Dataset Information

Size does matter: an integrative in vivo-in silico approach for the treatment of critical size bone defects.

ABSTRACT: Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non-union. In this work, we use an integrative in vivo-in silico approach to investigate the occurrence of non-unions, as well as to design possible treatment strategies thereof. The gap size of the domain geometry of a previously published mathematical model was enlarged in order to study the complex interplay of blood vessel formation, oxygen supply, growth factors and cell proliferation on the final healing outcome in large bone defects. The multiscale oxygen model was not only able to capture the essential aspects of in vivo non-unions, it also assisted in understanding the underlying mechanisms of action, i.e., the delayed vascularization of the central callus region resulted in harsh hypoxic conditions, cell death and finally disrupted bone healing. Inspired by the importance of a timely vascularization, as well as by the limited biological potential of the fracture hematoma, the influence of the host environment on the bone healing process in critical size defects was explored further. Moreover, dependent on the host environment, several treatment strategies were designed and tested for effectiveness. A qualitative correspondence between the predicted outcomes of certain treatment strategies and experimental observations was obtained, clearly illustrating the model's potential. In conclusion, the results of this study demonstrate that due to the complex non-linear dynamics of blood vessel formation, oxygen supply, growth factor production and cell proliferation and the interactions thereof with the host environment, an integrative in silico-in vivo approach is a crucial tool to further unravel the occurrence and treatments of challenging critical sized bone defects.

SUBMITTER: Carlier A

PROVIDER: S-EPMC4222588 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Size does matter: an integrative in vivo-in silico approach for the treatment of critical size bone defects.

Carlier Aurélie A van Gastel Nick N Geris Liesbet L Carmeliet Geert G Van Oosterwyck Hans H

PLoS computational biology 20141106 11

Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non-union. In this work, we use an integrative in vivo-in silico approach to investigate the occurrence of non-unions, as well as to design possible treatment strategies thereof. The gap size of the domain geometry of a previously published mathematical model was enlarged in order to study the complex i ...[more]

PMID: 25375821

Similar Datasets

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

Size does matter: an integrative in vivo-in silico approach for the treatment of critical size bone defects.

Publications

Size does matter: an integrative in vivo-in silico approach for the treatment of critical size bone defects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets