Copy to clipboard 
Novadip Biosciences recently received an infusion of €40 million (~USD $40 million) in investments, increasing its total funding to €88 million. The Belgium-based company will use the capital to develop a new class of adipose-derived stem cell (ASC) tissue regeneration platforms designed to accelerate bone union and healing through single-treatment cures. A Phase I/II clinical trial for NovaDip’s NVD-X3 in spine fusion and bone nonunion procedures is expected to begin in Europe by the end of 2022.
Denis Dufrane, M.D., Ph.D., CEO and Co-founder of Novadip, is a thought leader and entrepreneur in the biotechnology industry. He shared his thoughts on the company’s innovative tissue regeneration technology and said it could improve the standard of care in orthopedics for the treatment of critical bone defects, radius fractures and spine fusions.
What properties of ASCs make them foundations of regenerative medicine, and what clinical benefits do they provide in orthopedic applications?
Dr. Dufrane: These are the questions I attempted to answer at the Université Catholique de Louvain while conducting research focused on the reconstruction of large bone defects.
Bone healing requires two major properties. The first is the body’s ability to create new blood vessels and resist low oxygen tensions to regenerate tissue. In healthy tissue, oxygen tensions correspond to around 5%. In a bone defect, it’s below 1%. The second property is the formation of new bone.
When I started my research in 2007, bone marrow mesenchymal stem cells (MSCs) were the most suitable option to reconstruct defects because they are derived from bone tissue. I compared the efficacy of bone marrow MSCs with ASCs, which were a recent discovery at the time.
My team conducted in vivo and in vitro experiments of bone marrow MSCs and ASCs in very low oxygen tensions and published the results in the journal Biomaterials. Our results demonstrated the clear superiority of ASCs in resisting low oxygen tensions and recreating an optimal vascularization environment. That’s why we considered ASCs to be superior to bone marrow MSCs, which had been used in clinics for more than 50 years.
What is the critical stage of bone regeneration, and how do ASCs improve the process?
Dr. Dufrane: The osteogenic differentiation needed for fracture healing in bone marrow MSCs is limited compared to embryonic stem cells; therefore, my research team used adult stem cells to help construct large bones.
After age 50, people lose about 50% of the capacity to produce MSCs and the osteogenic differentiation necessary to produce new bone. That’s why fractures take longer to heal in older individuals.
My research published in the journal Cell Transplantation showed that a patient’s age has no impact on the properties of ASCs. They clearly provided clinical benefits and were the superior choice for most patients, regardless of their age.
Obtaining ASCs from fatty adipose tissue is also significantly faster and easier than from bone marrow.
Why is congenital pseudarthrosis of the tibia (CPT) so difficult to treat, and how does stimulating bone formation improve on current approaches?
Dr. Dufrane: The autologous bone product that we derived from ASCs was realized and developed to cure large bone defects found in adult trauma patients. Large bone defects also occur in pediatric patients who suffer from CPT, a rare genetic disease associated with neurofibromatosis type 1, the spontaneous bowing of the tibia and increased fracture risk.
Nonunion fractures in these patients typically occur due to a lack of bone formation. CPT limits the body’s capacity to develop new bone and destroys existing bone. This imbalance creates significantly larger bone defects and high bone resorption, often resulting in amputations.
Our technology demonstrates that ASCs promote healthy and durable bone formation and inhibit bone resorption, thereby treating normal physiology. This discovery has the potential to save limbs and restore mobility in these patients with a single treatment. Surgery is the current standard of care for CPT. Still the autologous bone graft products used during procedures don’t treat the pathophysiology of the disease and lead to poor long-term outcomes.
Pseudarthrosis following spinal fusion is a significant clinical issue, especially as annual case volumes eclipse 600,000. How is your company addressing it?
Dr. Dufrane: We’ve developed a novel allogenic matrix product that delivers growth factors and microRNAs needed to accelerate tissue healing and repair bone defects. BMP-2 growth factors are the only products on the market with clinical data to support their use in spine fusions. However, they are used only in single-level fusions to limit the risk of side effects.
Our product can be used in multi-level spine fusions, tumor resections and scoliosis treatment. The allogenic matrix provides a tight, controlled release of the drug to accelerate tissue healing and avoid the side effects associated with BMP-2 growth factors.
The matrix is an “off-the-shelf” bioactive powder described as having superior intraoperative handling characteristics. Why are these features important from the provider’s perspective?
Dr. Dufrane: Our product is unique because key growth factors and microRNA are synthesized by the cell in the matrix, meaning it can be stored at room temperature and readily available to surgeons. Alternatively, allogenic products must be cryopreserved before use.
I’m still a practicing orthopedic surgeon and understand the importance of good intraoperative handling. The matrix is synthesized by the patient’s own cells, so it can be reconstituted with physiological solutions like blood and bone marrow and placed in any type of bone defect. It’s a single formulation for universal applications.
What must companies and regulators do to maintain patient safety as more ASC products come to market?
Dr. Dufrane: This is an important topic. The bone market is fragmented into synthetics of cell viable products, growth factors and bone matrix derived from tissue. Most of these drugs have not demonstrated effectiveness in clinical trials, which are required to establish the safety and efficacy of biologics dosing.
Currently, bone substitute products cannot claim a dose articulation, therefore increasing the risks of side effects or a lack of efficacy. We’re attempting to show the efficacy of our product through clinical trials. This could be a significant disruption in how these products are developed. I believe the plasticity of our platform will allow it to be used for treating not only bone defects, but also for cartilage, tendon and muscle applications.
Novadip Biosciences recently received an infusion of €40 million (~USD $40 million) in investments, increasing its total funding to €88 million. The Belgium-based company will use the capital to develop a new class of adipose-derived stem cell (ASC) tissue regeneration platforms designed to accelerate bone union and healing through...
Novadip Biosciences recently received an infusion of €40 million (~USD $40 million) in investments, increasing its total funding to €88 million. The Belgium-based company will use the capital to develop a new class of adipose-derived stem cell (ASC) tissue regeneration platforms designed to accelerate bone union and healing through single-treatment cures. A Phase I/II clinical trial for NovaDip’s NVD-X3 in spine fusion and bone nonunion procedures is expected to begin in Europe by the end of 2022.
Denis Dufrane, M.D., Ph.D., CEO and Co-founder of Novadip, is a thought leader and entrepreneur in the biotechnology industry. He shared his thoughts on the company’s innovative tissue regeneration technology and said it could improve the standard of care in orthopedics for the treatment of critical bone defects, radius fractures and spine fusions.
What properties of ASCs make them foundations of regenerative medicine, and what clinical benefits do they provide in orthopedic applications?
Dr. Dufrane: These are the questions I attempted to answer at the Université Catholique de Louvain while conducting research focused on the reconstruction of large bone defects.
Bone healing requires two major properties. The first is the body’s ability to create new blood vessels and resist low oxygen tensions to regenerate tissue. In healthy tissue, oxygen tensions correspond to around 5%. In a bone defect, it’s below 1%. The second property is the formation of new bone.
When I started my research in 2007, bone marrow mesenchymal stem cells (MSCs) were the most suitable option to reconstruct defects because they are derived from bone tissue. I compared the efficacy of bone marrow MSCs with ASCs, which were a recent discovery at the time.
My team conducted in vivo and in vitro experiments of bone marrow MSCs and ASCs in very low oxygen tensions and published the results in the journal Biomaterials. Our results demonstrated the clear superiority of ASCs in resisting low oxygen tensions and recreating an optimal vascularization environment. That’s why we considered ASCs to be superior to bone marrow MSCs, which had been used in clinics for more than 50 years.
What is the critical stage of bone regeneration, and how do ASCs improve the process?
Dr. Dufrane: The osteogenic differentiation needed for fracture healing in bone marrow MSCs is limited compared to embryonic stem cells; therefore, my research team used adult stem cells to help construct large bones.
After age 50, people lose about 50% of the capacity to produce MSCs and the osteogenic differentiation necessary to produce new bone. That’s why fractures take longer to heal in older individuals.
My research published in the journal Cell Transplantation showed that a patient’s age has no impact on the properties of ASCs. They clearly provided clinical benefits and were the superior choice for most patients, regardless of their age.
Obtaining ASCs from fatty adipose tissue is also significantly faster and easier than from bone marrow.
Why is congenital pseudarthrosis of the tibia (CPT) so difficult to treat, and how does stimulating bone formation improve on current approaches?
Dr. Dufrane: The autologous bone product that we derived from ASCs was realized and developed to cure large bone defects found in adult trauma patients. Large bone defects also occur in pediatric patients who suffer from CPT, a rare genetic disease associated with neurofibromatosis type 1, the spontaneous bowing of the tibia and increased fracture risk.
Nonunion fractures in these patients typically occur due to a lack of bone formation. CPT limits the body’s capacity to develop new bone and destroys existing bone. This imbalance creates significantly larger bone defects and high bone resorption, often resulting in amputations.
Our technology demonstrates that ASCs promote healthy and durable bone formation and inhibit bone resorption, thereby treating normal physiology. This discovery has the potential to save limbs and restore mobility in these patients with a single treatment. Surgery is the current standard of care for CPT. Still the autologous bone graft products used during procedures don’t treat the pathophysiology of the disease and lead to poor long-term outcomes.
Pseudarthrosis following spinal fusion is a significant clinical issue, especially as annual case volumes eclipse 600,000. How is your company addressing it?
Dr. Dufrane: We’ve developed a novel allogenic matrix product that delivers growth factors and microRNAs needed to accelerate tissue healing and repair bone defects. BMP-2 growth factors are the only products on the market with clinical data to support their use in spine fusions. However, they are used only in single-level fusions to limit the risk of side effects.
Our product can be used in multi-level spine fusions, tumor resections and scoliosis treatment. The allogenic matrix provides a tight, controlled release of the drug to accelerate tissue healing and avoid the side effects associated with BMP-2 growth factors.
The matrix is an “off-the-shelf” bioactive powder described as having superior intraoperative handling characteristics. Why are these features important from the provider’s perspective?
Dr. Dufrane: Our product is unique because key growth factors and microRNA are synthesized by the cell in the matrix, meaning it can be stored at room temperature and readily available to surgeons. Alternatively, allogenic products must be cryopreserved before use.
I’m still a practicing orthopedic surgeon and understand the importance of good intraoperative handling. The matrix is synthesized by the patient’s own cells, so it can be reconstituted with physiological solutions like blood and bone marrow and placed in any type of bone defect. It’s a single formulation for universal applications.
What must companies and regulators do to maintain patient safety as more ASC products come to market?
Dr. Dufrane: This is an important topic. The bone market is fragmented into synthetics of cell viable products, growth factors and bone matrix derived from tissue. Most of these drugs have not demonstrated effectiveness in clinical trials, which are required to establish the safety and efficacy of biologics dosing.
Currently, bone substitute products cannot claim a dose articulation, therefore increasing the risks of side effects or a lack of efficacy. We’re attempting to show the efficacy of our product through clinical trials. This could be a significant disruption in how these products are developed. I believe the plasticity of our platform will allow it to be used for treating not only bone defects, but also for cartilage, tendon and muscle applications.
You’ve reached your limit.
We’re glad you’re finding value in our content — and we’d love for you to keep going.
Subscribe now for unlimited access to orthopedic business intelligence.
DC
Dan Cook is a senior editor with more than 18 years of experience in medical publishing and an extensive background in covering orthopedics and outpatient surgery. He joined ORTHOWORLD to develop content focused on important industry trends, top thought leaders and innovative technologies.
