Protocol for the BONE-RECON trial: a single-arm feasibility trial for critical sized lower limb BONE defect RECONstruction using the mPCL-TCP scaffold system with autologous vascularised corticoperiosteal tissue transfer

Abstract

IntroductionReconstruction of critical bone defects is challenging. In a substantial subgroup of patients, conventional reconstructive techniques are insufficient. Biodegradable scaffolds have emerged as a novel tissue engineering strategy for critical-sized bone defect reconstruction. A corticoperiosteal flap integrates the hosts’ ability to regenerate bone and permits the creation of a vascular axis for scaffold neo-vascularisation (regenerative matching axial vascularisation—RMAV). This phase IIa study evaluates the application of the RMAV approach alongside a custom medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold (Osteopore) to regenerate bone sufficient to heal critical size defects in lower limb defects.Methods and analysisThis open-label, single-arm feasibility trial will be jointly coordinated by the Complex Lower Limb Clinic (CLLC) at the Princess Alexandra Hospital in Woolloongabba (Queensland, Australia), the Australian Centre for Complex Integrated Surgical Solutions (Queensland, Australia) and the Faculty of Engineering, Queensland University of Technology in Kelvin Grove (Queensland, Australia). Aiming for limb salvage, the study population (n=10) includes any patient referred to the CLLC with a critical-sized bone defect not amenable to conventional reconstructive approaches, after discussion by the interdisciplinary team. All patients will receive treatment using the RMAV approach using a custom mPCL-TCP implant. The primary study endpoint will be safety and tolerability of the reconstruction. Secondary end points include time to bone union and weight-bearing status on the treated limb. Results of this trial will help shape the role of scaffold-guided bone regenerative approaches in complex lower limb reconstruction where current options remain limited.Ethics and disseminationApproval was obtained from the Human Research Ethics Committee at the participating centre. Results will be submitted for publication in a peer-reviewed journal.Trial registration numberACTRN12620001007921.

The Concept of Scaffold-Guided Bone Regeneration for the Treatment of Long Bone Defects: Current Clinical Application and Future Perspective

“…However, a recent phase IIa clinical trial registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) using the RMAV approach [conducted in Brisbane, Australia, at a major trauma centre (ANZCTR No. 12620001007921)] [245], provides hope for future results of larger clinical trials of 3Dprinted scaffolds for long bone defects. Nonetheless, as described earlier by Hollister and Murphy [238], to routinely establish standardized large-scale multicentre (pre)clinical research efforts, we must first define the goal of BTE and the role that biomaterial implants play in achieving this aim-that is, we must find viable and both clinical and economical approaches to bone regeneration in orthopaedic surgery for long bone defects.…”

Surgical Site-Released Tissue Is Potent to Generate Bone onto TCP and PCL-TCP Scaffolds In Vitro

“…Cylindrical synthetic bone grafts made of ß-tricalcium phosphate (ß-TC M ® , Curasan AG, Kleinostheim, Germany) and tubular composite scaffolds medical-grade poly-ε-caprolactone (PCL) and 20% ß-TCP (mPCL-TCP) (O Ltd., Singapore) were used in this study (Figure 10). Further characteristics site material can be found in the literature [57][58][59][60]. The specimen had an outer diameter of 21 mm, a wall thickness of 3 mm of 50 mm (ß-TCP) and 100 mm (mPCL-TCP).…”

In vivo characterization of 3D-printed polycaprolactone-hydroxyapatite scaffolds with Voronoi design to advance the concept of scaffold-guided bone regeneration

“…Scaffold-guided bone regeneration (SGBR) is a clinically applied concept that has largely improved the treatment of bone defects in the last decade, as demonstrated by the findings from multiple large animal and clinical studies by our research group and others ( Reichert et al, 2012 ; Cipitria et al, 2013 ; Berner et al, 2015 ; Berner et al, 2017 ; Kobbe et al, 2020 ; Henkel et al, 2021 ; Laubach et al, 2022b ; Castrisos et al, 2022 ; Sparks et al, 2023 ). The SGBR concept is based on the application of biodegradable porous implants (or “scaffolds”) that act as carriers for bone grafts ( Hutmacher, 2000 ).…”