用于实时皮肤创面愈合的超强工程化蛋白凝聚体黏合剂

李铭, 柳柏梅, 徐炜, 赵来, 王自立, 何浩男, 李敬敬, 王帆, 马超, 刘凯, 张洪杰

工程（英文） ›› 2023, Vol. 31 ›› Issue (12) : 76-85.

PDF(2937 KB)
PDF(2937 KB)
工程（英文） ›› 2023, Vol. 31 ›› Issue (12) : 76-85. DOI: 10.1016/j.eng.2023.07.013
研究论文
Article

用于实时皮肤创面愈合的超强工程化蛋白凝聚体黏合剂

作者信息 +

Engineering Protein Coacervates into a Robust Adhesive for Real-Time Skin Healing

Author information +
History +

摘要

黏合剂作为生物医学工程中的一种先进方式，因其独特的伤口管理行为而备受关注。然而，由于当前的黏合剂系统界面粘合强度较弱，要实现牢固的黏合仍是一项巨大的挑战。此外，传统化学黏合剂缺乏动态适应性，限制了伤口周围的新生细胞向该部分迁移，导致组织再生效果不佳。在此，我们精心设计了一种具有强大黏附力和实时促皮肤愈合效果的细胞外基质衍生的生物复合黏合剂。在嵌合蛋白和天然DNA间超分子相互作用的积极参与下，液-液相分离被很好地用来驱动生物复合黏合剂的组装，从而获得增强的黏合性能。该生物黏合剂具有出色的黏合和止血性能，其中，剪切黏合强度约18 MPa，优于已报道的同类产品。此外，工程生物衍生成分赋予了该黏合材料优异的生物相容性和特殊的生物学功能，包括促进细胞增殖和迁移，因此使用这种材料最终可实现实时原位皮肤再生。这项工作为功能化生物黏合剂工程和生物医学转化开辟了新的途径。

Abstract

Adhesives have attracted a great deal of attention as an advanced modality in biomedical engineering because of their unique wound management behavior. However, it is a grand challenge for current adhesive systems to achieve robust adhesion due to their tenuous interfacial bonding strength. Moreover, the absence of dynamic adaptability in conventional chemical adhesives restricts neoblasts around the wound from migrating to the site, resulting in an inferior tissue-regeneration effect. Herein, an extracellular matrix-derived biocomposite adhesive with robust adhesion and a real-time skin healing effect is well-engineered. Liquid-liquid phase separation is well-harnessed to drive the assembly of the biocomposite adhesive, with the active involvement of supramolecular interactions between chimeric protein and natural DNA, leading to a robustly reinforced adhesion performance. The bioadhesive exhibits outstanding adhesion and sealing behaviors, with a sheared adhesion strength of approximately 18 MPa, outperforming its reported counterparts. Moreover, the engineered bioderived components endow this adhesive material with biocompatibility and exceptional biological functions including the promotion of cell proliferation and migration, such that the use of this material eventually yields real-time in situ skin regeneration. This work opens up novel avenues for functionalized bioadhesive engineering and biomedical translations.

关键词

生物复合黏合剂 / 蛋白 / DNA / 凝聚物 / 皮肤愈合

Keywords

Biocomposite adhesive / Protein / DNA / Coacervates / Skin healing

引用本文

EndNote

Ris (Procite)

Bibtex

导出引用
李铭, 柳柏梅, 徐炜. 用于实时皮肤创面愈合的超强工程化蛋白凝聚体黏合剂. Engineering. 2023, 31(12): 76-85 https://doi.org/10.1016/j.eng.2023.07.013

参考文献

原文顺序 | 文献年度倒序 | 文中引用次数倒序
[1]
G.M. Taboada, K. Yang, M.J.N. Pereira, S.S. Liu, Y. Hu, J.M. Karp, et al.. Overcoming the translational barriers of tissue adhesives. Nat Rev Mater, 5 (4) ( 2020), pp. 310-329 DOI: 10.1038/s41578-019-0171-7
[2]
J. Zhu, Q. Jin, H. Zhao, W. Zhu, Z. Liu, Q. Chen. Reactive oxygen species scavenging sutures for enhanced wound sealing and repair. Small Struct, 2 (7) ( 2021), Article 2100002
[3]
J. Ouyang, X. Ji, X. Zhang, C. Feng, Z. Tang, N. Kong, et al.. In situ sprayed NIR-responsive, analgesic black phosphorus-based gel for diabetic ulcer treatment. Proc Natl Acad Sci USA, 117 (46) ( 2020), pp. 28667-28677 DOI: 10.1073/pnas.2016268117
[4]
X. Chen, J. Zhang, G. Chen, Y. Xue, J. Zhang, X. Liang, et al.. Hydrogel bioadhesives with extreme acid-tolerance for gastric perforation repairing. Adv Funct Mater, 32 (29) ( 2022), Article 2202285
[5]
E. Shirzaei Sani, A. Kheirkhah, D. Rana, Z. Sun, W. Foulsham, A. Sheikhi, et al.. Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels. Sci Adv, 5 (3) ( 2019), Article eaav1281
[6]
S. Nam, D. Mooney. Polymeric tissue adhesives. Chem Rev, 121 (18) ( 2021), pp. 11336-11384 DOI: 10.1021/acs.chemrev.0c00798
[7]
R. Pinnaratip, M.S.A. Bhuiyan, K. Meyers, R.M. Rajachar, B.P. Lee. Multifunctional biomedical adhesives. Adv Healthc Mater, 8 (11) ( 2019), Article 1801568
[8]
S. Balcioglu, C. Gurses, I. Ozcan, A. Yildiz, S. Koytepe, H. Parlakpinar, et al.. Photocrosslinkable gelatin/collagen based bioinspired polyurethane-acrylate bone adhesives with biocompatibility and biodegradability. Int J Biol Macromol, 192 ( 2021), pp. 1344-1356
[9]
J. Gao, X. Yu, X. Wang, Y. He, J. Ding. Biomaterial-related cell microenvironment in tissue engineering and regenerative medicine. Engineering, 13 ( 2022), pp. 31-45
CrossRef ADS Google scholar
[10]
C. Feng, J. Ouyang, Z. Tang, N. Kong, Y. Liu, L. Fu, et al.. Germanene-based theranostic materials for surgical adjuvant treatment: inhibiting tumor recurrence and wound infection. Matter, 3 (1) ( 2020), pp. 127-144
[11]
X. Wang, M. Tang. Bioceramic materials with ion-mediated multifunctionality for wound healing. Smart Med, 1 (1) ( 2022), Article e20220032
[12]
A. Bal-Ozturk, B. Cecen, M. Avci-Adali, S.N. Topkaya, E. Alarcin, G. Yasayan, et al.. Tissue adhesives: from research to clinical translation. Nano Today, 36 ( 2021), Article 101049
[13]
P.J.M. Bouten, M. Zonjee, J. Bender, S.T.K. Yauw, H. Van Goor, J.C.M. Van Hest, et al.. The chemistry of tissue adhesive materials. Prog Polym Sci, 39 (7) ( 2014), pp. 1375-1405
[14]
A.H. Hofman, I.A. Van Hees, J. Yang, M. Kamperman. Bioinspired underwater adhesives by using the supramolecular toolbox. Adv Mater, 30 (19) ( 2018), Article 1704640
[15]
Q. Zhao, D.W. Lee, B.K. Ahn, S. Seo, Y. Kaufman, J.N. Israelachvili, et al.. Underwater contact adhesion and microarchitecture in polyelectrolyte complexes actuated by solvent exchange. Nat Mater, 15 (4) ( 2016), pp. 407-412 DOI: 10.1038/nmat4539
[16]
J. Sun, J. Chen, K. Liu, H. Zeng. Mechanically strong proteinaceous fibers: engineered fabrication by microfluidics. Engineering, 7 (5) ( 2021), pp. 615-623
[17]
R. Chang, X. Yan. Supramolecular immunotherapy of cancer based on the self-assembling peptide design. Small Struct, 1 (2) ( 2020), Article 2000068
[18]
B. Wang, H. Chen, T. Liu, S. Shi, T.P. Russell. Host-guest molecular recognition at liquid-liquid interfaces. Engineering, 7 (5) ( 2021), pp. 603-614
[19]
J. Sun, J. Zhang, L. Zhao, S. Wan, B. Wu, C. Ma, et al.. Contribution of hydrogen-bond nanoarchitectonics to switchable photothermal-mechanical properties of bioinorganic fibers. CCS Chem, 5 (5) ( 2023), pp. 1242-1250 DOI: 10.31635/ccschem.022.202201946
[20]
J. Li, Y. Sun, Y. Liang, J. Ma, B. Li, C. Ma, et al.. Extracellular elastin molecule modulates Alzheimer’s aβ dynamics in vitro and in vivo by affecting microglial activities. CCS Chem, 3 (7) ( 2021), pp. 1830-1837 DOI: 10.31635/ccschem.020.202000330
[21]
J. Sun, J. Han, F. Wang, K. Liu, H. Zhang. Bioengineered protein-based adhesives for biomedical applications. Chemistry, 28 (1) ( 2022), Article e202102902
[22]
C. Ma, J. Sun, B. Li, Y. Feng, Y. Sun, L. Xiang, et al.. Ultra-strong bio-glue from genetically engineered polypeptides. Nat Commun, 12 (1) ( 2021), p. 3613
[23]
M.J. Brennan, B.F. Kilbride, J.J. Wilker, J.C. Liu. A bioinspired elastin-based protein for a cytocompatible underwater adhesive. Biomaterials, 124 ( 2017), pp. 116-125
[24]
J. Su, B. Liu, H. He, C. Ma, B. Wei, M. Li, et al.. Engineering high strength and super-toughness of unfolded structural proteins and their extraordinary anti-adhesion performance for abdominal hernia repair. Adv Mater, 34 (19) ( 2022), Article 2200842
[25]
Z. Wei, J. Sun, S. Lu, Y. Liu, B. Wang, L. Zhao, et al.. An engineered protein-Au bioplaster for efficient skin tumor therapy. Adv Mater, 34 (16) ( 2022), Article 2110062
[26]
Z. Zhang, J. Zhou, C. Liu, J. Zhang, Y. Shibata, N. Kong, et al.. Emerging biomimetic nanotechnology in orthopedic diseases: progress, challenges, and opportunities. Trends Chem, 4 (5) ( 2022), pp. 420-436
[27]
J. Zhou, Z. Zhang, J. Joseph, X. Zhang, B.E. Ferdows, D.N. Patel, et al.. Biomaterials and nanomedicine for bone regeneration: progress and future prospects. Exploration, 1 (2) ( 2021), Article 20210011
[28]
X. Zhang, L. Li, J. Ouyang, L. Zhang, J. Xue, H. Zhang, et al.. Electroactive electrospun nanofibers for tissue engineering. Nano Today, 39 ( 2021), Article 101196
[29]
L. Li, X. Zhang, J. Zhou, L. Zhang, J. Xue, W. Tao, et al.. Non-invasive thermal therapy for tissue engineering and regenerative medicine. Small, 18 (36) ( 2022), Article 2107705
[30]
Shan J, Che J, Song C, Zhao Y. Emerging antibacterial nanozymes for wound healing. Smart Med 2023; 2(3):e20220025.
[31]
Y. Ren, Y. Zhang, Y. Liu, Q. Wu, H.G. Hu, J. Li, et al.. Highly reliable and efficient encoding systems for hexadecimal polypeptide-based data storage. Fundam Res, 3 (2) ( 2023), pp. 298-304 DOI: 10.3390/math11020298
[32]
H. Kim, W.H. Kong, K.Y. Seong, D.K. Sung, H. Jeong, J.K. Kim, et al.. Hyaluronate-epidermal growth factor conjugate for skin wound healing and regeneration. Biomacromolecules, 17 (11) ( 2016), pp. 3694-3705
[33]
M. Shao, Y. Fan, K. Zhang, Y. Hu, F.J. Xu. One nanosystem with potent antibacterial and gene-delivery performances accelerates infected wound healing. Nano Today, 39 ( 2021), Article 101224
[34]
W. Zhao, Y. Li, X. Zhang, R. Zhang, Y. Hu, C. Boyer, et al.. Photo-responsive supramolecular hyaluronic acid hydrogels for accelerated wound healing. J Control Release, 323 ( 2020), pp. 24-35
[35]
J. Sun, L. Xiao, B. Li, K. Zhao, Z. Wang, Y. Zhou, et al.. Genetically engineered polypeptide adhesive coacervates for surgical applications. Angew Chem Int Ed, 60 (44) ( 2021), pp. 23687-23694 DOI: 10.1002/anie.202100064
[36]
S. Wan, W. Cheng, J. Li, F. Wang, X. Xing, J. Sun, et al.. Biological composite fibers with extraordinary mechanical strength and toughness mediated by multiple intermolecular interacting networks. Nano Res, 15 (10) ( 2022), pp. 9192-9198 DOI: 10.1007/s12274-022-4595-9
[37]
L. Xiao, Z. Wang, Y. Sun, B. Li, B. Wu, C. Ma, et al.. An artificial phase-transitional underwater bioglue with robust and switchable adhesion performance. Angew Chem Int Ed, 60 (21) ( 2021), pp. 12082-12089
CrossRef ADS Google scholar
[38]
J. Li, A.D. Celiz, J. Yang, Q. Yang, I. Wamala, W. Whyte, et al.. Tough adhesives for diverse wet surfaces. Science, 357 ( 2017), pp. 378-381 DOI: 10.1126/science.aah6362
[39]
S. Xi, F. Tian, G. Wei, X. He, Y. Shang, Y. Ju, et al.. Reversible dendritic-crystal-reinforced polymer gel for bioinspired adaptable adhesive. Adv Mater, 33 (40) ( 2021), Article 2103174
[40]
T.I. Harris, D.A. Gaztambide, B.A. Day, C.L. Brock, A.L. Ruben, J.A. Jones, et al.. Sticky situation: an investigation of robust aqueous-based recombinant spider silk protein coatings and adhesives. Biomacromolecules, 17 (11) ( 2016), pp. 3761-3772 DOI: 10.1021/acs.biomac.6b01267
[41]
N. Annabi, Y.N. Zhang, A. Assmann, E.S. Sani, G. Cheng, A.D. Lassaletta, et al.. Engineering a highly elastic human protein-based sealant for surgical applications. Sci Transl Med, 9 (410) ( 2017), Article eaai7466
[42]
D. Zhang, Z. Xu, H. Li, C. Fan, C. Cui, T. Wu, et al.. Fabrication of strong hydrogen-bonding induced coacervate adhesive hydrogels with antibacterial and hemostatic activities. Biomater Sci, 8 (5) ( 2020), pp. 1455-1463 DOI: 10.1039/c9bm02029b
[43]
Q. Zhang, C.Y. Shi, D.H. Qu, Y.T. Long, B.L. Feringa, H. Tian. Exploring a naturally tailored small molecule for stretchable, self-healing, and adhesive supramolecular polymers. Sci Adv, 4 (7) ( 2018), Article eaat8192
[44]
J. Xu, X. Li, J. Li, X. Li, B. Li, Y. Wang, et al.. Wet and functional adhesives from one-step aqueous self-assembly of natural amino acids and polyoxometalates. Angew Chem Int Ed, 56 (30) ( 2017), pp. 8731-8735 DOI: 10.1002/anie.201703774
[45]
W.R. Wonderly, T.R. Cristiani, K.C. Cunha, G.D. Degen, J.E. Shea, J.H. Waite. Dueling backbones: comparing peptoid and peptide analogues of a mussel adhesive protein. Macromolecules, 53 (16) ( 2020), pp. 6767-6779 DOI: 10.1021/acs.macromol.9b02715
[46]
X. Liu, Q. Zhang, Z. Gao, R. Hou, G. Gao. Bioinspired adhesive hydrogel driven by adenine and thymine. ACS Appl Mater Interfaces, 9 (20) ( 2017), pp. 17645-17652 DOI: 10.1021/acsami.7b04832
[47]
Z. Meng, Q. Liu, Y. Zhang, J. Sun, C. Yang, H. Li, et al.. Highly stiff and stretchable DNA liquid crystalline organogels with super plasticity, ultrafast self-healing, and magnetic response behaviors. Adv Mater, 34 (3) ( 2022), Article 2106208
[48]
F. Li, J. Tang, J. Geng, D. Luo, D. Yang. Polymeric DNA hydrogel: design, synthesis and applications. Prog Polym Sci, 98 ( 2019), Article 101163
[49]
X. Zhao, Y. Liang, Y. Huang, J. He, Y. Han, B. Guo. Physical double-network hydrogel adhesives with rapid shape adaptability, fast self-healing, antioxidant and NIR/pH stimulus-responsiveness for multidrug-resistant bacterial infection and removable wound dressing. Adv Funct Mater, 30 (17) ( 2020), Article 1910748
[50]
W. Chen, R. Wang, T. Xu, X. Ma, Z. Yao, B. Chi, et al.. A mussel-inspired poly(γ-glutamic acid) tissue adhesive with high wet strength for wound closure. J Mater Chem B, 5 (28) ( 2017), pp. 5668-5678
[51]
X. Pei, H. Zhang, Y. Zhou, L. Zhou, J. Fu. Stretchable, self-healing and tissue-adhesive zwitterionic hydrogels as strain sensors for wireless monitoring of organ motions. Mater Horiz, 7 (7) ( 2020), pp. 1872-1882 DOI: 10.1039/d0mh00361a
[52]
H. Fan, J.P. Gong. Bioinspired underwater adhesives. Adv Mater, 33 (44) ( 2021), Article 2102983
[53]
W. Wei, Y. Tan, N.R. Martinez Rodriguez, J. Yu, J.N. Israelachvili, J.H. Waite. A mussel-derived one component adhesive coacervate. Acta Biomater, 10 (4) ( 2014), pp. 1663-1670
[54]
E. Filippidi, T.R. Cristiani, C.D. Eisenbach, J.H. Waite, J.N. Israelachvili, B.K. Ahn, et al.. Toughening elastomers using mussel-inspired iron-catechol complexes. Science, 358 ( 2017), pp. 502-505 DOI: 10.1126/science.aao0350
[55]
Lang N, Pereira MJ, Lee Y, Friehs I, Vasilyev NV, Feins EN, et al. A blood-resistant surgical glue for minimally invasive repair of vessels and heart defects. Sci Transl Med 2014; 6(218):218ra6.
[56]
J.K. Choi, J.H. Jang, W.H. Jang, J. Kim, I.H. Bae, J. Bae, et al.. The effect of epidermal growth factor (EGF) conjugated with low-molecular-weight protamine (LMWP) on wound healing of the skin. Biomaterials, 33 (33) ( 2012), pp. 8579-8590
[57]
Y. Xi, J. Ge, Y. Guo, B. Lei, P.X. Ma. Biomimetic elastomeric polypeptide-based nanofibrous matrix for overcoming multidrug-resistant bacteria and enhancing full-thickness wound healing/skin regeneration. ACS Nano, 12 (11) ( 2018), pp. 10772-10784 DOI: 10.1021/acsnano.8b01152
[58]
B. Hu, M. Gao, K.O. Boakye-Yiadom, W. Ho, W. Yu, X. Xu, et al.. An intrinsically bioactive hydrogel with on-demand drug release behaviors for diabetic wound healing. Bioact Mater, 6 (12) ( 2021), pp. 4592-4606
[59]
X. Peng, Y. Li, T. Li, Y. Li, Y. Deng, X. Xie, et al.. Coacervate-derived hydrogel with effective water repulsion and robust underwater bioadhesion promotes wound healing. Adv Sci, 9 (31) ( 2022), Article 2203890
[60]
Q. Peng, J. Chen, Z. Zeng, T. Wang, L. Xiang, X. Peng, et al.. Adhesive coacervates driven by hydrogen-bonding interaction. Small, 16 (43) ( 2020), Article 2004132
[61]
J. Koehler, F.P. Brandl, A.M. Goepferich. Hydrogel wound dressings for bioactive treatment of acute and chronic wounds. Eur Polym J, 100 ( 2018), pp. 1-11
[62]
R. Ying, W.C. Huang, X. Mao. Synthesis of agarose-based multistimuli-responsive hydrogel dressing for accelerated wound healing. ACS Biomater Sci Eng, 8 (1) ( 2022), pp. 293-302 DOI: 10.1021/acsbiomaterials.1c01215
[63]
F. Jiang, Z. Chi, Y. Ding, M. Quan, Y. Tian, J. Shi, et al.. Wound dressing hydrogel of Enteromorpha prolifera polysaccharide-polyacrylamide composite: a facile transformation of marine blooming into biomedical material. ACS Appl Mater Interfaces, 13 (12) ( 2021), pp. 14530-14542 DOI: 10.1021/acsami.0c21543
PDF(2937 KB)

Accesses

Citation

Detail
段落导航
相关文章

/

〈 〉