Biomaterials Translational ›› 2024, Vol. 5 ›› Issue (1): 59-68.doi: 10.12336/biomatertransl.2024.01.006
• RESEARCH ARTICLES • Previous Articles Next Articles
Huaxin Yang1, Mengjia Zheng1, Yuyue Zhang1, Chaochang Li2, Joseph Ho Chi Lai1, Qizheng Zhang1, Kannie WY Chan1, Hao Wang2, Xin Zhao3, Zijiang Yang2,*(), Chenjie Xu1,*()
Received:
2023-12-11
Revised:
2024-01-20
Accepted:
2024-03-08
Online:
2024-03-28
Published:
2024-03-28
Contact:
Chenjie Xu, Figure 1. Fabrication and subcutaneous transplantation of PCL/MeHA composite scaffolds. Created with BioRender.com. MeHA: methacrylated hyaluronic acid; NaCl: sodium chloride; PCL: poly(ε-caprolactone).
Figure 2. Characterisation of rheological properties. (A, B) Storage modulus (G′) and loss modulus (G″) of MeHA solutions (5% (w/w); A) and derived MeHA hydrogels (B). Data corresponded to one experiment. DS: degree of substitution; MeHA: methacrylated hyaluronic acid.
Figure 3. Characterisation of PCL scaffolds. (A) Isotherm linear plot of absorption and desorption of PCL scaffolds with different ratios of PCL and NaCl (number of samples per scaffold, n = 5). (B) BET surface area and pore volume of PCL scaffolds with different ratios of PCL and NaCl (n = 5). (C) Tensile moduli of PCL scaffolds with different ratios of PCL and NaCl (n = 3; three measurements were obtained per scaffold). (D) Compressive moduli of PCL scaffolds with different ratios of PCL and NaCl (n = 3; three measurements were obtained per scaffold). Data are expressed as mean ± SD. **P < 0.01, ****P < 0.0001 (one-way analysis of variance followed by Dunnett’s multiple comparison test). BET: Brunauer-Emmett-Teller; NaCl: sodium chloride; ns: not significant; P: the equilibrium adsorption pressure of the gas; P0: the saturated vapour pressure of the gas at the adsorption temperature; PCL: poly(ε-caprolactone).
Figure 4. Histological evaluation of scaffold sections after four-week implantation in mice. (A) H&E staining results: interaction of scaffolds with surrounding tissues (microscopy images at 4× magnification; the black line segment indicates the fibrotic capsule). (B) Fibrosis thickness of different scaffolds based on images obtained at 4× magnification (samples per implant, n = 3, with five measurements obtained per implant). Data are expressed as mean ± SD. *P < 0.05, ****P < 0.0001 (one-way analysis of variance followed by Dunnett’s multiple comparison test). DS: degree of substitution; H&E: haematoxylin & eosin; MeHA: methacrylated hyaluronic acid; ns: not significant; PCL: poly(ε-caprolactone).
Figure 5. vWF staining results. (A) New blood vessels (microscopy images obtained at magnification of 10× (upper) and 20× (lower)). The square indicates the area chosen for amplification. All of the PCL/MeHA composite scaffolds (regardless of molecular weight and DS) successfully induced angiogenesis similar to the PCL/fibrin scaffolds. The PCL scaffold effectively induced the vascular regeneration. (B) Quantitative analysis of angiogenesis: number of blood vessels associated with different scaffolds based on 10× magnified images (samples per implant, n = 3, with five measurements obtained per implant). Data are expressed as mean ± SD. ****P < 0.0001 (one-way analysis of variance followed by Dunnett’s multiple comparison test). DS: degree of substitution; MeHA: methacrylated hyaluronic acid; ns: not significant; PCL: poly(ε-caprolactone); vWF: von Willebrand factor.
Additional Figure 2. Storage modulus (G′) and loss modulus (G″) of unmodified HA solutions (5% (w/w)). Data corresponded to one experiment. HA: hyaluronic acid.
Additional Figure 3. The swelling behaviors of crosslinked MeHA polymers in PBS. MeHA: methacrylated hyaluronic acid; PBS: phosphate-buffered saline. Data are expressed as mean ± SD.
Additional Figure 4. SEM images of the porous PCL scaffolds prepared by using different PCL/NaCl composition. The pores of all scaffolds exhibited non-uniform sizes and shapes. Scale bars: 200 μm. NaCl: sodium chloride; PCL: poly(ε-caprolactone); SEM: scanning electron microscopy.
Additional Figure 5. Raw data from tensile elastic modulus tests of PCL scaffolds. The curve fitting is calculated by simple linear regression. PCL: poly(ε-caprolactone).
Additional Figure 6. Raw data from compressive elastic modulus tests of PCL scaffolds. The curve fitting is calculated by simple linear regression. PCL: poly(ε-caprolactone).
Additional Figure 7. Cell viability indicated the biocompatibility of PCL/MeHA composite scaffold. (A) Raw data of the value obtained from microplate reader. (B) Calculated cell viability of MSC cultured with scaffolds, compared with positive group. Data are expressed as mean ± SD. MeHA: methacrylated hyaluronic acid; MSC: mesenchymal stem cell; PCL: poly(ε-caprolactone).
Additional Figure 8. The in vivo experiment design and continuous mice body weight record. (A) Flowchart of animal experiment design. (B) Detailed mice label, transplantation site and the type of the implanted scaffold. (C) Continuous body weight record of mice and the trend during the experiment. All mice were healthy, and their weight were stable. DS: degree of substitution; MeHA: methacrylated hyaluronic acid; PCL: poly(ε-caprolactone).
Additional Figure 9. Comparison of angiogenesis situation of all scaffolds before and 4 weeks after transplantation. Images revealed the formation of new blood vessels and fibrotic capsules of different thicknesses around the scaffolds. Notably, the fibrotic capsule around the PCL/DS72–900 MeHA composite scaffolds appeared slightly thicker compared with the others. DS: degree of substitution; MeHA: methacrylated hyaluronic acid; PCL: poly(ε-caprolactone).
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