Totally tubular: Polymer plumbing for tissue engineering

Photos of polymer hydrogel tube tied in a knot and stretched by a researcher wearing purple gloves.

Original paper: Multilayer Tubes that Constrict, Dilate, and Curl in Response to Stimuli

Content review: Danny Seara
Style review: Arthur Michaut


Our bodies rely on many types of tube-shaped organs to transport blood, air, water, food, urine, and feces. These tubular organs are stimuli-responsive: they can constrict or dilate, secrete chemicals, or act as a selective barrier in response to biological signals. Developing synthetic versions of natural tissue structures that mimic biological responses is at the cutting edge of tissue engineering, synthetic organ development, and even soft robotics design. But what materials can be used to grow responsive tubes in the lab? Many of the fundamental building blocks of biological tissues are naturally occurring polymers. However, growing stimuli-responsive tissue mimics with these materials has not been achieved. Fortunately, many examples of biological tissue have similar properties to synthetic polymer hydrogels which are easy to make in the lab. Polymer hydrogels are made of interconnected networks of synthetic polymer chains, linked together by crosslinker molecules and swollen with water – kind of like a wet sponge as shown in Figure 1. However, many processes that are currently used to make tubes from hydrogels require specialized equipment, like coaxial printing which requires many different custom-made print heads to make different sized tubes. In addition, such techniques don’t easily produce branched tubes common in biological systems. Recently, a group of engineers designed a simple and elegant method to construct stimuli-responsive millimeter-scale biomimetic tubes using a simple patterning process.

Colorful cartoon schematic showing the stepwise process of polymerization from iniator, monomer, and crosslinker small molecule to crosslinked polymer chains to hydrogel materials.
Figure 1. Synthetic crosslinked polymer are made by combining initiator, monomer, and crosslinker molecules (a) and initiating a polymerization reaction (b). This results in the formation of polymer chains that are crosslinked by covalent bonds (c) to form very large network molecules (d). When these networks swell in water, they form hydrogels (e). Hydrogels can be engineered to have similar water-to-organic content and mechanical properties as biological tissue.

To make tube-like structures, the researchers first mold a cylindrical template using the biopolymer agar (a natural vegetable gelatin) and then infuse it with initiator molecules. To grow a polymer hydrogel around the template, the agar cylinder is suspended in a bath containing monomer and crosslinker molecules. Once activated, the initiator molecules can leak out and interact with the monomers and crosslinkers in the bath to polymerize a hydrogel sleeve around the template. The researchers also added xanthan gum to thicken the monomer bath so the template can be suspended and a structurally sound tube can be grown (no cracks, holes, or missing tube walls). Finally, the agar template is dissolved in hot water, leaving a synthetic hydrogel tube. Figure 2 shows a schematic of this “inside-out” polymerization process.

Colorful cartoon schematic showing the stepwise process to make polymer hydrogel tubes with two photographs showing the finished tubes.
Figure 2. The simple method to grow synthetic polymer hydrogel tubes around degradable agar templates is represented by this schematic. Scale bars represent 4 mm. Schematic design and images courtesy of the original article.

The researchers were able to fabricate tubes with different geometries and patterns, growing proof-of-concept mimics of naturally occurring biological tube structures. Changing the diameter of the template cylinder controlled the size of the lumen (inner diameter) of the tube. The researchers could vary the lumen by an order of magnitude, from 4.5 millimeters down to 0.6 millimeters. A 20-minute “inside-out” polymerization reaction produced tubes with ~1 millimeter thick tube walls. Increasing the concentration of initiator in the template or the polymerization reaction time produced thicker tube walls. Adding xanthan gum to the monomer bath modified its viscosity and allowed the researchers to spatially separate different monomer species in the bath from left to right or top to bottom. In this way they could create patterned hydrogel tubes, such as tubes with lateral patterns (rings around the tube) and longitudinal patterns (stripes along the tube walls), as shown in Figure 3. By designing different hydrogel tube patterns, the researchers were able to grow synthetic tubes that responded to different stimuli much like biological tubes respond to stimuli in living organisms. 

Colorful cartoon schematic showing the stepwise process to make polymer stimuli-responsive hydrogel tubes using a different stripe patterns.
Figure 3. Shape-changing synthetic hydrogel tubes are made using viscous patterned monomer baths to embed lateral patterns (a) or longitudinal patterns (b). Three types of hydrogels were used to make these patterns: (i) a hydrogel that is non-responsive to temperature- or pH-based stimuli; (ii) a hydrogel that responds to increased temperature by contracting (shrinking in volume); and (iii) a hydrogel that responds to pH change by expanding (growing in volume). Schematic design and images courtesy of the original article.

The researchers used monomers that form responsive polymers to pattern the tubes and achieve different tube responses. The laterally-patterned tubes constricted with temperature changes and dilated in response to chemical triggers, like pH change. The longitudinally-patterned tubes curled into loops with temperature change. These coils formed because the tube components responded differently to changes in temperature (one component expanded more than the other) which caused the tube to bend. The researchers were even able to make rudimentary branched systems where the branches from the main tube could be programmed for different stimuli-response properties. 

A really exciting aspect of this method is that it works at physiological conditions (room temperature, aqueous environments, etc.). This means cells or other bioactive materials can be incorporated during tube-making, which is advantageous for regenerative medicine. This work is a great example of translating the fundamental study of polymers and responsive materials into real world applications. It also suggests many new engineering questions: Can we make synthetic and responsive tube systems from biopolymer hydrogels (like collagen or cellulose)? Can we incorporate synthetic tubes into other soft materials like gels or colloids to make complex structures? Can synthetic tubes be designed as chemical reaction conduits or implantable biological sensors? Can soft robots use tube systems for autonomous motion? The industrious tube engineer might imagine designing a patterned multi-tube system to generate tube-shaped robots that can crawl or grab objects using coiling tube tentacles. Ultimately, this work helps set the trajectory of future research as we head towards our not-so-distant future full of engineered tubular organs and squishy robots.

For the People, By the People: Early career researchers organize virtual polymer physics symposium

2020 Virtual Polymer Physics Symposium

Symposium Website: 2020 Virtual Polymer Physics Symposium


In these unprecedented and fluid times, conferences and symposia have gone virtual as STEM collectively settles into a new normal. Many large meetings, like the formerly “in-person only” American Physical Society (APS) and American Chemical Society (ACS) national meetings, have been canceled or transitioned to virtual-only participation this year. The 2021 Spring APS meeting will go virtual as well. I love big in-person meetings and have shied away from virtual alternatives thinking they would not provide the same feeling of community with my fellow scientists. However, the isolation of quarantine and the desire to get comfortable with the “new normal” motivated me to step out of my comfort zone and into the world of virtual science meetings this summer. So, when the opportunity to attend the 2020 Virtual Polymer Physics Symposium (VPPS) arose in July, I jumped at the chance to participate. 

The 2020 VPPS was a two-day virtual event organized to fill the void left by the cancellation of the 2020 Polymer Physics Gordon Research Seminar . The event was organized by two early career researchers (ECRs), Konane Bay from Princeton, and Whitney Loo from UC Berkeley, the current co-chairs of the Polymer Physics Gordon Research Seminar (GRS). 

The Polymer Physics GRS is held biennially; the last seminar was in 2018 and, due to the pandemic, the next one won’t occur until 2022. “Two years feels like a lifetime to ECRs and we know many of our colleagues will be at different institutions and career stages in 2022, so we wanted to create a space for them to share and discuss their recent research,” explains Konane. The 2020 VPPS connected more than 100 scientists, including 20 ECRs presenting their work across four oral presentation sessions during the two-day event. In the spirit of the Polymer Physics GRS, this new virtual event also incorporated professional development and discussion sessions, including a Mentorship Panel and the “Dispersity and Diversity Hour” discussion focused on how to increase diversity, equity, and inclusion (DEI) in the field of polymer physics and the broader scientific community.

The Mentorship Panel included researchers at different career stages working in academia, industry, or government research. The discussion was focused on steps students and postdocs can take to prepare for future careers in polymer physics as we adapt to a global pandemic. The panelists emphasized the quarantine-proof nature of computational work since it can often be done anywhere including at home and encouraged experimentalists to broaden their computational skill set. Both Nate Lynd, assistant professor at UT Austin, and Michelle Sing, an engineer at Braksem USA, suggested that experimentalists should become familiar with Python as a first step. Debra Audus, a scientist at NIST, highlighted lab work automation and strategic experiment planning to maximize “in-lab” time during the transition to shift-style lab work that many American universities have adopted as a way to overcome the challenges related to performing socially distanced science. 

Participating in the “Dispersity and Diversity Hour” required some homework. The organizers asked all attendees to prepare for the discussion by reading about the experience of Black researchers in STEM (links below). Ben Yavitt, a Stony Brook University postdoc, opened the event by emphasizing that the goal of the discussion was to brainstorm potential solutions to address the issues spotlighted by national movements such as #BLM, #ShutdownSTEM, and #BlackintheIvory. More than 70 attendees participated in small group discussions across 15 breakout rooms led by volunteer discussion leaders. This event was an important first step in raising awareness of the necessary academic culture shift required to empower more scientists of color to pursue careers in soft matter and polymer physics.

Overall, the meeting events were very well moderated and designed for maximum virtual engagement during both the science presentations and the discussion sessions. For me, attending this event clarified the current trajectory of the polymer physics field as it transitions from fundamental studies to applied research focused on exploiting polymer physics for advanced technology. This transition in research focus was evident in some of the science presented during the symposium. While I was apprehensive about the shift to virtual meetings and conferences, attending the 2020 VPPS has won me over. I highly recommend taking advantage of the proliferation of virtual science conferences and symposia to stay engaged, learn about new science and perspectives, and do some networking along the way!

Diversity and Diversity Hour Resources
Science Is For Everyone — Until It’s Not
Your Black Colleagues May Look Like They’re Okay — Chances Are They’re Not
AIP Team-Up Report Executive Summary

Disclosure: I am acquainted with Konane Bay, one of the event co-organizers. She was a graduate student in my department, UMass Amherst Department of Polymer Science and Engineering. However, I was not involved in any way with the organization of the VPPS.