In Vivo Bone Tissue Engineering Strategies: Advances and Prospects

Abstract

Reconstruction of critical-sized bone defects remains a tremendous challenge for surgeons worldwide. Despite the variety of surgical techniques, current clinical strategies for bone defect repair demonstrate significant limitations and drawbacks, including donor-site morbidity, poor anatomical match, insufficient bone volume, bone graft resorption, and rejection. Bone tissue engineering (BTE) has emerged as a novel approach to guided bone tissue regeneration. BTE focuses on in vitro manipulations with seed cells, growth factors and bioactive scaffolds using bioreactors. The successful clinical translation of BTE requires overcoming a number of significant challenges. Currently, insufficient vascularization is the critical limitation for viability of the bone tissue-engineered construct. Furthermore, efficacy and safety of the scaffolds cell-seeding and exogenous growth factors administration are still controversial. The in vivo bioreactor principle (IVB) is an exceptionally promising concept for the in vivo bone tissue regeneration in a predictable patient-specific manner. This concept is based on the self-regenerative capacity of the human body, and combines flap prefabrication and axial vascularization strategies. Multiple experimental studies on in vivo BTE strategies presented in this review demonstrate the efficacy of this approach. Routine clinical application of the in vivo bioreactor principle is the future direction of BTE; however, it requires further investigation for to overcome some significant limitations.

3D printed strontium–zinc-phosphate bioceramic scaffolds with multiple biological functions for bone tissue regeneration

“…Beyond osteogenesis, angiogenesis is also crucial for the viability of bone scaffolds. 38 Blood vessels inside the bone play a crucial role in bone remodeling and regeneration via providing bone precursor cells. Compared to b-TCP scaffolds, SZP scaffolds were found to lead to promoted proliferation, migration and tube formation of HUVECs, as well as mRNA expression of angiogenic factors bFGF, eNOS and HIF-1a (Fig.…”

Doped Electrospinned Material-Guides High Efficiency Regional Bone Regeneration

“…The composite membranes, in the present research, are loaded with silica nanoparticles to promote their integration with human tissues by inducing scaffold bioactivity and osteoconductivity [ 6 ] and by facilitating surface formation of calcium phosphate deposits [ 7 ]. Vascularization is a key event for bone remodeling and regeneration to occur, since the skeleton depends on the vascular system to maintain its metabolic balance [ 8 , 9 ]. It is widely accepted that vascular development always precedes osteogenesis [ 10 ].…”

Effect of adipose-derived stem cells seeding and surgical prefabrication on composite scaffold vascularization

“…18 Surgical prefabrication that involves placing a fully functional vessel into a scaffold to vascularize it via overgrowing and sprouting seems to be one of the most promising methods for the stimulation of angiogenesis. [19][20][21][22][23][24][25][26][27] Another strategy involves the use of the proangiogenic properties of adipose-derived stem cells (ASCs), which have been proven to effectively stimulate angiogenesis. [28][29][30] The use of both methods at the same time exerts a synergistic effect, as demonstrated in our previous research, in which a poly-ε-caprolactone (PCL) scaffold was surgically prefabricated (vascular pedicle was inserted inside the scaffold) and seeded with ASCs.…”