Research - Theravex

About

Research and development

Since 2004, our research team at Biointelligent Technology Systems has been immersed in exploring the possibilities of bone tissue regeneration. This scientific journey has encompassed multiple areas of study, from biomaterials to stem cells, culminating in discoveries that promise to revolutionize the treatment of bone defects and pathologies.

In the early stages of our research, we focused on studying a variety of biomaterials, growth factors, and proteins, with the aim of understanding how these components influenced bone tissue regeneration. During these initial years, we conducted numerous studies to identify the most effective materials and factors.

Subsequently, our attention turned to the use of stem cells in regenerative medicine, opening new avenues of research and demonstrating the potential of stem cells in this field. As we delved deeper, we investigated the use of different types of stem cells to promote tissue regeneration.

A crucial milestone in our research was the discovery of a pluripotent stem cell in the dental pulp of wisdom teeth, which we named DPPSC (Dental Pulp Pluripotent Stem Cells). These cells exhibited unique characteristics and remarkable genetic stability, making them a promising tool for tissue regeneration. Following this discovery, we identified the key genes and proteins responsible for tissue regeneration.

Thanks to these discoveries, we managed to understand various cellular signaling pathways during the regeneration process. This knowledge was fundamental in developing new strategies and technologies in regenerative medicine.

The culmination of years of research in the field of stem cells and bone regeneration led to our innovative technology: BBL Technologies. This technology is based on creating an ideal environment for attracting stem or progenitor cells to the damaged area, enhancing cellular communication to achieve optimal regeneration of the affected tissue. BBL Technologies offers novel solutions for treating tissue defects or damage.

Since 2004, our team at Biointelligent Technology Systems has made significant strides in the study of tissue regeneration. Our findings have not only expanded scientific knowledge in this field but have also led to innovative technologies with the potential to transform regenerative medicine. We remain committed to researching and developing new solutions that improve the quality of life for people affected by tissue defects and pathologies.

BBL TECHNOLOGY

Bone Bioactive Liquid (BBL) is a specialized bioactive solution formulated with a saline base containing Calcium Chloride (CaCl2) and Magnesium Chloride (MgCl2-6H2O). This solution possesses a net negative charge, which optimally facilitates the attraction of progenitor cells towards the site of injury. This targeted recruitment of progenitor cells enhances cellular communication between these progenitor cells and adult tissue, thereby accelerating the process of wound healing and promoting a more coordinated regeneration of the injured area.

The formulation of BBL acts upon the calcium cascade, a critical pathway involved in cellular signaling and tissue remodeling. By modulating this cascade, BBL enhances the bioavailability of calcium ions at the site of injury, crucial for the activation of various cellular processes essential for tissue repair and regeneration.

Moreover, BBL also exerts regulatory effects on the postoperative inflammatory process. By mitigating excessive inflammation, BBL helps maintain a favorable environment for tissue repair and prevents complications that may arise from prolonged inflammatory responses.

In summary, Bone Bioactive Liquid (BBL) represents a sophisticated approach to enhancing tissue healing by leveraging its bioactive components to attract progenitor cells, modulate the calcium cascade, and regulate the inflammatory response, thereby promoting efficient and effective recovery post-injury or surgery.

OUR REPELLENT PUBLICATIONS

Type 1 Diabetes Treatments Based on Stem Cells.

Arana M, Kumar A, Ashwathnarayan A, Atari M, Barajas M.Curr Diabetes Rev. 2018;14(1):14-23.

Clinical Application of Umbilical Cord Mesenchymal Stem Cells Preserves β-cells in Type 1 Diabetes.

Al Madhoun A, Koti L, Carrió N, Atari M, Al-Mulla F.Stem Cells Transl Med. 2024 Feb 14;13(2):101-106.

Dental Pulp Stem Cells Derived From Adult Human Third Molar Tooth: A Brief Review.

Al Madhoun A, Sindhu S, Haddad D, Atari M, Ahmad R, Al-Mulla F.Front Cell Dev Biol. 2021 Oct 12;9:717624. doi: 10.3389/fcell.2021.717624. eCollection 2021.PMID: 34712658

The Effect of Commercially Available Endodontic Cements and Biomaterials on Osteogenic Differentiation of Dental Pulp Pluripotent-Like Stem Cells.

Maher A, Núñez-Toldrà R, Carrio N, Ferres-Padro E, Ali H, Montori S, Al Madhoun A.Dent J (Basel). 2018 Sep 22;6(4):48. doi: 10.3390/dj6040048.PMID: 30248979

CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy.

Roa-Mansergas X, Fadó R, Atari M, Mir JF, Muley H, Serra D, Casals N.Sci Rep. 2018 May 3;8(1):6997. doi: 10.1038/s41598-018-25485-7.PMID: 29725060

Chemically Defined Conditions Mediate an Efficient Induction of Dental Pulp Pluripotent-Like Stem Cells into Hepatocyte-Like Cells.

Gil-Recio C, Montori S, Al Demour S, Ababneh MA, Ferrés-Padró E, Marti C, Ferrés-Amat E, Barajas M, Al Madhoun A, Atari M.Stem Cells Int. 2021 Nov 8;2021:5212852. doi: 10.1155/2021/5212852. eCollection 2021.

Human dental pulp pluripotent-like stem cells promote wound healing and muscle regeneration.

Martínez-Sarrà E, Montori S, Gil-Recio C, Núñez-Toldrà R, Costamagna D, Rotini A, Atari M, Luttun A, Sampaolesi M.Stem Cell Res Ther. 2017 Jul 27;8(1):175. doi: 10.1186/s13287-017-0621-3.PMID: 28750661

Pancreatic differentiation of Pdx1-GFP reporter mouse induced pluripotent stem cells.

Porciuncula A, Kumar A, Rodriguez S, Atari M, Araña M, Martin F, Soria B, Prosper F, Verfaillie C, Barajas M.Differentiation. 2016 Dec;92(5):249-256.

Improvement of osteogenesis in dental pulp pluripotent-like stem cells by oligopeptide-modified poly(β-amino ester)s.

Núñez-Toldrà R, Dosta P, Montori S, Ramos V, Atari M, Borrós S.Acta Biomater. 2017 Apr 15;53:152-164. doi: 10.1016/j.

Comparison of 0.12% Chlorhexidine and a New Bone Bioactive Liquid, BBL, in Mouthwash for Oral Wound Healing: A Randomized, Double Blind Clinical Human Trial.

Ferrés-Amat E, Al Madhoun A, Ferrés-Amat E, Carrió N, Barajas M, Al-Madhoun AS, Ferrés-Padró E, Marti C, Atari M.J Pers Med. 2022 Oct 16;12(10):1725.

S53P4 Bioactive Glass Inorganic Ions for Vascularized Bone Tissue Engineering by Dental Pulp Pluripotent-Like Stem Cell Cocultures.

Núñez-Toldrà R, Montori S, Bosch B, Hupa L, Atari M, Miettinen S.Tissue Eng Part A. 2019 Sep;25(17-18):1213-1224.

Chemically Defined Conditions Mediate an Efficient Induction of Mesodermal Lineage from Human Umbilical Cord- and Bone Marrow- Mesenchymal Stem Cells and Dental Pulp Pluripotent-Like Stem Cells.

Al Madhoun A, Alkandari S, Ali H, Carrio N, Atari M, Bitar MS, Al-Mulla F.Cell Reprogram. 2018 Feb;20(1):9-16.

Histologic and Histomorphometric Evaluation of a New Bioactive Liquid BBL on Implant Surface: A Preclinical Study in Foxhound Dogs.

Ferrés-Amat E, Al Madhoun A, Ferrés-Amat E, Al Demour S, Ababneh MA, Ferrés-Padró E, Marti C, Carrio N, Barajas M, Atari M.Materials (Basel). 2021 Oct 19;14(20):6217. d

Dental pulp of the third molar: a new source of pluripotent-like stem cells.

Atari M, Gil-Recio C, Fabregat M, García-Fernández D, Barajas M, Carrasco MA, Jung HS, Alfaro FH, Casals N, Prosper F, Ferrés-Padró E, Giner L.J Cell Sci. 2012 Jul 15;125(Pt 14):3343-56.

Dental pulp pluripotent-like stem cells (DPPSC), a new stem cell population with chromosomal stability and osteogenic capacity for biomaterials evaluation.

Núñez-Toldrà R, Martínez-Sarrà E, Gil-Recio C, Carrasco MÁ, Al Madhoun A, Montori S, Atari M.BMC Cell Biol. 2017 Apr 21;18(1):21.

Comparative Proteomic Analysis Identifies EphA2 as a Specific Cell Surface Marker for Wharton’s Jelly-Derived Mesenchymal Stem Cells.

Al Madhoun A, Marafie SK, Haddad D, Melhem M, Abu-Farha M, Ali H, Sindhu S, Atari M, Al-Mulla F.Int J Mol Sci. 2020 Sep 3;21(17):6437.

Defined three-dimensional culture conditions mediate efficient induction of definitive endoderm lineage from human umbilical cord Wharton’s jelly mesenchymal stem cells.

Al Madhoun A, Ali H, AlKandari S, Atizado VL, Akhter N, Al-Mulla F, Atari M.Stem Cell Res Ther. 2016 Nov 16;7(1):165. doi: 10.1186/s13287-016-0426-9.PMID: 27852316

Ferrés-Amat E, Pastor-Vera T, Rodriguez-Alessi P, Ferrés-Amat E, Mareque-Bueno J, Ferrés-Padró E. The prevalence of ankyloglossia in 302 newborns with breastfeeding problems and sucking difficulties in Barcelona. Eur J Paed Dent. 2017;18: 319-325.

Caicedo-Rubio M, Ferrés-Amat E, Ferrés-Padró E. Implant-supported fixed
prostheses in a Patient with Osteogenesis Imperfecta: A 4-year follow-up. J Clin Exp Dent. 2017;9:e1482-1486.

Ferrés-Amat E, Pastor-Vera T, Rodriguez-Alessi P, Ferrés-Amat E, Mareque-Bueno J, Ferrés-Padró E. Management of ankyloglossia and breastreeding difficulties in the newborn: Breastfeeding sessions, Myofunctional therapy and Frenotomy. Case Rep Pediatr 2016;2016:3010594

Ferrés-Amat E, Pastor-Vera T, Ferrés-Amat E, Mareque-Bueno J, Prats-
Armengol J, Ferrés-Padró E. Multidisciplinary management of ankyloglossia in childhood. Treatment of 101 cases. A protocol. Med Oral Patol Oral Cir Bucal 2016;21:e39-47.

Ferrés-Amat E, Prats-Armengol J, Maura-Solivellas I, Ferrés-Amat E, Mareque-Bueno J, Ferrés-Padró E. Gingival bleeding of a high-flow mandibular arteriovenous malformation in a child: case report with 8-year
follow-up. Case Rep Pediatr