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. 2023 Aug 8:11:1228250.
doi: 10.3389/fbioe.2023.1228250. eCollection 2023.

Sustained delivery of osteogenic growth peptide through injectable photoinitiated composite hydrogel for osteogenesis

Beibei Liu  1   2 , Jiannan Wu  1   2 , Xiaodi Sun  1   2 , Qingxun Meng  1   2 , Jian Zhang  1   2
Affiliations

Sustained delivery of osteogenic growth peptide through injectable photoinitiated composite hydrogel for osteogenesis

Beibei Liu et al. Front Bioeng Biotechnol. .

Abstract

One of the most challenging clinical issues continues to be the effective bone regeneration and rebuilding following bone abnormalities. Although osteogenic growth peptide (OGP) has been proven to be effective in promoting osteoblast activity, its clinical application is constrained by abrupt release and easily degradation. We developed a GelMA/HAMA dual network hydrogel loaded with OGP based on a combination of physical chain entanglement and chemical cross-linking effects to produce an efficient long-term sustained release of OGP. The hydrogel polymers were quickly molded under ultraviolet (UV) light and had the suitable physical characteristics, porosity structure and biocompatibility. Significantly, the GelMA/HAMA-OGP hydrogel could promote cell proliferation, adhesion, increase osteogenic-related gene and protein expression in vitro. In conclusion, the OGP sustained-release system based on GelMA/HAMA dual network hydrogel offers a fresh perspective on bone regeneration therapy.

Keywords: GelMA; HAMA; OGP; bone tissue engineering; photo-crosslinking; sustained release.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic illustration of the fabrication procedures of the GelMA/HAMA-OGP hydrogels.
FIGURE 2
FIGURE 2
(A) Transformation of sol to gel after UV exposure. (B) The hydrogel can be made into different shapes of hydrogel materials in different modulus. (C) The GelMA/HAMA-OGP hydrogel injected via an 18-gauge needle (φ ≈ 1.20 mm). (D) Gelation time of GelMA/HAMA and GelMA/HAMA-OGP hydrogels. (E) Porosity of GelMA/HAMA with or without OGP loading. (F) SEM images of the porous structure of GelMA/HAMA and GelMA/HAMA-OGP. (ns, no significant difference).
FIGURE 3
FIGURE 3
(A) The ESI-MS spectrum of OGP. (B) HPLC profiles of OGP with high purity (>99%). (C) FTIR spectra of GelMA and GelMA-OGP. (D) FTIR spectra of HAMA and HAMA-OGP. (E) Temperature-dependent viscosity ranging from 10°C to 60°C for different hydrogel. (F) Shear-rate-dependent viscosity ranging from 0.1 to 100 s−1 for different hydrogel composites at 37°C. (G) The fluctuation of storage modulus (G′) and loss modulus (G″) with frequency (ω; rad/s) allowed for the frequency sweep. (H) Swelling, (I) Degradation profiles of GelMA/HAMA, with or without OGP loading. (J) Cumulative release of OGP from the GelMA/HAMA-OGP hydrogel.
FIGURE 4
FIGURE 4
(A) Cell viability of MC3T3-E1 after cultivated on three groups for 1,3, 5 and 7 days evaluated by CCK-8 assay. (ns, no significant difference). (B) Calcein AM/PI staining: Green (Calcein AM) shows live cells, Red (EthD-1) shows dead cells. Scale bar = 500 μm. (C) MC3T3-E1 attachment and spreading behavior on different hydrogel samples was assessed by phalloidin and DAPI staining.
FIGURE 5
FIGURE 5
(A) Representative gross-micrographs of ALP staining on day 7. Scale bar = 500 μm. (B) Representative gross-micrographs of alizarin red staining on day 14. Scale bar = 500 μm. (C) Semi-quantitative analysis of ALP activity for 7 days. (D) Semi-quantitative analysis of alizarin red staining for 14 days. (**p < 0.01, ***p < 0.001, ****p < 0.0001)
FIGURE 6
FIGURE 6
RT-PCR analysis of osteogenesis-related gene expressions including (A) ALP, (B) RUNX2, (C) OCN, (D) OPN, (E) Osterix. Statistically significant differences are indicated with *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
FIGURE 7
FIGURE 7
Representative immunocytochemistry images of osteogenesis-related protein including (A) RUNX-2, (B) Osterix and (C) OPN. (D) Semi-quantitative analysis of fluorescence intensity. Statistically significant differences are indicated with **p < 0.01, ***p < 0.001.
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