Surgical use of 3D printed cages as adittion for the filling of large bone defects, a randomised controlled trial

Bone defects have a devastating impact on quality of life. The affected limb
cannot be used and the subsequent lack of mobility results in a low
health-related quality of life. Treatment of bone defects is challenging,
especially when infection is present, and frequently ends in an amputation. To
restore bone continuity, bone regeneration has to occur and that requires
several biological and mechanical components. A good soft tissue coverage, the
presence of cells, growth factors and a scaffold are all prerequisites for bone
regeneration in an environment that has to be well vascularized and free of
infection. Nowadays, bone autograft supplemented with bone marrow stem cells
and bone growth factors is the gold standard to improve healing in traumatic
bone defects. However, in larger defects (>5cm) the treatment remains
challenging due to limited scaffolding and treatment-resistant infection.
Application of an innovative, custom made, 3D-printed cage made of poly-*-
caprolactone with ß-tri-calcium phosphate (PCL/TCP) has the potential to
improve the clinical outcome substantially.

To investigate whether the addition of a custom made 3D printed scaffold to
standard treatment increases healing and decreases the need for secondary
surgery in segmental defects of long bones with a length of more than 5 cm
compared to the standard treatment, which consists of a combination of
autologous bone, stem cells, osteoconductive materials and growth factors.

Prospective, single-center randomized clinical trial, single blinded.

The control group will receive the standard treatment for these defects in our
center. This treatment consists of a two-stage surgical procedure called the
Induced Membrane Technique (IMT). During the first stage, the surgical site is
debrided and a cement spacer is placed to initiate the formation of a membrane
around the spacer; a physiological response to the implanted foreign body (the
cement spacer). If deemed necessary, soft tissue coverage via free flap
transfer is performed as well. In the second stage, the spacer is removed and
autograft bone, Reamer Irrigator Aspirator (RIA) derived autograft and Bone
Marrow Aspirate Concentrate (BMAC), and factor P-15 (iFactor, Cerapedics,
Westminster, USA) are applied in the bone defect area. The experimental group
will receive the treatment as described before, combined with a 3D-printed
scaffold consisting of PCL/TCP (Osteopore, Taman Jurong, Singapore).

The choice for the timing of the endpoints is based on regular care in order to
limit the burden for participants. This is also the case for all radiological
examinations including the CT scan at six months. The study requires 2
additional CT scans, the radiation exposure of these scans is lower than the
amount of natural radiation humans are exposed to every year.
Participants will be requested to fill out the above described questionnaires
at each follow-up moment; six weeks, twelve weeks, six months, and one year. We
classify the burden for these questionnaires as minimal in accordance with
previous evaluations by the local ethical committee. The main risks for the
participants are all related to the medical condition of the bone defect and
are, as we foresee, not related to the study participation. In general, these
risks are infection at the surgical site, persistent/permanent pain at the
surgical site, sensory loss or disturbance at the surgical site and, when
utilized, free flap failure.