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.
Highlights
Therapeutic options for bone defects that cannot heal spontaneously, the so-called critical-size bone defects, are still limited and often associated with a great social burden
In preparation for clinical translation, we have further developed the AV loop approach in the present study as an innovative therapeutic option for critical-size bone defects
Typical sprouting of cell spheroids could be seen in a 3D hydrogel after 48 h (Fig. 1c)
Summary
Therapeutic options for bone defects that cannot heal spontaneously, the so-called critical-size bone defects, are still limited and often associated with a great social burden. The gold standard has remained the transplantation of vascularized autologous tissue from an unharmed area of the body, such as the fibula, scapula, or iliac crest[1,2,3]. Patients suffer from donor site morbidities, long hospital stays, or impaired functions of damaged tissue. From the clinical point of view, there is an urgent need to refine present therapeutic options in order to improve patient care. Preclinical data are limited and further proof-of-principle studies are necessary to prepare for the translation of experimental approaches into clinical practice thoroughly
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