Subscriber access provided by READING UNIV
Article
Autonomously Self-Adhesive Hydrogels as Building Blocks for Additive Manufacturing Xudong Deng, Rana Attalla, Lukas P. Sadowski, Mengsu Chen, Michael J. Majcher, Ivan Urosev, Da-Chuan Yin, P. Ravi Selvaganapathy, Carlos D.M. Filipe, and Todd Hoare Biomacromolecules, Just Accepted Manuscript • DOI: 10.1021/acs.biomac.7b01243 • Publication Date (Web): 23 Nov 2017 Downloaded from http://pubs.acs.org on November 24, 2017
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Biomacromolecules is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
Autonomously Self-Adhesive Hydrogels as Building Blocks for Additive Manufacturing Xudong Deng,†,‡ Rana Attalla,§ Lukas P. Sadowski,‡ Mengsu Chen,‡ Michael J. Majcher,‡ Ivan Urosev,‡ Da-Chuan Yin,† P. Ravi Selvaganapathy,§ Carlos D. M. Filipe,*,‡ and Todd Hoare*,‡ †
Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences,
Northwestern Polytechnical University, Xi’an, 710072, P. R. China ‡
Department of Chemical Engineering and §Department of Mechanical Engineering, McMaster
University, 1280 Main Street West, Hamilton, ON, L8S 4L7, Canada
* To whom correspondence should be addressed:
[email protected];
[email protected] 1 ACS Paragon Plus Environment
Biomacromolecules 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
ABSTRACT
We report a simple method of preparing autonomous and rapid self-adhesive hydrogels and their use as building blocks for additive manufacturing of functional tissue scaffolds. Dynamic crosslinking between 2-aminophenylboronic acid-functionalized hyaluronic acid and poly(vinyl alcohol) yields hydrogels that recover their mechanical integrity within one minute after cutting or shear under both neutral and acidic pH conditions. Incorporation of this hydrogel in an interpenetrating calcium-alginate network results in an interfacially stiffer but still rapidly selfadhesive hydrogel that can be assembled into hollow perfusion channels by simple contact additive manufacturing within minutes. Such channels withstand fluid perfusion while retaining their dimensions and support endothelial cell growth and proliferation, providing a simple and modular route to produce customized cell scaffolds.
Keywords: self-healing hydrogels, additive manufacturing, endothelialization, cell scaffolds, interpenetrating network hydrogels
2 ACS Paragon Plus Environment
Page 2 of 28
Page 3 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
INTRODUCTION Hydrogels prepared using dynamic chemistries that facilitate continuous formation and degradation of crosslinks offer unique opportunities to apply hydrogels in non-traditional ways.1,2 A variety of dynamic crosslinking chemistries has been developed in recent years by multiple groups3-5 (including ours6,7) to facilitate both injectable delivery (via in situ gelation) as well as potential self-healing or self-adhesion following damage or fracture.8 Such hydrogels offer significant advantages in drug delivery,9 anti-biofouling materials,10 and mimicking the dynamic extracellular matrix.11 However, most self-healing or self-adhesive approaches based on covalent crosslinking require external stimuli or energy input, significantly limiting their applicability in vivo. As such, developing gel chemistries that can rapidly and autonomously selfadhere under physiological conditions offers potential to more effectively translate the promise of self-adhesive hydrogels into clinical applications.12-14 This is particularly true if self-adhesive approaches are to be used together with additive manufacturing to build complex biomedical devices such as 3D vascularized tissue scaffolds,15,16 an application in which maintaining high cell adhesion and viability during processing is essential. Methods to achieve functional vascularization within hydrogels include needle-based subtractive prevascularization17 or 3D printing of a dissolvable prevascular network of sacrificial materials.18,19 These methods need at least one additional step to remove the sacrificial material from the hydrogel. Furthermore, indirect 3D printing of a prevascular structure into hydrogels has to date required deposition of the precursor ink within a sacrificial support scaffold;20 direct template-free 3D printing of hollow channel structures remains difficult to realize.21,22 Layer-bylayer additive strategies to form prevascular hollow structures have been demonstrated but are slow, requiring at least a one-hour chemical sealing step to adhere the pre-channel structures.23,24
3 ACS Paragon Plus Environment
Biomacromolecules 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Rapid and autonomously self-adhesive gels thus offer an appealing alternative to these current methods by allowing sequential casting of building blocks with desired shapes and subsequent assembly of those building blocks via self-adhesion. In the context of biomedical applications, hyaluronic acid (HA) is frequently used as a backbone polymer for self-healing and self-adhesive polymer structures given its excellent gelforming properties and biological activity.25-27 While multiple chemistries have been explored to prepare self-healing HA, phenylboronic acid (PBA) interactions with cis-diol containing carbohydrates or polymers with multiple pendant -OH groups offer significant advantages in terms of facilitating rapid, highly reversible, and cytocompatible covalent crosslink formation.28 For example, 3-aminophenylboronic acid-conjugated HA can undergo gelation and subsequent self-healing with maltose-functionalized HA at physiological pH.29 However, the mechanical strength of such hydrogels was low (G’
