title: Hyaluronic Acid Gel-Based Scaffolds as Potential Carrier for Growth Factors: An In Vitro Bioassay on Its Osteogenic Potential.
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.
authors.affiliation: Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital, Bern 3010, Switzerland. benoit.schaller@insel.ch.|Department of Oral Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8501, Japan. benoit.schaller@insel.ch.
authors.forename: Masako
authors.initials: M
authors.lastname: Fujioka-Kobayashi
authors.affiliation: Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital, Bern 3010, Switzerland. eizabu@ngt.ndu.ac.jp.
authors.forename: Benoit
authors.initials: B
authors.lastname: Schaller
authors.affiliation: Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
authors.forename: Eizaburo
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Department of Periodontology, Nova Southeastern University, Fort Lauderdale, FL 33328, USA. marher@nova.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Hernandez
authors.affiliation: Department of Oral Implantology, University of Wuhan, Wuhan 430079, China. zyf@whu.edu.cn.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Periodontology, Nova Southeastern University, Fort Lauderdale, FL 33328, USA. rmiron@nova.edu.|Cell Therapy Institute, Center for Collaborative Research, Nova Southeastern University, Fort Lauderdale, FL 33328, USA. rmiron@nova.edu.|Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, MI 48109-1078, USA. rmiron@nova.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miron
keywords: BMP; bone formation; bone induction; dimensional changes; growth factor; guided bone regeneration; hard tissue regeneration; osteoinduction; osteoinductive; regenerative therapy