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Personalized medicine for reconstruction of critical-size bone defects - a translational approach with customizable vascularized bone tissue.

ABSTRACT: Tissue engineering principles allow the generation of functional tissues for biomedical applications. Reconstruction of large-scale bone defects with tissue-engineered bone has still not entered the clinical routine. In the present study, a bone substitute in combination with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) with or without growth factors BMP-2 and VEGF-A was prevascularized by an arteriovenous (AV) loop and transplanted into a critical-size tibia defect in the sheep model. With 3D imaging and immunohistochemistry, we could show that this approach is a feasible and simple alternative to the current clinical therapeutic option. This study serves as proof of concept for using large-scale transplantable, vascularized, and customizable bone, generated in a living organism for the reconstruction of load-bearing bone defects, individually tailored to the patient's needs. With this approach in personalized medicine for the reconstruction of critical-size bone defects, regeneration of parts of the human body will become possible in the near future.

SUBMITTER: Kengelbach-Weigand A

PROVIDER: S-EPMC8377075 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Personalized medicine for reconstruction of critical-size bone defects - a translational approach with customizable vascularized bone tissue.

Kengelbach-Weigand Annika A Thielen Carolina C Bäuerle Tobias T Götzl Rebekka R Gerber Thomas T Körner Carolin C Beier Justus P JP Horch Raymund E RE Boos Anja M AM

NPJ Regenerative medicine 20210819 1

Tissue engineering principles allow the generation of functional tissues for biomedical applications. Reconstruction of large-scale bone defects with tissue-engineered bone has still not entered the clinical routine. In the present study, a bone substitute in combination with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) with or without growth factors BMP-2 and VEGF-A was prevascularized by an arteriovenous (AV) loop and transplanted into a critical-size tibia defect in the ...[more]

PMID: 34413320

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Project description:Treating critical-size bone defects with autografts, allografts, or standardized implants is challenging since the healing of the defect area necessitates patient-specific grafts with mechanically and physiologically relevant structures. Three-dimensional (3D) printing using computer-aided design (CAD) is a promising approach for bone tissue engineering applications by producing constructs with customized designs and biomechanical compositions. In this study, we propose 3D printing of personalized and implantable hybrid active scaffolds with a unique architecture and biomaterial composition for critical-size bone defects. The proposed 3D hybrid construct was designed to have a gradient cell-laden poly(ethylene glycol) (PEG) hydrogel, which was surrounded by a porous polycaprolactone (PCL) cage structure to recapitulate the anatomical structure of the defective area. The optimized PCL cage design not only provides improved mechanical properties but also allows the diffusion of nutrients and medium through the scaffold. Three different designs including zigzag, zigzag/spiral, and zigzag/spiral with shifting the zigzag layers were evaluated to find an optimal architecture from a mechanical point of view and permeability that can provide the necessary mechanical strength and oxygen/nutrient diffusion, respectively. Mechanical properties were investigated experimentally and analytically using finite element analysis (FEA), and computational fluid dynamics (CFD) simulation was used to determine the permeability of the structures. A hybrid scaffold was fabricated via 3D printing of the PCL cage structure and a PEG-based bioink comprising a varying number of human bone marrow mesenchymal stem cells (hBMSCs). The gradient bioink was deposited inside the PCL cage through a microcapillary extrusion to generate a mineralized gradient structure. The zigzag/spiral design for the PCL cage was found to be mechanically strong with sufficient and optimum nutrient/gas axial and radial diffusion while the PEG-based hydrogel provided a biocompatible environment for hBMSC viability, differentiation, and mineralization. This study promises the production of personalized constructs for critical-size bone defects by printing different biomaterials and gradient cells with a hybrid design depending on the need for a donor site for implantation.

Dataset Information

Personalized medicine for reconstruction of critical-size bone defects - a translational approach with customizable vascularized bone tissue.

Publications

Personalized medicine for reconstruction of critical-size bone defects - a translational approach with customizable vascularized bone tissue.

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