Abstract
The growing occurrence of bone disorders and the increase in aging population have resulted in the need for more effective therapies to meet this request. Bone tissue engineering strategies, by combining biomaterials, cells, and signaling factors, are seen as alternatives to conventional bone grafts for repairing or rebuilding bone defects. Indeed, skeletal tissue engineering has not yet achieved full translation into clinical practice because of several challenges. Bone biofabrication by additive manufacturing techniques may represent a possible solution, with its intrinsic capability for accuracy, reproducibility, and customization of scaffolds as well as cell and signaling molecule delivery. This review examines the existing research in bone biofabrication and the appropriate cells and factors selection for successful bone regeneration as well as limitations affecting these approaches. Challenges that need to be tackled with the highest priority are the obtainment of appropriate vascularized scaffolds with an accurate spatiotemporal biochemical and mechanical stimuli release, in order to improve osseointegration as well as osteogenesis.
Highlights
Bone is composed of bone tissue and bone marrow encased within the periosteum, a thin strip of soft tissue that envelops the midshafts of long bones, extending to their proximal and distal metaphyses and adjacent epiphyses (Malizos and Papatheodorou, 2005)
Fedorovich et al (2008) demonstrated the possibility to generate with this procedure bone grafts by depositing three dimensional (3D) fibers composed of various hydrogels and goat bone marrow stromal cells (BM-mesenchymal stromal cells (MSCs)) with no damage to cells in term of osteogenic differentiation during the printing process
There are still significant challenges with biofabrication for the development of clinically relevant bone constructs. These problems are relative to the existing limitations in ADDITIVE MANUFACTURING TECHNOLOGIES (AMTs) but are due to the possibility to obtain an appropriate vascularization of the structures as well as correct spatiotemporal biochemical and mechanical stimuli, to maximize osteogenesis and osseointegration
Summary
Bone is composed of bone tissue and bone marrow encased within the periosteum, a thin strip of soft tissue that envelops the midshafts of long bones, extending to their proximal and distal metaphyses and adjacent epiphyses (Malizos and Papatheodorou, 2005). Fedorovich et al (2008) demonstrated the possibility to generate with this procedure bone grafts by depositing 3D fibers composed of various hydrogels and goat BM-MSCs with no damage to cells in term of osteogenic differentiation during the printing process In another study, they developed heterogeneous hydrogel constructs with endothelial progenitor cells and goat multipotent stromal cells to promote neovascularization during bone regeneration (Fedorovich et al, 2010). Improved bone formation was observed in hydroxyapatite scaffolds with 300–400 μm pore sizes implanted in rats, suggesting that a fast scaffold vascularization determines an osteogenic microenvironment (Klenke et al, 2008; Bai et al, 2010) Conflicting results in these studies stress the limitations of in vitro researches in predicting in vivo results as well as the requirement to assess the best pore sizes for each cell type used for bone tissue engineering. Kang et al (2016) developed such a platform and effectively produced different tissue types in vivo, opening a breakthrough for the clinical
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