Abstract
Human adipose-derived stem cells (hADSCs) have the capacity for osteogenic differentiation and, in combination with suitable biomaterials and growth factors, the regeneration of bone defects. In order to differentiate hADSCs into the osteogenic lineage, bone morphogenetic proteins (BMPs) have been proven to be highly effective, especially when expressed locally by route of gene transfer, providing a constant stimulus over an extended period of time. However, the creation of genetically modified hADSCs is laborious and time-consuming, which hinders clinical translation of the approach. Instead, expedited single-surgery gene therapy strategies must be developed. Therefore, in an in vitro experiment, we evaluated a novel growth factor delivery system, comprising adenoviral BMP-2 transduced fascia tissue in terms of BMP-2 release kinetics and osteogenic effects, on hADSCs seeded on an innovative biomimetic spongiosa-like scaffold. As compared to direct BMP-2 transduction of hADSCs or addition of recombinant BMP-2, overexpressing fascia provided a more uniform, constant level of BMP-2 over 30 days. Despite considerably higher BMP-2 peak levels in the comparison groups, delivery by overexpressing fascia led to a strong osteogenic response of hADSCs. The use of BMP-2 transduced fascia in combination with hADSCs may evolve into an expedited single-surgery gene transfer approach to bone repair.
Highlights
Trauma and bone disease frequently result in fractures or large critical bone defects, and their management often necessitates the substitution of bone
We have discovered that fascia tissue fragments can be readily transduced with adenoviral vectors, leading to bone morphogenetic proteins (BMPs)-2 expression with nanogram quantities for at least 90 days in vitro
The goal of the present study was to evaluate the capability of genetically modified fascia tissue to serve as a delivery system for BMP-2inducing osteogenesis in Human adipose-derived stem cells (hADSCs) seeded on a biomimetic spongiosa-like scaffold
Summary
Trauma and bone disease frequently result in fractures or large critical bone defects, and their management often necessitates the substitution of bone. Traditional therapies include autograft and allograft transplantation, of which autologous bone transplantation is recognized as the clinical “gold standard” since all the essential requirements for bone regeneration in terms of osteoconduction, osteoinduction and osteogenesis are satisfied [1,2]. In addition to the limited availability of bone autograft, chronic pain and donor site morbidity limit the effectiveness of this option. Allograft is widely available, the problems of resorption, immune reaction and disease transmission restrict its application [3,4]. Attempts have been made to identify effective alternative methods, but there is still no consensus on an ideal therapy. Available osseous substitutes fall short of achieving a robust and reliable bone formation clinically
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