Research

Current Project

The synthesis of biocompatible, acrylate-free 3D printing resins that is based on a ABA triblobk copolyester.

A Major Unmet Need

EU parliament voted to phase out animal testing in 2021. In ths US, FDA commits to explore alternative methods that will replace animal testing in drug development. Organ-on-a-chip is a promising alternative because it mimics human physiology well in a highly controlled in vivo environment. Current fabrication of organ-on-a-chip, however, has poor z resolution, and is impractical to be automated to meet the increasing demand. Further, it almost exclusiively uses polydimethylsiloxane (PDMS). Although PDMS is biocompatible, its hydrophobicity and chemical inertness make it incompatible with many small-molecule test compounds and extrmemely difficult to functionalize.

Thiol-ene Photopolymers to the Rescue

3D printing can revolutionize organ-on-a-chip fabrication by enabling automated production of 3D objects with highly complex features. Unfortunately,the current market is saturated with acrylate-based resins with poor biocompatibility. Acrylates attack DNA and proteins, therefore decimating in vitro cell populations in a few hours. Thiol-ene photopolymers are acrylate-free. We thereby synthesized photopolymers via ring-opening copolymerization (ROCOP) of propylene epoxide, norborene anhydride (CPMA), and a custom chain transfer agent (CTA). The triblock architechture allows us to tune the mechnical properties by adjusting the length of each block.

Opportunites for Commercialization

Currently, I am applying for Ignite Fellow for New Ventures at Cornell University. The goal of the program is to build strong high-value new businesses, grow entrepreneur scientists and engineers, advance technology commercialization, and enrich Cornell’s venture ecosystem. This program will give me the necessary funding and network to explore the commercial prospects of my invention. ROCOP's compatibility with many CTAs will afford mateirals with tunable mechanical and physical properties, thus allowing me to target different market segments and applications. I envision my invention to not only penetrate the organ-on-a-chip market, but provide versatile biocomaptible resins to the broader biomedical engineering community.

Papers and Patents

Cytocompatible, Transparent, and Clickable
Resin for 3D Printing.

Warrick Ma & Yadong Wang

Abstract

Stereolithography (SLA) has revolutionized the aerospace and automotive industry by rapidly prototyping irregularly shaped parts and tools on demand with high efficiency and resolution. In biomedical engineering, SLA has seen its nascent applications in areas such as tissue engineering and dentistry. All commercial SLA resins, however, have poor biocompatibility that prevents their broader acceptance in biomedical applications. For instance, the fabrication of bio-microfluidics, especially 3D organ-on-a-chip, still widely uses soft lithography and micro molding, although SLA would have been faster, cheaper, and have higher precision in the z-axis. This has prompted the advent of several thiol-ene resins with good biocompatibility and tunable mechanical properties. However, the lack of commercial interest in thiol-ene resins highlights the need for more research with a focus on scalability, affordability, and versatility. Herein, we report a metal-free ring-opening copolymerization (ROCOP) to produce an ABA block copolyester on a 30-gram scale, which is unprecedented in the field of metal-free ROCOP. The synthetic strategy uses affordable cyclic anhydrides and epoxides to chain extend polypropylene sebacate—a polyester synthesized via polycondensation. This bridges the long-standing dichotomy between ring-opening copolymerization and polycondensation and enables the scalable synthesis of a thiol-ene resin (BC1). The 3D-printed materials are cytocompatible as well as optically transparent and have a 25 μm resolution. Furthermore, we can vary the mechanical properties by controlling the block lengths in the triblock structure. We believe that BC1, and more importantly the synthesis platform, will accelerate the discovery of biocompatible resins urgently needed for organ-on-a-chip and other biomedical devices.

Submitted to Bioactive Materials 2022.

Synthesis and Characterization of Alkyne-Functionalized Photo-Cross-Linkable Polyesters.

Warrick Ma, Xiaochu Ding, Ying Chen & Yadong Wang

Abstract

An alkyne-functionalized elastomer derived from sebacic acid, 1,3-propanediol, and alkyne-functionalized serinol is synthesized via melt condensation. A low-power UV lamp triggers the cross-linking rapidly via thiol–yne click chemistry. The cross-linking behavior is studied by photorheology and NMR spectroscopy. The resultant elastomer possesses mechanical properties similar to those of human soft tissues and exhibits in vitro degradability and good cytocompatibility.

ACS Omega 2022, 7 (18), 15540

The works above are convered under "Crosslinkable Functionalized Oligoesters and Polyesters, Methods of Making Same, and Uses Thereof" Ma Y, Ding X, Wang Y. Appl.#:PCT/US2022/050907. Filed:11/23/2022.

Programming Tools

I have developed automated workflows to plot mechanical testing data in R. Check out my Github for more!