A Medical-Grade Polycaprolactone and Tricalcium Phosphate Scaffold System With Corticoperiosteal Tissue Transfer for the Reconstruction of Acquired Calvarial Defects in Adults: Protocol for a Single-Arm Feasibility Trial

Abstract

Background Large skull defects present a reconstructive challenge. Conventional cranioplasty options include autologous bone grafts, vascularized bone, metals, synthetic ceramics, and polymers. Autologous options are affected by resorption and residual contour deformities. Synthetic materials may be customized via digital planning and 3D printing, but they all carry a risk of implant exposure, failure, and infection, which increases when the defect is large. These complications can be a threat to life. Without reconstruction, patients with cranial defects may experience headaches and stigmatization. The protection of the brain necessitates lifelong helmet use, which is also stigmatizing. Objective Our clinical trial will formally study a hybridized technique's capacity to reconstruct large calvarial defects. Methods A hybridized technique that draws on the benefits of autologous and synthetic materials has been developed by the research team. This involves wrapping a biodegradable, ultrastructured, 3D-printed scaffold made of medical-grade polycaprolactone and tricalcium phosphate in a vascularized, autotransplanted periosteum to exploit the capacity of vascularized periostea to regenerate bone. In vitro, the scaffold system supports cell attachment, migration, and proliferation with slow but sustained degradation to permit host tissue regeneration and the replacement of the scaffold. The in vivo compatibility of this scaffold system is robust—the base material has been used clinically as a resorbable suture material for decades. The importance of scaffold vascularization, which is inextricably linked to bone regeneration, is underappreciated. A variety of methods have been described to address this, including scaffold prelamination and axial vascularization via arteriovenous loops and autotransplanted flaps. However, none of these directly promote bone regeneration. Results We expect to have results before the end of 2023. As of December 2020, we have enrolled 3 participants for the study. Conclusions The regenerative matching axial vascularization technique may be an alternative method of reconstruction for large calvarial defects. It involves performing a vascularized free tissue transfer and using a bioresorbable, 3D-printed scaffold to promote and support bone regeneration (termed the regenerative matching axial vascularization technique). This technique may be used to reconstruct skull bone defects that were previously thought to be unreconstructable, reduce the risk of implant-related complications, and achieve consistent outcomes in cranioplasty. This must now be tested in prospective clinical trials. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12620001171909; https://tinyurl.com/4rakccb3 International Registered Report Identifier (IRRID) DERR1-10.2196/36111

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

“…Preclinical studies to increase research reproducibility [260,263] and for clinical studies in general in the field of large bone defect treatment using 3D-printed scaffolds can only be performed in purposefully planned and well-powered multicentre large-scale collaborative research projects to have the possibility to correct confounding factors related to host and soft tissue while investigating the respective implant for different defect sizes or for different surgical indications [157,264,265]. Furthermore, as bone defects are rare but very complex diseases with a dramatic socio-economic impact on the healthcare system, there are many open questions that may be better understood in the future through the use of artificial intelligence methods-from predictive models and cost analyses to personalised treatment strategies [266]; however, these methods first need to be validated in preclinical and clinical studies.…”

An innovative intramedullary bone graft harvesting concept as a fundamental component of scaffold-guided bone regeneration: A preclinical in vivo validation

“…Moreover, the mPCL-HA Voronoi scaffolds tested in this study exhibited a higher modulus of elasticity than the mPCL composite scaffolds currently used clinically for the treatment of long bone defects and 3D-printed with a rectilinear filling pattern [ 2 , 3 ] (Young's modulus of 22.2 MPa [ 16 ]). Stress–strain curves in the present study were observed to have very similar deformation behaviour to the PCL-tricalcium phosphate (wt 80 %:20 %) scaffolds with rectilinear layer structure [ 44 ], which have already been successfully used in clinical practice [ 2 , 3 , 45 , 46 ]. Complemented by an observed porosity of >50 % of the mPCL-HA Voronoi scaffolds, which we know to be fundamentally capable of facilitating the necessary neovascularization and new (bone) tissue formation [ 2 , 3 , 6 ], we have assessed the scaffolds as suitable for investigating and comparing different scaffold-BG constructs.…”