Abstract
Hyaluronic acid (HA) has been utilized for a variety of regenerative medical procedures due to its widespread presence in connective tissue and perceived biocompatibility. The aim of the present study was to investigate HA in combination with recombinant human bone morphogenetic protein 9 (rhBMP9), one of the most osteogenic growth factors of the BMP family. HA was first combined with rhBMP9 and assessed for the adsorption and release of rhBMP9 over 10 days by ELISA. Thereafter, ST2 pre-osteoblasts were investigated by comparing (1) control tissue culture plastic, (2) HA alone, and (3) HA with rhBMP9 (100 ng/mL). Cellular proliferation was investigated by a MTS assay at one, three and five days and osteoblast differentiation was investigated by alkaline phosphatase (ALP) activity at seven days, alizarin red staining at 14 days and real-time PCR for osteoblast differentiation markers. The results demonstrated that rhBMP9 adsorbed within HA scaffolds and was released over a 10-day period in a controlled manner. While HA and rhBMP9 had little effect on cell proliferation, a marked and pronounced effect was observed for cell differentiation. rhBMP9 significantly induced ALP activity, mRNA levels of collagen1α2, and ALP and osteocalcin (OCN) at three or 14 days. HA also demonstrated some ability to induce osteoblast differentiation by increasing mRNA levels of OCN and increasing alizarin red staining at 14 days. In conclusion, the results from the present study demonstrate that (1) HA may serve as a potential carrier for various growth factors, and (2) rhBMP9 is a potent and promising inducer of osteoblast differentiation. Future animal studies are now necessary to investigate this combination approach in vivo.
Highlights
Bone morphogenetic proteins (BMPs) have played a pivotal role in modern medicine by directly influencing the commitment and differentiation of osteoprogenitor cells towards osteoblasts [1].When combined with various tissue engineering strategies, they guide the induction of mesenchymal progenitor cells to differentiate towards bone-forming osteoblasts
Thereafter, recombinant human bone morphogenetic protein 9 (rhBMP9) was incorporated into the Hyaluronic acid (HA) and the quantity of total BMP9 released over a 10-day period was observed (Figure 2)
It was first found that at early time points, HA maintained a 70% concentration of BMP9 within its scaffold when compared to original loading (Figure 2). rhBMP9 was released from 70% to 40% within the first 24 h, and thereafter was slowly released up to a 10-day period (Figure 2)
Summary
Bone morphogenetic proteins (BMPs) have played a pivotal role in modern medicine by directly influencing the commitment and differentiation of osteoprogenitor cells towards osteoblasts [1].When combined with various tissue engineering strategies, they guide the induction of mesenchymal progenitor cells to differentiate towards bone-forming osteoblasts. Cheng et al demonstrated that alkaline phosphatase activity (a marker for osteoblast differentiation) was highest in BMP9 whereas Kang et al reported that both BMP-6 and -9 had greater in vivo potential for ectopic bone formation [5,6]. Since those studies utilized adenovirus transfection experiments (an area of research still not approved by the food and drug administration (FDA) [7], translating these results into a clinical setting has not been attempted
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