Clinical, Morphological, and Molecular Evaluations of Bone Regeneration With an Additive Manufactured Osteosynthesis Plate

Abstract

There is limited information on the biological status of bone regenerated with microvascular fibula flap combined with biomaterials. This paper describes the clinical, histological, ultrastructural, and molecular picture of bone regenerated with patient-customized plate, used for mandibular reconstruction in combination with microvascular osteomyocutaneous fibula flap. The plate was virtually planned and additively manufactured using electron beam melting. This plate was retrieved from the patient after 33 months. Microcomputed tomography, backscattered-scanning electron microscopy, histology, and quantitative-polymerase chain reaction were employed to evaluate the regenerated bone and the flap bone associated with the retrieved plate. At retrieval, the posterior two-thirds of the plate were in close adaptation with the underlying flap, whereas soft tissue was observed between the native mandible and the anterior one-third. The histological and structural analyses showed new bone regeneration, ingrowth, and osseointegration of the posterior two-thirds. The histological observations were supported by the gene expression analysis showing higher expression of bone formation and remodeling genes under the posterior two-thirds compared with the anterior one-third of the plate. The observation of osteocytes in the flap indicated its viability. The present data endorse the suitability of the customized, additively manufactured plate for the vascularized fibula mandibular reconstruction. Furthermore, the combination of the analytical techniques provides possibilities to deduce the structural and molecular characteristics of bone regenerated using this procedure.

Evidence that Osteocytes in Autogenous Bone Fragments can Repair Disrupted Canalicular Networks and Connect with Osteocytes in de novo Formed Bone on the Fragment Surface

“…Osteoclasts on the surface of autogenous fresh rib grafts are observed in close contact with the cytoplasmic processes of apparently viable osteocytes within the graft [ 5 ]. Viable osteocytes have also been reported within a microvascular fibula flap used in combination with an additively manufactured osteosynthesis plate after 33 months in the human mandible [ 6 ]. Both viable and apoptotic osteocytes can recruit osteoclasts to sites of bone remodelling [ 7 ].…”

<p>Present and future for technologies to develop patient-specific medical devices: a systematic review approach</p>

“…The integration of BIOCAD + CAD + RP + CAM was observed in 10 cases 3,39,62–69. These works focused on 3D printing of biomodels to perform diagnostics, visualize bone defects, and define the surgical approach for cases on the skull and orbital area.…”

“…Some authors claim that the integration of tools for rapid design and manufacture are economically sustainable,60,61 specifically identifying 3D printing as an accessible, accurate, and profitable resource 22,41,60. Other authors claim that barriers such as the high cost of 3D printing61 and increased manufacturing time will keep the implementation of these technologies low 3,10,19,35,60,62,95…”

“…Universal implementation of 3D printing depends on the advancement of the technology, availability of freeware resources, and familiarity of surgeons, designers, and engineers with the technique 56. However, anticipating the demand or number of cases that could use this technique over a certain time period is a complex task 3. Despite the recognized time savings and accuracy, there is still a lack of pedagogy to enable PST as a standardized approach 39…”

Analysis of the miRNA and mRNA involved in osteogenesis of adipose‑derived mesenchymal stem cells

“…Bone is an organ that has the potential for persistent regeneration into adult life and is the only tissue that undergoes constant remodeling throughout life ( 1 ). Efficacious bone regeneration could influence the management of bone and musculoskeletal-associated disorders ( 2 , 3 ). While most fractures recover spontaneously, problems in this regenerative process may result in a variety of diseases.…”