Hyaluronic Acid Promotes the Osteogenesis of BMP-2 in an Absorbable Collagen Sponge.

Hairong Huang,Jianying Feng,Daniel Wismeijer,Gang Wu,Ernst Hunziker

doi:10.3390/polym9080339

Abstract

(1) Background: We tested the hypothesis that hyaluronic acid (HA) can significantly promote the osteogenic potential of BMP-2/ACS (absorbable collagen sponge), an efficacious product to heal large oral bone defects, thereby allowing its use at lower dosages and, thus, reducing its side-effects due to the unphysiologically-high doses of BMP-2; (2) Methods: In a subcutaneous bone induction model in rats, we first sorted out the optimal HA-polymer size and concentration with micro CT. Thereafter, we histomorphometrically quantified the effect of HA on new bone formation, total construct volume, and densities of blood vessels and macrophages in ACS with 5, 10, and 20 μg of BMP-2; (3) Results: The screening experiments revealed that the 100 µg/mL HA polymer of 48 kDa molecular weight could yield the highest new bone formation. Eighteen days post-surgery, HA could significantly enhance the total volume of newly-formed bone by approximately 100%, and also the total construct volume in the 10 μg BMP-2 group. HA could also significantly enhance the numerical area density of blood vessels in 5 μg BMP-2 and 10 μg BMP-2 groups. HA did not influence the numerical density of macrophages; and (4) Conclusions: An optimal combined administration of HA could significantly promote osteogenic and angiogenic activity of BMP-2/ACS, thus potentially minimizing its potential side-effects.

Highlights

Recombinant human bone morphogenetic protein-2 (BMP-2) has been in clinical use mainly for the generation of spinal fusions for more than a decade [1,2]
The screening experiments revealed that the hyaluronic acid (HA) polymer of 48 kDa molecular weight was able to yield the highest osteogenesis activity, when applied at a concentration of 100 μg/mL of HA (Figure 1), and with an added BMP-2 amount of 10 μg (BMP-2 concentration in the solution: 1 μg/μL; BMP-solution-volume added: 10 μL/sample)
5, 10 and 20 μg BMP-2 resulted in a similar total volume of newly formed bone tissue, while no bone was detected with or without HA in the absence of BMP-2 (Figure 2)

Summary

Introduction

Recombinant human bone morphogenetic protein-2 (BMP-2) has been in clinical use mainly for the generation of spinal fusions for more than a decade [1,2]. Its clinical use is quite successful; the use of BMP-2 is, associated with a number of severe undesired side effects that are able to seriously impair the health of patients and the musculoskeletal functions of the treated patients [7,8]. Such side-effects include, among others, ectopic bone formation, paralysis, and neurological disturbances [9,10]; but malignant pathologies are not involved [11,12].

Methods

Results

Conclusion