ROBUST – Regeneration of osteoporotic bone using stem-cell transplantation

Secondary dislocation and screw perforation after surgical treatment of proximal humeral fractures is a major complication after auto- or allo-graft-based augmentation and leads to pain, functional restrictions and ultimately to re-operation. The aim of this study was to test as a first-in-human trial the feasibility and safety of an augmentation by SVF cells-seeded composite osteogenic grafts in combination with an angle-stable fixation (Philos plate®) for the therapy of osteoporotic proximal humeral fractures.

A phase I Feasibility - Safety Trial

Osteoporotic proximal humeral fractures gain increasing relevance due to demographic aging. Moreover, expectations about the functional outcome rise, since many people are still active and independent in old age. In proximal humeral fractures - a typical example of osteoporotic fractures - secondary dislocations are observed in 30% of the cases despite the use of angle-stable interlocking plates specifically designed for osteoporotic bone. In particular, the surgical fixation of displaced 3- or 4-part fractures, the typical fracture pattern in osteoporotic bone, remains challenging.

A better stability is achieved by augmentation with autologous bone grafts typically taken from the iliac crest. It is a standard procedure in clinical practice. It is however also associated with significant morbidity (pain, infection, secondary fractures) and quantitatively insufficient in many instances.

The aim of this study was a first-in-human trial on the feasibilty and safety of an augmentation with intraoperatively harvested adipose-derived stromal vascular fraction (SVF) cells, seeded inside a composite grafts (namely a fibrin gel and ceramic granules), in combination with an angle-stable fixation (PhilOs plate®) for the treatment of osteoporotic proximal humeral fractures.

Analysis of surgery times and protocol deviations verified the feasibility to implement the treatment in a standard surgery program. Analysis of pain scores and absence of adverse reactions demonstrated the safety of the approach. No implant-related infections were noticed. Tomographic and histological analysis of implant biopsies collected upon plate removal indicated new bone formation inside the implanted grafts.

Future studies will be designed to test efficacy of SVF cell-based grafts for bone fracture augmentation, likely in different clinical indications, where the quality of the regenerated bone is expected to more directly contribute to the clinical outcome.

Publication:

Saxer F and Scherberich A et al. Implantation of Stromal Vascular Fraction Progenitors at Bone Fracture Sites: From a Rat Model to a First-in-Man Study. Stem Cells, 2016. Pubmed.

More info at clinicaltrials.gov

Diagram showing the general principle of the clinical study