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. 2023 Dec 6:23:100882.
doi: 10.1016/j.mtbio.2023.100882. eCollection 2023 Dec.

Photo-crosslinked bioactive BG/BMSCs@GelMA hydrogels for bone-defect repairs

Yufeng Ai  1   2   3   4 , Fang Dai  1   2   3 , Wenfeng Li  1   2   3 , Fancheng Xu  1   2   3   4 , Hanwen Yang  4 , Jianxin Wu  1   2   3   4 , Kaiqiang Yang  1   2   3   4 , Li Li  1   2   3   4 , Fanrong Ai  5 , Li Song  1   2   3
Affiliations

Photo-crosslinked bioactive BG/BMSCs@GelMA hydrogels for bone-defect repairs

Yufeng Ai et al. Mater Today Bio. .

Abstract

The clinical treatments of bone defects remain a challenge. Hydrogels containing bone marrow mesenchymal stem cells (BMSCs) are extensively used to bone regeneration because of excellent biocompatibility and hydrophilicity. However, the insufficient osteo-induction capacity of the BMSC-loaded hydrogels limits their clinical applications. In this study, bio-active glass (BG) and BMSCs were combined with gelatin methacryloyl (GelMA) to fabricate composite hydrogels via photo-crosslinking, and the regulation of bone regeneration was investigated. In vitro experiments showed that the BG/BMSCs@GelMA hydrogel had excellent cytocompatibility and promoted osteogenic differentiation in BMSCs. Furthermore, the BG/BMSCs@GelMA hydrogel was injected into critical-sized calvarial defects, and the results further confirmed its excellent angiogenetic and bone regeneration capacity. In addition, BG/BMSCs@GelMA promoted the polarization of macrophages towards the M2 phenotype. In summary, this novel composite hydrogel demonstrated remarkable potential for application in bone regeneration due to its immunomodulatory, excellent angiogenetic as well as osteo-induction capacity.

Keywords: BMSCs; Bio-active glass; Bone regeneration; GelMA.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Characterization of hydrogels. (A) Cross-section image of hydrogel (SEM). (B) SEM images in the different groups. (C) Degradation properties of GelMA and BG@GelMA hydrogel in vitro. (D) Dynamic swelling behaviors of GelMA and BG@GelMA hydrogel in vitro. (E) Stress when the hydrogel strain reaches 50 % after UV crosslinking. (F) The compressive modulus of hydrogels after UV crosslinking. The data presented as mean ± SD, n = 3. *P < 0.05, **P < 0.01 and ***P < 0.001.
Fig. 2
Fig. 2
In vitro evaluation of the cytocompatibility of the hydrogel. (A) Calcein-AM/PI staining. (B) Proliferation of BMSCs in different hydrogels. (C) Cell survival rate. Data presented as mean ± SD, n = 4. *P < 0.05, ****P < 0.0001.
Fig. 3
Fig. 3
Osteogenic differentiation of BMSCs in hydrogels. (A) ALP staining at day 7 (A) and 14 (B). (C) ALP activity assays at day 7 and 14. ARS at days 14 (D) and 21 (E). (F) Quantitative analysis of ARS.
Fig. 4
Fig. 4
(A) ALP staining of the MSCs co-cultured at day 7. (B) ARS staining of the MSCs co-cultured at day 14. (C) Quantitative analysis of ARS. Relative mRNA-expression levels of ALP (D) and RUNX2 (E) in BMSCs.
Fig. 5
Fig. 5
Imaging evaluation 3 and 7 d after surgery in calvarial defect. Micro-CT images for 3 (A) and 7 d (B).
Fig. 6
Fig. 6
Histological analysis at 3 and 7 d after implantation in rat calvarial defect. H&E and Masson's trichrome staining at 3 d (A, B) and 7 d (C, D). Area of neovascularization at day 7 (E), 28 (F), and 56 (G) after implantation, respectively. Area of collagen (% total area) at 7 d (H).
Fig. 7
Fig. 7
Imaging evaluation 4 and 8 w after surgery in calvarial defect. Micro-CT images for 4 weeks (A) and sagittal images (B). BV/TV (C) and BMD (D) after 4 weeks. Micro-CT images for 8 weeks (E) and sagittal images (F). BV/TV (G) and BMD (H) after 8 weeks. Red dotted circle indicates the bone defect area. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 8
Fig. 8
Histological analysis at 4 and 8 w after implantation in rat calvarial defect. H&E and Masson's trichrome staining at 4 w (A, B) and 8 w (E, F). Percentage of new bone area in H&E at 4 w (C) and 8 w (G). Percentage of collagen area in Masson's trichrome at 4 w (D) and 8 w (H).
Fig. 9
Fig. 9
Immunofluorescence staining in vivo. Immunostaining for CD31 (A), OCN (B) and OPN (C) at 4 weeks. Quantitative analysis of CD31 (D), OCN (E) and OPN (F) at 4 weeks. Immunostaining for CD31 (G), OCN (H) and OPN (I) at 8 weeks. Quantitative analysis of CD31 (J), OCN (K) and OPN (L) at 8 weeks.
Fig. 10
Fig. 10
Immunofluorescence staining analysis. Immunofluorescence staining images of iNOS (A) and CD206 (B) in rats following different treatments, and orresponding expression analysis of iNOS (C), and CD206 (D). Ratio of expression of CD206 (M2) to iNOS (M1) (E).
Fig. 11
Fig. 11
Schematic illustration of in vivo evaluation. H&E Staining of organs implanted with GelMA-BG@GelMA (A) and BMSCs@GelMA-BG/BMSCs@GelMA(B) for 4 weeks, and GelMA-BG@GelMA(C) and BMSCs@GelMA-BG/BMSCs@GelMA(D) for 8 weeks (bar = 400 μm).
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