Bioreactor Systems for Human Bone Tissue Engineering

Abstract

Critical size skeletal defects resulting from trauma and pathological disorders still remain a major clinical problem worldwide. Bone engineering aims at generating unlimited amounts of viable tissue substitutes by interfacing osteocompetent cells of different origin and developmental stage with compliant biomaterial scaffolds, and culture the cell/scaffold constructs under proper culture conditions in bioreactor systems. Bioreactors help supporting efficient nutrition of cultured cells and allow the controlled provision of biochemical and biophysical stimuli required for functional regeneration and production of clinically relevant bone grafts. In this review, the authors report the advances in the development of bone tissue substitutes using human cells and bioreactor systems. Principal types of bioreactors are reviewed, including rotating wall vessels, spinner flasks, direct and indirect flow perfusion bioreactors, as well as compression systems. Specifically, the review deals with: (i) key elements of bioreactor design; (ii) range of values of stress imparted to cells and physiological relevance; (iii) maximal volume of engineered bone substitutes cultured in different bioreactors; and (iv) experimental outcomes and perspectives for future clinical translation.

Rapid Prototyping Assisted Scaffold Fabrication for Bone Tissue Regeneration

“…Both in vitro and in vivo results showed proliferation and ectopic bone calcification respectively in mice (Zhang et al, 2010). Also, BM-MSCs seeded on poly (lactic -co-glycolic acid) /PCL cylindrical scaffold cultured in perfusion flask for 10 days prior to implantation in the femoral condyle of nude mice shows increase bone formation when compared with static culture (Sladkova & Maria de Peppo, 2014).…”

“…Bioreactors provide the 3D dynamic and mechanical in vivo body environment. They are designed to provide all necessary nutrients and biological cues to the cells seeded deep within a scaffold for its survival, proliferation and differentiation to prodeuce extracellular matrix (Sladkova & Maria de Peppo, 2014). It has been seen in a study that extracellular matrix (ECM) gets uniformly distributed in 3D scaffold by using flow perfusion bioreactor after the period of 16 days in comparison to static condition in the presence of osteogenic cells (Zhang et al, 2010).…”

3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor

“…The thorough combination of computer-aided design, in silico modeling, and in vitro experiments presented here resulted in the development of a 3D printed network which provided adequate levels of oxygen throughout a TEB construct of more than 20 cm 3 , or twice the size of any current TEB constructs 7 to support the viability of differentiating human mesenchymal stem cells. Furthermore, the potential efficacy of tissue engineered bone constructs as implants that can be utilized for direct anastomosis was demonstrated by perfusing fully aggregated constructs for the first time.…”

“…4 Because of these complications, there is a significant clinical need for engineered bone graft substitutes. However, conventional tissue engineering techniques have so far been limited to tissue engineered constructs of less than 11 cubic centimeters 7 . Current research is limited by the need to implant large-scale tissue engineered bone (TEB) constructs with the necessary vasculature for long-term graft functionality.…”

Special Issue: Design of Bioreactor Systems for Tissue Engineering

“…This Special Issue contains a comprehensive review of bioreactor systems, as applied to human bone tissue production. Sladkova and de Peppo [2] report how bioreactor systems have helped to advance the culture of cells on scaffolds. They discuss the principle types of bioreactors, considerations of their design and physiological relevance, and the perspectives for clinical translation.…”