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Injectable Bone for Regeneration with Mesenchymal Stem Cells and Platelet-Rich Plasma - HOW IT WORKS

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Platelet-rich plasma for regeneration of neural feedback pathways around dental implants

OUR CLINICAL STUDY

MAINTAINENCE OF DENTAL IMPLANT INTEGRITY IN CHEMOTHERAPY TREATED PATIENTS; A BASIC AND CLINICAL STUDY
Victor P Terranova  DMD, MS, PhD; David Salomon Phd, Steven Cisternas DDS;Bay Street Stem Cell Science

Dental implant failure is common in patients receiving systemic chemotherapy or localized craniofacial radiotherapy. Little is known about the survival rate of bone derived mesenchymal stem cells during and after chemotherapeutic administration. Attempts to maintain implant integrity during and post cancer treatment are therefore needed. Protocols to design appropriate implant environments that can maintain integrity and survive therapy are almost nonexistent. Bone resorption around the tooth socket is the primary reason for dental implant failure during and after cancer therapy. Ectopic bone formation by demineralized bone matrix in ectopic in vivo sites is a well-known fact. Bioactivity of the demineralized bone matrix is due in large part to the bioactivity of the growth factor bone morphogenetic protein 2 BMP-2. Recombinant and bioactive and GMP tested BMP-2 that has been successfully used in orthopedic settings for bone fracture repair is commercially available.Generation of artificial organs has been achieved using embryonic stem (ES) cells or induced pluripotent stem (IpS) cells . However, teratoma formation has limited the clinical use this technology using these cellular components.Autologous mesenchymal stem cells (MSCs) obtained from either the bone marrow (BMSCs) as well as autologous dental pulp stem cells (DPSCs) from deciduous teeth can be readily obtained and cultured briefly in vitro. In this setting, these MSCs can be treated with sources of recombinant growth factors and appropriate scaffolding matrices such as macro porous biphasic calcium phosphate and hyaluronic acid (HA). To develop fully functional dental implants in patients who are under chemo- or radio-therapeutic stress, we propose to use autologous DPSCs cells that have been briefly cultured in vitro in the presence of autologous platelet rich-plasma (PRP) or platelet-rich fibrin supplemented with recombinant BMP-2 (4ng/ml) which will facilitate their differentiation into osteoblasts, ameloblasts and periodontal ligament cells. After 4 days these primed cells with be mixed with macroporous biphasic calcium phosphate and HA and transplanted into the cleared dental sockets of patients who are currently on or have recently received and stopped chemo- or radio-therapy.Additionally, there are few clinical studies that address the osteogenesis and subsequent osseointegration around dental implants in active chemotherapy treated patients. We have found no studies that examine radiotherapy patients and dental implant integration and survival. Chemotherapy treatment regimes vary greatly depending on the specific tumor bourdon, time of cellular transformation, origin and type of tumor, grade and location, systemic factors compromising the patient, environmental factors compromising the patient, current patient medications, and genetic factors. Common chemotherapy, which is the mainstay of oncology includes, but is not limited to, cis- or carboplatin, 5-FU, tamoxifen, adriamycin, various monoclonial antibodies (rituximab, imbruvica, e.g.), velcade, and other tumor cell specific cell surface binding chemotherapeutic agents. All of these chemotherapeutic agents have adverse side effects that at the worst,  can include demise of the patient. Furthermore there is little known about the dental needs of the active chemotherapy patient. Studies are now ongoing to ascertain the survival rate on dental implants in the diabetic patient and the patient who smokes. We propose to evaluate the ability of dental implants to survive in selected chemotherapy treated patients and to devise a therapy for increased survival of dental implants in all chemotherapy treated patients based on the above mentioned preclinical trial studies. We hypothesize that dental implants can be made to survive in the chemotherapy treated patient by modulating the bone mesenchymal stem cell resistance.

To test this hypothesis we propose conducting the afore mentioned preclinical studies which will be run in parallel with clinical placement of Sweden & Martina Shelta SL Dental implants.

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