Summary
NVD003 is a new bone substitute made from the patient’s own fat-derived cells. Preclinical studies in animals and a first-in-human phase I clinical study have shown that it promotes bone repair while being well tolerated. These early results are encouraging, but larger trials are needed to confirm its efficacy and safety.
Why did we undertake this study?
Large bone defects or fractures that fail to heal properly (known as non-unions or pseudarthroses) remain a major challenge in orthopedic surgery. The current standard treatment bone autografting, which consists of harvesting a bone fragment from the patient has clear limitations: limited quantity of bones available, the harvesting procedure is painful, and complications may occur at the donor site. Although synthetic bone substitutes exist, they often lack the biological components necessary to stimulate true bone regeneration, especially in patients with poor bone healing conditions.
The aim of this study was therefore to evaluate a new type of autologous bone substitute, called NVD003, produced from the patient’s own fat-derived cells. This living implant contains viable osteogenic cells and mineral particles designed to promote bone formation and integration while avoiding donor-site complications.
What is the specific question(s) we wanted to answer?
We wanted to determine whether NVD003 is both safe and effective for bone regeneration in situations where natural bone healing is compromised.
Specifically, our objectives were:
- To assess whether the presence of viable cells in NVD003 is essential for its bone-forming activity.
- To verify if NVD003 can induce bone healing in preclinical models of critical-size bone defects.
- To evaluate, in a first group of patients with non-union fractures and in a small compassionate-use pediatric cohort, whether NVD003 promotes bone consolidation without adverse effects.
- To document long-term safety and the persistence of the regenerated bone over several years.
What did we find?
Preclinical results showed that NVD003 stimulated the expression of osteogenic markers and induced bone formation in animals. This effect was strictly dependent on the presence of living cells: the acellular version of the implant did not lead to new bone formation.
In the clinical study, nine adult patients with long-standing non-unions were treated with NVD003. Eight of them achieved full bone consolidation within 3 to 12 months. None experienced any adverse reactions linked to the product, and no late complications were observed up to 5 years after implantation.
In the compassionate-use pediatric cases (four children with congenital pseudarthrosis of the tibia), all patients also achieved complete and lasting bone healing.
Overall, NVD003 proved to be an easy-to-use bone graft substitute that integrates well with surrounding bone tissue and remains stable over time without signs of resorption or inflammation.
What are the implications of our findings?
These findings suggest that NVD003 could represent a promising alternative to traditional bone grafts, particularly in patients with poor bone healing capacity or in complex reconstructive surgeries. The absence of safety concerns and the long-term stability of the regenerated bone are encouraging and justify the launch of larger controlled clinical trials to confirm efficacy and define optimal clinical indications. From a broader perspective, this study highlights the potential of autologous, cell-based bone substitutes as a new generation of personalized regenerative therapies. If confirmed, this approach could reduce the need for painful bone harvesting procedures and improve recovery for patients suffering from difficult bone lesions.
Authors:
Torsten Gerich, M.D., Pierre-Louis Docquier, M.D., Ph.D., John A. Carrino, M.D., M.P.H., F.A.C.R., Mikael Boesen, M.D., Ph.D., Nadine Schmid, M.D., Ginny Hsu, B.D.S., M.S., Jihye Yea, Ph.D., Aaron James, M.D., Ph.D., Judy Ashworth, M.D. Hara Episkopou, Ph.D., and Denis Dufrane, M.D.Ph.D.