Regenerative matching axial vascularisation of absorbable 3D-printed scaffold for large bone defects: A first in human series

Castrisos, George; Matheus, Isabel Gonzalez; Sparks, David S.; Ward, Nicola; Sehu, Marjoree; Wille, Marie‐Luise; Phua, Yun; Savi, Flávia Medeiros; Hutmacher, Dietmar W.; Wagels, Michael

doi:10.1016/j.bjps.2022.02.057

Cited by 35 publications

(43 citation statements)

References 38 publications

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“…More than 60 published clinical cases as well as more than 100,000 mPCL scaffolds being implanted globally confirm both efficacy and safety of the construct (fig. S8) ( 40 – 48 ). Within both the preclinical studies and the clinical case, SGBR was found radiologically and confirmed biomechanically and histologically (Fig.…”

Section: Discussionmentioning

confidence: 99%

Convergence of scaffold-guided bone regeneration principles and microvascular tissue transfer surgery

et al. 2023

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A preclinical evaluation using a regenerative medicine methodology comprising an additively manufactured medical-grade ε-polycaprolactone β-tricalcium phosphate (mPCL-TCP) scaffold with a corticoperiosteal flap was undertaken in eight sheep with a tibial critical-size segmental bone defect (9.5 cm 3 , M size) using the regenerative matching axial vascularization (RMAV) approach. Biomechanical, radiological, histological, and immunohistochemical analysis confirmed functional bone regeneration comparable to a clinical gold standard control (autologous bone graft) and was superior to a scaffold control group (mPCL-TCP only). Affirmative bone regeneration results from a pilot study using an XL size defect volume (19 cm 3 ) subsequently supported clinical translation. A 27-year-old adult male underwent reconstruction of a 36-cm near-total intercalary tibial defect secondary to osteomyelitis using the RMAV approach. Robust bone regeneration led to complete independent weight bearing within 24 months. This article demonstrates the widely advocated and seldomly accomplished concept of “bench-to-bedside” research and has weighty implications for reconstructive surgery and regenerative medicine more generally.

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Section: Discussionmentioning

confidence: 99%

Convergence of scaffold-guided bone regeneration principles and microvascular tissue transfer surgery

et al. 2023

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“…The current trial builds on successful preclinical work performed by our group evaluating this technique in a well-characterised and validated large animal model 17 20 28 and it is supported by a successful clinical experience in a recently published case series. 21 …”

Section: Discussionmentioning

confidence: 99%

“…This prospective trial data will aim to confirm already existing case series data we have reported to date, which suggests that this approach is safe and well tolerated. 21 In terms of safety and tolerability, the methods used in this prospective trial are a variation to conventional standard of care which for these patients may be amputation. Specific reporting on safety and tolerability will include adverse events that occur during the study period as related to both the scaffold and surgical approach.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2023

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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.

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“…This trial will offer critical baseline data against which current and future implants can be compared. Tissue regeneration could be enhanced via scaffold refinements, including additives such as growth factors, osteoprogenitor cells, and vascular networks [35][36][37][38][39]. However, RMAV may always be necessary to optimize tissue regeneration.…”

Section: Study Overviewmentioning

confidence: 99%

“…The regenerative matching approach resulted in the enhanced volume of regenerate bone, as shown on plain x-ray and micro-CT images [20], and equivalent biomechanical torsional stiffness when compared to the approach using bone grafts alone. In December 2019, we performed a first-in-human case study of applied RMAV, wherein a 3D-printed mPCL-TCP scaffold with rhBMP-7 and vascularized corticoperiosteal flaps was used to successfully perform a reconstruction of a large calvarial defect that had failed to heal after conventional cranioplasty [39]. This work builds on our experiences with bone defect reconstructive research, and it will involve the regenerative matching technique.…”

Section: Introductionmentioning

confidence: 99%

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

Matheus¹,

Hutmacher²,

Olson³

et al. 2022

JMIR Res Protoc

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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

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Regenerative matching axial vascularisation of absorbable 3D-printed scaffold for large bone defects: A first in human series

Cited by 35 publications

References 38 publications

Convergence of scaffold-guided bone regeneration principles and microvascular tissue transfer surgery

Convergence of scaffold-guided bone regeneration principles and microvascular tissue transfer surgery

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

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

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