, Curr Osteoporos Rep; 2018). Based on the principles of regenerative medicine and taking advantage of stem cells and growth factors, biomedical implants provide a promising solution for more effective osseointegration and increased resistance to a post-operative infection.

 

Stem cells are unspecialized cells capable of renewing themselves through cell division. Under certain conditions, they can be induced to become tissue- or organ-specific cells with special functions. Two primary sources of stem cells are naturally present in the human body: embryonic stem cells and adult or somatic stem cells. In 2006, researchers made another breakthrough by identifying conditions that would allow specialized somatic cells to be “reprogrammed” genetically assuming a stem cell-like state (Takahashi & Yamanaka, Cell; 2006). The oral area is a rich source of stem cells, and it is therefore important for dental clinicians and researchers to further characterize these cells aiming to develop new and effective strategies for dental applications (Egusa et al, J Prosthodont Res; 2012).

 

Growth factors are evolutionary-conserved, relatively small and stable polypeptides that regulate a variety of cellular behaviors including growth, migration, differentiation, apoptosis and survival, in both positive and negative manners (Mina, Stem Cell Biology & Tissue Engineering in Dental Sciences; 2015). They also play an important role in the maintenance of tissue homeostasis and wound healing in the adult. Both in vitro and in vivo studies demonstrated that specific growth factors modify reputed elements of periodontal wound healing, thus achieving significant periodontal regeneration in animals (Lecanda et al, J Cell Biochem; 1997). Particularly, they exert effects on soft tissue components of the periodontium such as the periodontal ligament and the gingival connective tissue, as well as on the hard tissue structures such as the alveolar bone and the cementum.

 

Stem cells have the potential to regenerate bone using tissue-engineered scaffold with specific growth factors. Several studies have reported the successful application of this strategy in dental implantation as it significantly improved bone formation and presented adequate weight and height of the bone for implant placement (Bijukumar et al, Curr Osteoporos Rep; 2018). In 2009, a fully functioning tooth replacement was achieved by transplantation of a bioengineered tooth germ into the alveolar bone of a lost tooth region in an adult mouse, underlining the real potential for bioengineered mature organ replacement as a next generation regenerative therapy (Ikeda et al, PNAS; 2009).

Through the development of strong bonds and a close cooperation with scientific institutions, WAGro promotes biomedical research and innovation in the field of regenerative dental medicine. Advanced protocols and techniques based on the use of autologous materials are performed by specialists towards the improvement of clinical practice with respect to patients’ benefit.

 

 “IPG” DET protocol: a pioneer technique of internal bone regeneration in the sinus without the need of sinus floor elevation

 

Patients suffering from alveolar ridge deficiencies are treated with extensive bone transplantation or sinus floor elevation (SFE) procedures in order to accomplish a successful and stable dental implantation. In 2014, “IPG” DET – called the Ioannis P. Georgakopoulos Dentist Education Institute Technique – has been proven a solid and reliable alternative to SFE (Georgakopoulos et al, JIACD; 2014; Georgakopoulos et al, Dentistry; 2016). “IPG” DET is a well-established and efficient dental implantation protocol that combines a complex of fibrin, concentrated growth factors and CD34+ stem cells (fibrin membrane) along with bone grafting and intentional perforation of the Schneider’s membrane towards a rapid implant insertion. The use of CD34+ stem cells from the same patient and the sinus membrane perforation present the main differences of “IPG DET” compared to all other techniques and methods of SFE. Sinus gains the ability to adapt to new conditions and form new bone bilaterally to implant. Fibrin membrane represents the first microenvironment for inducing tissue repair, behaving not only as a sealing matrix but also as scaffold for invading leukocytes and other cells involved in the tissue repair process. Blood components, incorporated in the fibrin membrane, act in an orchestrated way modulating the proliferative, inflammatory and immune responses of tissue repair. A massive research work has been conducted by specialists in the field of advanced dentistry for the improvement of the methods used to obtain fibrin membrane. As a result of these efforts, new medical blood centrifugation protocols have been developed and are now offered in dental clinical practice providing biomaterials of high quality, ready for use in tissue regeneration (Rodella et al, Microsc Res Tech; 2011; Oliveira et al, 2018).

 

Transforming a patient’s own tooth into autologous graft

The idea of transforming a patient’s own tooth into autologous grafting materials receives considerable attention from dentists worldwide and is recognized as the novel “gold standard” of dental grafts. Common graft materials are only osteoconductive (the bone graft material serves as a scaffold for new bone growth in the presence of native bone). Similar to the autologous bone, tooth is not only osteoconductive but also osteoinductive, promoting new bone formation from progenitor multipotent cells that are influenced by several factors to differentiate into functional osteoblasts. Promiscuous protocols have been developed to provide dentists with such autologous grafts of high quality (Bono et al, J Appl Biomater Funct Mater; 2017). Osteoinduction is possible because the demineralization process releases many bone’s and blood vessels’ growth factors, such as BMP-2 that promotes mesenchymal stem cells’ differentiation into osteoblasts or chondrocytes. Furthermore, such protocols ensure the wettability of the graft that determines the biological cascade of events at the biomaterial/host interface. Graft surface composition and hydrophilicity are parameters that play an important role in implant–tissue interaction and osseointegration.