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

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.

Role of hyaluronan in regulating self-renewal and osteogenic differentiation of mesenchymal stromal cells and pre-osteoblasts

“…In vivo, application of HA for bone regeneration has been demonstrated in craniofacial bone defects in various animal models [18]. To stimulate bone formation, HA is either (1) mixed with filler materials [9,10,[19][20][21], (2) applied as a coating material [22], or (3) used as a carrier of growth factors and cells in the bone defect [23][24][25]. However, to date, only few clinical studies exist on the use of HA in reconstructive periodontal surgery [26][27][28][29][30].…”

Hyaluronik asit ve gama radyasyonlu mineralize allogreftlerin sıçan tibial defektlerinin iyileşmesi üzerine etkileri

“…HyA has been shown to play an important role in the healing of bone tissue 21 . Several studies have confirmed the efficacy of HyA on the soft tissues [22][23][24][25] . Studies have more recently focused on the effects of HyA on bone healing.…”

Acceleration of bone union by in situ-formed hydrogel containing bone morphogenetic protein-2 in a mouse refractory fracture model

“…Several studies have examined HA hydrogels for their potential as carriers for BMP-2. Injectable or implantable HA hydrogels retain BMP-2 and stimulate bone formation in vivo [ 17 , 21 – 27 ]. Implantation of acrylated HA hydrogel with BMP-2 accelerates bone repair in calvarial defects in rats, and injectable hydrazone-crosslinked HA hydrogels with BMP-2 stimulate bone formation in rat calvaria [ 28 ].…”

“…Glycosaminoglycans (GAGs) have been shown to improve BMP-2 bioactivity, including for obtaining the intended osteogenesis effects [ 17 ]. HA, a type of GAG, comprises linear polysaccharides made up of repeating disaccharide units of amino sugars and uronic acid, and is among the most used materials for enhancing the microenvironment for BMP-induced osteogenesis.…”