力学性能增强的聚乙烯醇/丙烯酰胺水凝胶通过旁分泌作用调节免疫和血管化过程以促进皮肤缺损的修复

王鹏, 钱丽萍, 梁绘昕, 黄剑浩, 金晶, 谢春梅, 薛斌, 赖建诚, 张祎博, 蒋利锋, 李澜, 蒋青

工程(英文) ›› 2024, Vol. 37 ›› Issue (6) : 151-165.

PDF(4096 KB)
PDF(4096 KB)
工程(英文) ›› 2024, Vol. 37 ›› Issue (6) : 151-165. DOI: 10.1016/j.eng.2024.02.005
研究论文
Article

力学性能增强的聚乙烯醇/丙烯酰胺水凝胶通过旁分泌作用调节免疫和血管化过程以促进皮肤缺损的修复

作者信息 +

A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion

Author information +
History +

Abstract

Hydrogel- based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin. However, the mechanical properties of hydrogel scaffolds and natural skin are substantially different. Here, we developed a polyvinyl alcohol (PVA)/acrylamide based interpenetrating network (IPN) hydrogel that was surface modified with polydopamine (PDA) and termed Dopa-gel. The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions. Furthermore, a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing. The results showed that the interpenetration of PVA, alginate, and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel. Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors. In an in vivo model, Dopa-gel treatment accelerated wound closure, increased vascularization, and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area. Mechanistically, the focal adhesion kinase (FAK)/extracellular signal-related kinase (ERK) signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel. Additionally, proangiogenic factors can be induced through Rho-associated kinase-2 (ROCK-2)/vascular endothelial growth factor (VEGF)-mediated paracrine secretion under tensile stress conditions. Taken together, these findings suggest that the multifunctional Dopa-gel, which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties, is a promising scaffold for skin tissue regeneration.

Keywords

Polyvinyl alcohol/acrylamide hydrogel / Mechanical property enhancement / Paracrine effect / Skin regeneration / Signaling pathways

引用本文

导出引用
王鹏, 钱丽萍, 梁绘昕. 机械性能增强的聚乙烯醇/丙烯酰胺水凝胶通过旁分泌作用调节免疫和血管化过程促进皮肤缺损的修复. Engineering. 2024, 37(6): 151-165 https://doi.org/10.1016/j.eng.2024.02.005

参考文献

[1]
H. Niu, Y. Guan, T. Zhong, L. Ma, M. Zayed, J. Guan. Thermosensitive and antioxidant wound dressings capable of adaptively regulating TGFβ pathways promote diabetic wound healing. NPJ Regen Med, 8 (1) (2023), p. 32.
[2]
X. Tang, J. Ren, X. Wei, T. Wang, H. Li, Y. Sun, et al. Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch. Nat Commun, 14 (1) (2023), p. 2417.
[3]
L. Chen, Q. Xing, Q. Zhai, M. Tahtinen, F. Zhou, L. Chen, et al. Pre-vascularization enhances therapeutic effects of human mesenchymal stem cell sheets in full thickness skin wound repair. Theranostics, 7 (1) (2017), pp. 117-131.
[4]
M. He, Z. Wang, H. Yang, Q. Wang, D. Xiang, X. Pang, et al. Multi- functional bio-HJzyme: revolutionizing diabetic skin regeneration with its glucose-unlocked sterilization and programmed anti-inflammatory effects. Adv Sci, 10 (21) (2023), p. 2300986.
[5]
Y. Peng, J. Zhou, Y. Yang, J.C. Lai, Y. Ye, Y. Cui. An integrated 3D hydrophilicity/hydrophobicity design for artificial sweating skin (i-TRANS) mimicking human body perspiration. Adv Mater, 34 (44) (2022), p. e2204168.
[6]
M. Furtado, L. Chen, Z. Chen, A. Chen, W. Cui. Development of fish collagen in tissue regeneration and drug delivery. Eng Regener, 3 (3) (2022), pp. 217-231.
[7]
J. Mao, Q. Saiding, S. Qian, Z. Liu, B. Zhao, Q. Zhao, et al. Front cover: reprogramming stem cells in regenerative medicine (smart medicine 1/2022). Smart Med, 1 (1) (2022), p. e38.
[8]
P. Pleguezuelos-Beltrán, P. Gálvez-Martín, D. Nieto-García, J.A. Marchal, E. López-Ruiz. Advances in spray products for skin regeneration. Bioact Mater, 16 (2022), pp. 187-203.
[9]
J. Wang, D. Huang, H. Yu, Y. Cheng, H. Ren, Y. Zhao. Developing tissue engineering strategies for liver regeneration. Eng Regen, 3 (1) (2022), pp. 80-91.
[10]
Y. Gao, Q. Ma. Bacterial infection microenvironment-responsive porous microspheres by microfluidics for promoting anti-infective therapy. Smart Med, 1 (1) (2022), p. e20220012.
[11]
L. Fu, L. Li, Q. Bian, B. Xue, J. Jin, J. Li, et al. Cartilage-like protein hydrogels engineered via entanglement. Nature, 618 (7966) (2023), pp. 740-747.
[12]
C. Huang, L. Dong, B. Zhao, Y. Lu, S. Huang, Z. Yuan, et al. Anti-inflammatory hydrogel dressings and skin wound healing. Clin Transl Med, 12 (11) (2022), p. e1094.
[13]
J. Zhang, A.N. Keith, S.S. Sheiko, X. Wang, Z. Wang. To mimic mechanical properties of the skin by inducing oriented nanofiber microstructures in bottlebrush cellulose-graft-diblock copolymer elastomers. ACS Appl Mater Interfaces, 13 (2) (2021), pp. 3278-3286.
[14]
S.J. Mostafavi Yazdi, J. Baqersad. Mechanical modeling and characterization of human skin: a review. J Biomech, 130 (2022), Article 110864.
[15]
C. Norioka, Y. Inamoto, C. Hajime, A. Kawamura, T. Miyata. A universal method to easily design tough and stretchable hydrogels. NPG Asia Mater, 13 (1) (2021), p. 34.
[16]
H. Cao, L. Duan, Y. Zhang, J. Cao, K. Zhang. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal Transduct Target Ther, 6 (1) (2021), p. 426.
[17]
G. Zhang, J. Steck, J. Kim, C.H. Ahn, Z. Suo. Hydrogels of arrested phase separation simultaneously achieve high strength and low hysteresis. Sci Adv, 9 (26) (2023), p. eadh7742.
[18]
L. Li, K. Zhang, T. Wang, P. Wang, B. Xue, Y. Cao, et al. Biofabrication of a biomimetic supramolecular-polymer double network hydrogel for cartilage regeneration. Mater Des, 189 (2020), Article 108492.
[19]
Y. Meng, L. Chen, Y. Chen, J. Shi, Z. Zhang, Y. Wang, et al. Reactive metal boride nanoparticles trap lipopolysaccharide and peptidoglycan for bacteria-infected wound healing. Nat Commun, 13 (1) (2022), p. 7353.
[20]
T.H. Qazi, D.J. Mooney, G.N. Duda, S. Geissler. Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs. Biomaterials, 140 (2017), pp. 103-114.
[21]
X. Liu, J. Cao, H. Li, J. Li, Q. Jin, K. Ren, et al. Mussel-inspired polydopamine: a biocompatible and ultrastable coating for nanoparticles in vivo. ACS Nano, 7 (10) (2013), pp. 9384-9395.
[22]
S. Wan, X. Fu, Y. Ji, M. Li, X. Shi, Y. Wang. FAK- and YAP/TAZ dependent mechanotransduction pathways are required for enhanced immunomodulatory properties of adipose-derived mesenchymal stem cells induced by aligned fibrous scaffolds. Biomaterials, 171 (2018), pp. 107-117.
[23]
T. Li, H. Ma, H. Ma, Z. Ma, L. Qiang, Z. Yang, et al. Mussel-inspired nanostructures potentiate the immunomodulatory properties and angiogenesis of mesenchymal stem cells. ACS Appl Mater Interfaces, 11 (19) (2019), pp. 17134-17146.
[24]
C. Gao, C. Lu, Z. Jian, T. Zhang, Z. Chen, Q. Zhu, et al. 3D bioprinting for fabricating artificial skin tissue. Colloids Surf B Biointerfaces, 208 (2021), Article 112041.
[25]
S. Jiang, S.C. Li, C. Huang, B.P. Chan, Y. Du. Physical properties of implanted porous bioscaffolds regulate skin repair: focusing on mechanical and structural features. Adv Healthc Mater, 7 (6) (2018), p. e1700894.
[26]
L. Diaz-Gomez, I. Gonzalez-Prada, R. Millan, A. Da Silva-Candal, A. Bugallo-Casal, F. Campos, et al. 3D printed carboxymethyl cellulose scaffolds for autologous growth factors delivery in wound healing. Carbohydr Polym, 278 (2022), Article 118924.
[27]
L. Roshangar, J.S. Rad, R. Kheirjou, A.F. Khosroshahi. Using 3D-bioprinting scaffold loaded with adipose-derived stem cells to burns wound healing. J Tissue Eng Regen Med, 15 (6) (2021), pp. 546-555.
[28]
C. Niu, L. Wang, D. Ji, M. Ren, D. Ke, Q. Fu, et al. Fabrication of SA/Gel/C scaffold with 3D bioprinting to generate micro-nano porosity structure for skin wound healing: a detailed animal in vivo study. Cell Regen, 11 (1) (2022), p. 10.
[29]
B.S. Kim, G. Gao, J.Y. Kim, D.W. Cho. 3D cell printing of perfusable vascularized human skin equivalent composed of epidermis, dermis, and hypodermis for better structural recapitulation of native skin. Adv Healthc Mater, 8 (7) (2019), p. e1801019.
[30]
Y. Huyan, Q. Lian, T. Zhao, D. Li, J. He. Pilot study of the biological properties and vascularization of 3D printed bilayer skin grafts. Int J Bioprint, 6 (1) (2020), p. 246.
[31]
B.S. Kim, Y.W. Kwon, J.S. Kong, G.T. Park, G. Gao, W. Han, et al. 3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink: a step towards advanced skin tissue engineering. Biomaterials, 168 (2018), pp. 38-53.
[32]
D. Kang, Z. Liu, C. Qian, J. Huang, Y. Zhou, X. Mao, et al. 3D bioprinting of a gelatin-alginate hydrogel for tissue-engineered hair follicle regeneration. Acta Biomater, 165 (2023), pp. 19-30.
[33]
Y.C. Yung, J. Chae, M.J. Buehler, C.P. Hunter, D.J. Mooney. Cyclic tensile strain triggers a sequence of autocrine and paracrine signaling to regulate angiogenic sprouting in human vascular cells. Proc Natl Acad Sci USA, 106 (36) (2009), pp. 15279-15284.
[34]
B. Nedelec, H.A. Shankowsky, E.E. Tredget. Rating the resolving hypertrophic scar: comparison of the Vancouver Scar Scale and scar volume. J Burn Care Rehabil, 21 (3) (2000), pp. 205-212.
[35]
P. Patil, K.A. Russo, J.T. McCune, A.C. Pollins, M.A. Cottam, B.R. Dollinger, et al. Reactive oxygen species-degradable polythioketal urethane foam dressings to promote porcine skin wound repair. Sci Transl Med, 14 (641) (2022), p. eabm6586.
[36]
C. Luo, A. Guo, Y. Zhao, X. Sun. A high strength, low friction, and biocompatible hydrogel from PVA, chitosan and sodium alginate for articular cartilage. Carbohydr Polym, 286 (2022), Article 119268.
[37]
G. Sennakesavan, M. Mostakhdemin, L.K. Dkhar, A. Seyfoddin, S.J. Fatihhi. Acrylic acid/acrylamide based hydrogels and its properties—a review. Polym Degrad Stabil, 180 (2020), Article 109308.
[38]
S. Tang, L. Wang, Y. Zhang, F. Zhang. A biomimetic platelet-rich plasma-based interpenetrating network printable hydrogel for bone regeneration. Front Bioeng Biotechnol, 10 (2022), Article 887454.
[39]
L. Zhang, J. Zhao, J. Zhu, C. He, H. Wang. Anisotropic tough poly(vinyl alcohol) hydrogels. Soft Matter, 8 (40) (2012), pp. 10439-10447.
[40]
S. Mitragotri, J. Lahann. Physical approaches to biomaterial design. Nat Mater, 8 (1) (2009), pp. 15-23.
[41]
W. Li, Y. Liu, P. Zhang, Y. Tang, M. Zhou, W. Jiang, et al. Tissue-engineered bone immobilized with human adipose stem cells-derived exosomes promotes bone regeneration. ACS Appl Mater Interfaces, 10 (6) (2018), pp. 5240-5254.
[42]
Y. Long, Y. Niu, K. Liang, Y. Du. Mechanical communication in fibrosis progression. Trends Cell Biol, 32 (1) (2022), pp. 70-90.
[43]
M. D’Urso, N.A. Kurniawan. Mechanical and physical regulation of fibroblast-myofibroblast transition: from cellular mechanoresponse to tissue pathology. Front Bioeng Biotechnol, 8 (2020), Article 609653.
[44]
D.J. Tschumperlin, D. Lagares. Mechano-therapeutics: targeting mechanical signaling in fibrosis and tumor stroma. Pharmacol Ther, 212 (2020), Article 107575.
[45]
X. Wang, Y. Zhang, J. Luo, T. Xu, C. Si, A.J.C. Oscanoa, et al. Printability of hybridized composite from maleic acid-treated bacterial cellulose with gelatin for bone tissue regeneration. Adv Compos Hybrid Mater, 6 (4) (2023), p. 134.
[46]
D. Henn, K. Chen, T. Fehlmann, A.A. Trotsyuk, D. Sivaraj, Z.N. Maan, et al. Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2+ macrophages. Sci Adv, 7 (49) (2021), p. eabi4528.
[47]
L. Li, X. Liu, W. Tao, Y. Li, Y. Du, S. Zhang. Micropatterned composite membrane guides oriented cell growth and vascularization for accelerating wound healing. Regen Biomater, 10 (2022), p. rbac108.
[48]
A.V. Shinde, C. Humeres, N.G. Frangogiannis. The role of α-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling. Biochim Biophys Acta Mol Basis Dis, 1863 (1) (2017), pp. 298-309.
[49]
A. Putra, I. Alif, N. Hamra, O. Santosa, A.R. Kustiyah, A.M. Muhar, et al. MSC-released TGF-β regulate α-SMA expression of myofibroblast during wound healing. J Stem Cells Regen Med, 16 (2) (2020), pp. 73-79.
[50]
S. Chen, J. Yang, Y. Wei, X. Wei. Epigenetic regulation of macrophages: from homeostasis maintenance to host defense. Cell Mol Immunol, 17 (1) (2020), pp. 36-49.
[51]
T.G. Walsh, P. Metharom, M.C. Berndt. The functional role of platelets in the regulation of angiogenesis. Platelets, 26 (3) (2015), pp. 199-211.
[52]
J. Kisucka, C.E. Butterfield, D.G. Duda, S.C. Eichenberger, S. Saffaripour, J. Ware, et al. Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage. Proc Natl Acad Sci USA, 103 (4) (2006), pp. 855-860.
[53]
P. Carmeliet, R.K. Jain. Molecular mechanisms and clinical applications of angiogenesis. Nature, 473 (7347) (2011), pp. 298-307.
[54]
A.S. Leroyer, P.E. Rautou, J.S. Silvestre, Y. Castier, G. Lesèche, C. Devue, et al. CD 40 ligand+ microparticles from human atherosclerotic plaques stimulate endothelial proliferation and angiogenesis a potential mechanism for intraplaque neovascularization. J Am Coll Cardiol, 52 (16) (2008), pp. 1302-1311.
[55]
S.P. Herbert, D.Y. Stainier. Molecular control of endothelial cell behaviour during blood vessel morphogenesis. Nat Rev Mol Cell Biol, 12 (9) (2011), pp. 551-564.
[56]
M. Hellström, L.K. Phng, J.J. Hofmann, E. Wallgard, L. Coultas, P. Lindblom, et al. Dll 4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature, 445 (7129) (2007), pp. 776-780.
[57]
M. Rada, A. Kapelanski-Lamoureux, S. Petrillo, S. Tabariès, P. Siegel, A.R. Reynolds, et al. Runt related transcription factor-1 plays a central role in vessel co-option of colorectal cancer liver metastases. Commun Biol, 4 (1) (2021), p. 950.
[58]
J. Zhang, S. Fukuhara, K. Sako, T. Takenouchi, H. Kitani, T. Kume, et al. Angiopoietin-1/ Tie2 signal augments basal Notch signal controlling vascular quiescence by inducing delta-like 4 expression through AKT-mediated activation of beta-catenin. J Biol Chem, 286 (10) (2011), pp. 8055-8066.
[59]
Z. Wei, R. Schnellmann, H.C. Pruitt, S. Gerecht. Hydrogel network dynamics regulate vascular morphogenesis. Cell Stem Cell, 27 (5) (2020), pp. 798-812.e6.
[60]
S. Arlier, W. Murk, O. Guzeloglu-Kayisli, N. Semerci, K. Larsen, M.S. Tabak, et al. The extracellular signal-regulated kinase 1/ 2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation. AM J Reprod Immunol, 78 (6) (2017), p. e12760.
[61]
Y.H. Ma, S. Ling, H.E. Ives. Mechanical strain increases PDGF-B and PDGF beta receptor expression in vascular smooth muscle cells. Biochem Biophys Res Commun, 265 (2) (1999), pp. 606-610.
[62]
M. Ikeda, H. Kito, B.E. Sumpio. Phosphatidylinositol-3 kinase dependent MAP kinase activation via p21ras in endothelial cells exposed to cyclic strain. Biochem Biophys Res Commun, 257 (3) (1999), pp. 668-671.
[63]
H. Iwasaki, T. Yoshimoto, T. Sugiyama, Y. Hirata. Activation of cell adhesion kinase beta by mechanical stretch in vascular smooth muscle cells. Endocrinology, 144 (6) (2003), pp. 2304-2310.
[64]
B.A. Bryan, E. Dennstedt, D.C. Mitchell, T.E. Walshe, K. Noma, R. Loureiro, et al. RhoA/ROCK signaling is essential for multiple aspects of VEGF-mediated angiogenesis. FASEB J, 24 (9) (2010), pp. 3186-3195.
[65]
N. Takeshita, M. Hasegawa, K. Sasaki, D. Seki, M. Seiryu, S. Miyashita, et al. In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force. J Bone Miner Metab, 35 (1) (2017), pp. 40-51.
PDF(4096 KB)

Accesses

Citation

Detail

段落导航
相关文章

/