Safety and Efficacy Results of BonoFill First-in-Human, Phase I/IIa Clinical Trial for the Maxillofacial Indication of Sinus Augmentation and Mandibular Bone Void Filling

Abstract

The gold standard for bone regeneration of bone deficiencies is still an autologous bone graft, which has considerable disadvantages; namely, the need for a second major surgery and the limited volume of bone available for harvesting. BonoFill (BF) is a novel, tissue-engineered, bone graft with intrinsic osteoinductive, osteoconductive, and osteogenic properties, consisting of the patient's own adipose tissue-derived mesenchymal stem cells, attached to hydroxyapatite particles. Here, we present the safety and efficacy results of BF first-in-human clinical study for maxillofacial bone tissue regeneration. Eleven eligible male and female subjects, aged 49-65years, were enrolled into the clinical study in 2 clinical indications: Bone augmentation and bone void grafting in the jaws. Clinical follow-up was performed throughout a period of 6 months after BF treatment and included clinical examination, blood tests, CT scans, and biopsies collected from the transplantation site to assess chronic bone infection, changes in complete blood count, and adequate bone augmentation for implant placement. The study results demonstrated that BF promoted adequate bone tissue regeneration without complications. Per our evaluation, there were no incidents of chronic bone infection, or significant changes in complete blood count, and the patients reported overall good health for the duration of the study. At trial end, in the sinus augmentation indication, the BF treated sites residual bone was augmented at an average of 6.36mm (Δ new bone, n=10) and the total bone height at the treated area was on average 11.44mm (n=10). In the indication of filling of bone voids, the patient's average residual bone height of 2.91mm was 15.76mm (n=1) at trial end. BF treatment was shown to be safe and resulted in newly generated bone, which provided adequate bone height for placement of dental implants. Thus, BF is a promising novel autologous bone graft for bone tissue repair.