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Research Article

Enhanced cellular infiltration of tissue-engineered scaffolds fabricated by PLLA nanogrooved microfibers

Lei Zhan1,§Lingtian Wang2,§Jixia Deng1Yi Zheng1Qinfei Ke1Xinrui Yang3( )Xing Zhang3Weitao Jia2( )Chen Huang1( )
Engineering Research Center of Technical Textiles, Ministry of Education, College of Textiles, Donghua University, Shanghai 201620, China
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China

§ Lei Zhan and Lingtian Wang contributed equally to this work.

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Graphical Abstract

Inspired by the fact that pore size of fibrous architectures is always positively related to fiber diameter, we fabricated three-dimensional (3D) electrospun scaffolds composed of poly(L-lactic acid) (PLLA) microfibers with nanogrooves on fiber surface. The topographical cues from nanogrooves ensured fast cell adhesion, whilst the stable large pores formed by microfibers enabled sufficient cell ingrowth.

Abstract

Nanofibers prepared by electrospinning technique are extensively applied as building blocks for tissue-engineered scaffolds because of their high resemblance to natural extracellular matrix (ECM) and the capacity to provide more cell contacts than microfibers. However, conventional electrospun scaffolds only allow superficial growth of cells in that the size of inter-fiber pores is much smaller than the size of cells. By taking advantage of the positive correlation between fiber diameter and pore size in fibrous materials, we report here a simple method for fabricating poly-L-lactic acid (PLLA) microfiber scaffold with longitudinally aligned nanogrooves on fiber surface. Three-dimensional (3D) and structurally stable PLLA scaffolds with an average pore size of 16 μm were successfully acquired when the fiber diameter was 4.22 μm. The topographical cues from nanogrooves ensured fast cell adhesion of scaffolds, whilst the large inter-fiber pores enabled sufficient cell infiltration. Moreover, the nanogrooved microfiber scaffold showed improved curative effects of wound healing in a rat skin injury model, making us believe its practical significance in biomedical areas that requires fast cell adhesion and high cell infiltration.

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References

[1]

Weigel, T.; Malkmus, C.; Weigel, V.; Wußmann, M.; Berger, C.; Brennecke, J.; Groeber-Becker, F.; Hansmann, J. Fully synthetic 3D fibrous scaffolds for stromal tissues-replacement of animal-derived scaffold materials demonstrated by multilayered skin. Adv. Mater. 2022, 34, 2106780.

[2]

Zhang, B. L.; Shen, M. W.; Shi, X. Y. Preparation and biomedical applications of electrospun short fibers. J. Tex. Res. 2021, 42, 1–8.

[3]

Gao, X. Z., Han, S. Y., Zhang, R. H.; Liu, G. T.; Wu, J. Progress in electrospun composite nanofibers: Composition, performance and applications for tissue engineering. J. Mater. Chem. B 2019, 7, 7075–7089.

[4]

Jia, L.; Chen, L. N.; Zhang, H. X.; Qin, X. H. Performance of composite polyurethane/collagen nanofiber scaffolds. J. Tex. Res. 2016, 37, 1–6.

[5]

Wu, H. J.; Fan, J. T.; Chu, C. C.; Wu, J. Electrospinning of small diameter 3-D nanofibrous tubular scaffolds with controllable nanofiber orientations for vascular grafts. J. Mater. Sci. :Mater. Med. 2010, 21, 3207–3215.

[6]

Guo, Y. N.; Huang, J.; Fang, Y. F.; Huang, H.; Wu, J. 1D, 2D, and 3D scaffolds promoting angiogenesis for enhanced wound healing. Chem. Eng. J. 2022, 437, 134690.

[7]

Lu, J. J.; Sun, X.; Yin, H. Y.; Shen, X. Z.; Yang, S. H.; Wang, Y.; Jiang, W. L.; Sun, Y.; Zhao, L. Y.; Sun, X. D. et al. A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration. Nano Res. 2018, 11, 4599–4613.

[8]

Yan, Z. W.; Qian, Y.; Fan, C. Y. Biomimicry in 3D printing design: Implications for peripheral nerve regeneration. Regen. Med. 2021, 16, 683–701.

[9]

Zhou, Y.; Liu, G. T.; Huang, H.; Wu, J. Advances and impact of arginine-based materials in wound healing. J. Mater. Chem. B 2021, 9, 6738–6750.

[10]

Zouhair, S.; Aguiari, P.; Lop, L.; Vásquez-Rivera, A.; Filippi, A.; Romanato, F.; Korossis, S.; Wolkers, W. F.; Gerosa, G. Preservation strategies for decellularized pericardial scaffolds for off-the-shelf availability. Acta Biomater. 2019, 84, 208–221.

[11]

Wu, J. L.; Hong, Y. Enhancing cell infiltration of electrospun fibrous scaffolds in tissue regeneration. Bioact. Mater. 2016, 1, 56–64.

[12]

Wang, H. B.; Mullins, M. E.; Cregg, J. M.; McCarthy, C. W.; Gilbert, R. J. Varying the diameter of aligned electrospun fibers alters neurite outgrowth and Schwann cell migration. Acta Biomater. 2010, 6, 2970–2978.

[13]

Sisson, K.; Zhang, C.; Farach-Carson, M. C.; Chase, D. B.; Rabolt, J. F. Fiber diameters control osteoblastic cell migration and differentiation in electrospun gelatin. J. Biomed. Mater. Res. Part A 2010, 94A, 1312–1320.

[14]

Pham, Q. P.; Sharma, U.; Mikos, A. G. Electrospinning of polymeric nanofibers for tissue engineering applications: A review. Tissue Eng. 2006, 12, 1197–1211.

[15]

Mahjour, S. B.; Sefat, F.; Polunin, Y.; Wang, L. C.; Wang, H. J. Improved cell infiltration of electrospun nanofiber mats for layered tissue constructs. J. Biomed. Mater. Res. Part A 2016, 104, 1479–1488.

[16]

Loh, X. J.; Peh, P.; Liao, S. S.; Sng, C.; Li, J. Controlled drug release from biodegradable thermoresponsive physical hydrogel nanofibers. J. Control. Release 2010, 143, 175–182.

[17]

Blakeney, B. A.; Tambralli, A.; Anderson, J. M.; Andukuri, A.; Lim, D. J.; Dean, D. R.; Jun, H. W. Cell infiltration and growth in a low density, uncompressed three-dimensional electrospun nanofibrous scaffold. Biomaterials 2011, 32, 1583–1590.

[18]

Zhong, H. L.; Huang, J.; Wu, J.; Du, J. H. Electrospinning nanofibers to 1D, 2D, and 3D scaffolds and their biomedical applications. Nano Res. 2022, 15, 787–804.

[19]

Lei, C.; Cao, Y. X.; Hosseinpour, S.; Gao, F.; Liu, J. Y.; Fu, J. Y.; Staples, R.; Ivanovski, S.; Xu, C. Hierarchical dual-porous hydroxyapatite doped dendritic mesoporous silica nanoparticles based scaffolds promote osteogenesis in vitro and in vivo. Nano Res. 2021, 14, 770–777.

[20]

Baker, B. M.; Gee, A. O.; Metter, R. B.; Nathan, A. S.; Marklein, R. A.; Burdick, J. A.; Mauck, R. L. The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. Biomaterials 2008, 29, 2348–2358.

[21]

Jin, G.; Lee, S.; Kim, S. H.; Kim, M.; Jang, J. H. Bicomponent electrospinning to fabricate three-dimensional hydrogel-hybrid nanofibrous scaffolds with spatial fiber tortuosity. Biomed. Microdevices 2014, 16, 793–804.

[22]

Jin, G.; Shin, M.; Kim, S. H.; Lee, H.; Jang, J. H. SpONGE: Spontaneous organization of numerous-layer generation by electrospray. Angew. Chem., Int. Ed. 2015, 54, 7587–7591.

[23]

Li, Y.; Wang, J.; Qian, D. J.; Chen, L.; Mo, X. M.; Wang, L.; Wang, Y.; Cui, W. G. Electrospun fibrous sponge via short fiber for mimicking 3D ECM. J. Nanobiotechnol. 2021, 19, 131.

[24]

Xu, Z. J.; Liu, G. T.; Li, Q.; Wu, J. A novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity for enhanced diabetic wound repair. Nano Res. 2022, 15, 5305–5315.

[25]

Balguid, A.; Mol, A.; van Marion, M. H.; Bank, R. A.; Bouten, C. V. C.; Baaijens, F. P. T. Tailoring fiber diameter in electrospun poly(ɛ-caprolactone) scaffolds for optimal cellular infiltration in cardiovascular tissue engineering. Tissue Eng. Part A 2009, 15, 437–444.

[26]

Eichhorn, S. J.; Sampson, W. W. Statistical geometry of pores and statistics of porous nanofibrous assemblies. J. Roy. Soc. Interface 2005, 2, 309–318.

[27]

Hu, W. W.; Wu, Y. C.; Hu, Z. C. The development of an alginate/polycaprolactone composite scaffold for in situ transfection application. Carbohydr. Polym. 2018, 183, 29–36.

[28]

Zhao, S. C.; Li, L.; Wang, H.; Zhang, Y. D.; Cheng, X. G.; Zhou, N.; Rahaman, M. N.; Liu, Z. T.; Huang, W. H.; Zhang, C. Q. Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model. Biomaterials 2015, 53, 379–391.

[29]

Shanmugasundaram, O. L.; Ahmed, K. S. Z.; Sujatha, K.; Ponnmurugan, P.; Srivastava, A.; Ramesh, R.; Sukumar, R.; Elanithi, K. Fabrication and characterization of chicken feather keratin/polysaccharides blended polymer coated nonwoven dressing materials for wound healing applications. Mater. Sci. Eng. :C 2018, 92, 26–33.

[30]

Yang, H. J.; Ye, Q.; Zhou, Y. S.; Xiang, Y. L.; Xing, Q.; Dong, X.; Wang, D. J.; Xu, W. L. Formation, morphology and control of high-performance biomedical polyurethane porous membranes by water micro-droplet induced phase inversion. Polymer 2014, 55, 5500–5508.

[31]

Qian, Y.; Xu, Y.; Yan, Z. W.; Jin, Y.; Chen, X.; Yuan, W. E.; Fan, C. Y. Boron nitride nanosheets functionalized channel scaffold favors microenvironment rebalance cocktail therapy for piezocatalytic neuronal repair. Nano Energy 2021, 83, 105779.

[32]
Xian, C. H.; Zhang, Z.; You, X. R. , Fang, Y. F.; Wu, J. Nanosized fat emulsion injection modulating local microenvironment promotes angiogenesis in chronic wound healing. Adv. Funct. Mater., in press, https://doi.org/10.1002/adfm.202202410.
[33]

Barriga, E. H.; Franze, K.; Charras, G.; Mayor, R. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo. Nature 2018, 554, 523–527.

[34]

Ming, G. L.; Wong, S. T.; Henley, J.; Yuan, X. B.; Song, H. J.; Spitzer, N. C.; Poo, M. M. Adaptation in the chemotactic guidance of nerve growth cones. Nature 2002, 417, 411–418.

[35]

Ko, Y. G.; Co, C. C.; Ho, C. C. Directing cell migration in continuous microchannels by topographical amplification of natural directional persistence. Biomaterials 2013, 34, 353–360.

[36]

Bienert, M.; Hoss, M.; Bartneck, M.; Weinandy, S.; Böbel, M.; Jockenhövel, S.; Knüchel, R.; Pottbacker, K.; Wöltje, M.; Jahnen-Dechent, W. et al. Growth factor-functionalized silk membranes support wound healing in vitro. Biomed. Mater. 2017, 12, 045023.

[37]

Li, J.; Zhang, Y. P.; Kirsner, R. S. Angiogenesis in wound repair: Angiogenic growth factors and the extracellular matrix. Microsc. Res. Tech. 2003, 60, 107–114.

[38]

Schiffmann, L. M.; Werthenbach, J. P.; Heintges-Kleinhofer, F.; Seeger, J. M.; Fritsch, M.; Günther, S. D.; Willenborg, S.; Brodesser, S.; Lucas, C.; Jüngst, C. et al. Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth. Nat. Commun. 2020, 11, 3653.

[39]

Jiang, J.; Carlson, M. A.; Teusink, M. J.; Wang, H. J.; MacEwan, M. R.; Xie, J. W. Expanding two-dimensional electrospun nanofiber membranes in the third dimension by a modified gas-foaming technique. ACS Biomater. Sci. Eng. 2015, 1, 991–1001.

[40]

Kennedy, K. M.; Bhaw-Luximon, A.; Jhurry, D. Cell-matrix mechanical interaction in electrospun polymeric scaffolds for tissue engineering: Implications for scaffold design and performance. Acta Biomater. 2017, 50, 41–55.

[41]

Hochleitner, G.; Jüngst, T.; Brown, T. D.; Hahn, K.; Moseke, C.; Jakob, F.; Dalton, P. D.; Groll, J. Additive manufacturing of scaffolds with sub-micron filaments via melt electrospinning writing. Biofabrication 2015, 7, 035002.

[42]

Ekaputra, A. K.; Prestwich, G. D.; Cool, S. M.; Hutmacher, D. W. Combining electrospun scaffolds with electrosprayed hydrogels leads to three-dimensional cellularization of hybrid constructs. Biomacromolecules 2008, 9, 2097–2103.

[43]

Nam, J.; Huang, Y.; Agarwal, S.; Lannutti, J. Improved cellular infiltration in electrospun fiber via engineered porosity. Tissue Eng. 2007, 13, 2249–2257.

[44]

Kim, S. J.; Jang, D. H.; Park, W. H.; Min, B. M. Fabrication and characterization of 3-dimensional PLGA nanofiber/microfiber composite scaffolds. Polymer 2010, 51, 1320–1327.

[45]

Pham, Q. P.; Sharma, U.; Mikos, A. G. Electrospun poly(ɛ-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: Characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules 2006, 7, 2796–2805.

[46]

Zhu, Y. Z.; Liang, H.; Liu, X. M.; Wu, J.; Yang, C.; Wong, T. M.; Kwan, K. Y. H.; Cheung, K. M. C.; Wu, S. L.; Yeung, K. W. K. Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration. Sci. Adv. 2021, 7, eabf6654.

[47]

Chen, W. Q.; Villa-Diaz, L. G.; Sun, Y. B.; Weng, S. N.; Kim, J. K.; Lam, R. H. W.; Han, L.; Fan, R.; Krebsbach, P. H.; Fu, J. P. Nanotopography influences adhesion, spreading, and self-renewal of human embryonic stem cells. ACS Nano 2012, 6, 4094–4103.

[48]

Brydone, A. S.; Dalby, M. J.; Berry, C. C.; Meek, R. M. D.; McNamara, L. E. Grooved surface topography alters matrix-metalloproteinase production by human fibroblasts. Biomed. Mater. 2011, 6, 035005.

[49]

Kim, D. H.; Han, K.; Gupta, K.; Kwon, K. W.; Suh, K. Y.; Levchenko, A. Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients. Biomaterials 2009, 30, 5433–5444.

[50]

Kaiser, J. P.; Reinmann, A.; Bruinink, A. The effect of topographic characteristics on cell migration velocity. Biomaterials 2006, 27, 5230–5241.

[51]

Lim, J.; Choi, A.; Kim, H. W.; Yoon, H.; Park, S. M.; Tsai, C. H. D.; Kaneko, M.; Kim, D. S. Constrained adherable area of nanotopographic surfaces promotes cell migration through the regulation of focal adhesion via focal adhesion kinase/Rac1 activation. ACS Appl. Mater. Interfaces 2018, 10, 14331–14341.

[52]

Shin, J. Y.; Kim, H. N.; Bhang, S. H.; Yoon, J. K.; Suh, K. Y.; Jeon, N. L.; Kim, B. S. Topography-guided control of local migratory behaviors and protein expression of cancer cells. Adv. Healthc. Mater. 2017, 6, 1700155.

[53]

Zhan, L.; Deng, J. X.; Ke, Q. F.; Li, X.; Ouyang, Y. M.; Huang, C.; Liu, X. Q.; Qian, Y. Grooved fibers: Preparation principles through electrospinning and potential applications. Adv. Fiber Mater. 2022, 4, 203–213.

[54]

Chen, X.; Xu, Y.; Zhang, W. X.; Xu, K. L.; Ke, Q. F.; Jin, X. Y.; Huang, C. Online fabrication of ultralight, three-dimensional, and structurally stable ultrafine fibre assemblies with a double-porous feature. Nanoscale 2019, 11, 8185–8195.

[55]

Liang, M. M.; Chen, X.; Xu, Y.; Zhu, L.; Jin, X. Y.; Huang, C. Double-grooved nanofibre surfaces with enhanced anisotropic hydrophobicity. Nanoscale 2017, 9, 16214–16222.

[56]

Huang, C.; Ouyang, Y. M; Niu, H. T.; He, N. F.; Ke, Q. F.; Jin, X. Y.; Li, D. W.; Fang, J.; Liu, W. J.; Fan, C. Y. et al. Nerve guidance conduits from aligned nanofibers: Improvement of nerve regeneration through longitudinal nanogrooves on a fiber surface. ACS Appl. Mater. Interfaces 2015, 7, 7189–7196.

[57]

Supaphol, P.; Mit-Uppatham, C.; Nithitanakul, M. Ultrafine electrospun polyamide-6 fibers: Effect of emitting electrode polarity on morphology and average fiber diameter. J. Polym. Sci. Part B: Polym. Phys. 2005, 43, 3699–3712.

[58]

Huang, C.; Tang, Y. W.; Liu, X.; Sutti, A.; Ke, Q. F.; Mo, X. M.; Wang, X. G.; Morsi, Y.; Lin, T. Electrospinning of nanofibres with parallel line surface texture for improvement of nerve cell growth. Soft Matter 2011, 7, 10812–10817.

[59]

Gao, Q.; Gu, H. B.; Zhao, P.; Zhang, C. M.; Cao, M. Y.; Fu, J. Z.; He, Y. Fabrication of electrospun nanofibrous scaffolds with 3D controllable geometric shapes. Mater. Des. 2018, 157, 159–169.

[60]

Taskin, M. B.; Xia, D.; Besenbacher, F.; Dong, M. D.; Chen, M. L. Nanotopography featured polycaprolactone/polyethyleneoxide microfibers modulate endothelial cell response. Nanoscale 2017, 9, 9218–9229.

[61]

Badami, A. S.; Kreke, M. R.; Thompson, M. S.; Riffle, J. S.; Goldstein, A. S. Effect of fiber diameter on spreading, proliferation, and differentiation of osteoblastic cells on electrospun poly(lactic acid) substrates. Biomaterials 2006, 27, 596–606.

[62]

Zhang, Y. Z.; Ouyang, H. W.; Lim, C. T.; Ramakrishna, S.; Huang, Z. M. Electrospinning of gelatin fibers and gelatin/PCL composite fibrous scaffolds. J. Biomed. Mater. Res. Part B: Appl. Biomater. 2005, 72B, 156–165.

[63]

Sharma, P.; Ng, C.; Jana, A.; Padhi, A.; Szymanski, P.; Lee, J. S. H.; Behkam, B.; Nain, A. S. Aligned fibers direct collective cell migration to engineer closing and nonclosing wound gaps. Mol. Biol. Cell 2017, 28, 2579–2588.

[64]

Fong, E.; Tzlil, S.; Tirrell, D. A. Boundary crossing in epithelial wound healing. Proc. Natl. Acad. Sci. USA 2010, 107, 19302–19307.

[65]

Mak, K. M.; Png, C. Y. M.; Lee, D. J. Type V collagen in health, disease, and fibrosis. Anat. Rec. 2016, 299, 613–629.

[66]

Peterson, L. W.; Artis, D. Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 2014, 14, 141–153.

[67]

Yang, W. S.; Roh, H. W.; Lee, W. K.; Ryu, G. H. Evaluation of functions and tissue compatibility of poly (D,L-lactic-co-glycolic acid) seeded with human dermal fibroblasts. J. Biomater. Sci., Polym. Ed. 2006, 17, 151–162.

[68]

Wang, L.; Li, G. Y.; Ren, L.; Kong, X. D.; Wang, Y. G.; Han, X. G.; Jiang, W. B.; Dai, K. R.; Yang, K.; Hao, Y. Q. Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process. Int. J. Nanomedicine 2017, 12, 8443–8457.

[69]

Strunck, J. L.; Cutler, B.; Latour, E.; Seminario-Vidal, L.; Ortega-Loayza, A. G. Wound care dressings for pyoderma gangrenosum. J. Am. Acad. Dermatol. 2022, 86, 458–460.

[70]

Liu, X.; Lin, T.; Fang, J.; Yao, G.; Zhao, H. Q.; Dodson, M.; Wang, X. G. In vivo wound healing and antibacterial performances of electrospun nanofibre membranes. J. Biomed. Mater. Res. Part A 2010, 94A, 499–508.

[71]

Guimarães, A.; Martins, A.; Pinho, E. D.; Faria, S.; Reis, R. L.; Neves, N. M. Solving cell infiltration limitations of electrospun nanofiber meshes for tissue engineering applications. Nanomedicine 2010, 5, 539–554.

[72]

Hwang, P. T. J.; Murdock, K.; Alexander, G. C.; Salaam, A. D.; Ng, J. I.; Lim, D. J.; Dean, D.; Jun, H. W. Poly(ɛ-caprolactone)/gelatin composite electrospun scaffolds with porous crater-like structures for tissue engineering. J. Biomed. Mater. Res. Part A 2016, 104, 1017–1029.

[73]

Pal, P.; Srivas, P. K.; Dadhich, P.; Das, B.; Maulik, D.; Dhara, S. Nano-/microfibrous cotton-wool-like 3D scaffold with core–shell architecture by emulsion electrospinning for skin tissue regeneration. ACS Biomater. Sci. Eng. 2017, 3, 3563–3575.

[74]

Magrofuoco, E.; Flaibani, M.; Giomo, M.; Elvassore, N. Cell culture distribution in a three-dimensional porous scaffold in perfusion bioreactor. Biochem. Eng. J. 2019, 146, 10–19.

Nano Research
Pages 1614-1625
Cite this article:
Zhan L, Wang L, Deng J, et al. Enhanced cellular infiltration of tissue-engineered scaffolds fabricated by PLLA nanogrooved microfibers. Nano Research, 2023, 16(1): 1614-1625. https://doi.org/10.1007/s12274-022-4838-9
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Received: 16 June 2022
Revised: 26 July 2022
Accepted: 30 July 2022
Published: 26 August 2022
© Tsinghua University Press 2022
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