While biomaterials were traditionally designed to be inert in a biological environment, new biomaterials capable of triggering specific biological responses at the tissue/material interface have been reaching clinical application. We are developing new biomaterials with enhanced physical properties and specific biological activity. This aspect of our work involves the design and synthesis of new polymers (synthetic and naturally-derived), the development of new processing approaches for existing polymers, and extensive physical and biological characterization of the resulting tissue engineering scaffolds.
Active and next-generation biomaterials:
We are designing biomaterials that are multifunctional, dynamic, and capable of being triggered externally on demand (Fig. 1). These biomaterials provide several different types of information to cells in their environment, and thus mimic many functions of the native extracellular matrices found in tissues. Tools from the biology community are enabling high-resolution and high-throughput bioassays that can help achieve unprecedented functionality, but their use can result in data explosions. To effectively match the information content of an assay with the goal of the experiment, material screens and bioassays must be arranged in specific ways. We are developing frameworks for the incorporation of next-generation bioassays into biomaterials design.
A variety of chemistries are being explored to create new types of materials, and new functionalities. Click chemistries provide orthogonal reactivity to the chemistries of the body, and are being exploited to create a variety of new crosslinking approaches for polymers, and targeting approaches in drug delivery. These chemistries are combined with chemical modification to provide materials capable of delivery into the body via a variety of strategies, and with tightly controlled degradation properties.
Figure 1. Active tissue adhesive for tissue mechanotherapy. Credit: Sungmin Nam.
Biomaterial Interfaces:
We are developing materials, specifically hydrogels, with enhanced physical properties to enable new applications in medicine. While hydrogels are generally very weak, we are developing strategies to toughen these materials. Adhesion to wet and dynamic tissue surfaces is important in many fields of medicine, but has proven extremely challenging. Existing adhesives are either cytotoxic, adhere weakly to tissues, or cannot be utilized in wet environments. We are developing biologically-inspired designs for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energy on wet surfaces than existing adhesives, and are currently being explored for their utility as tissue adhesives, wound dressings, hemostatic agents, and tissue repair (Fig. 2).
Figure 2. Tough adhesive being stretched from pig heart. Credit: Jianyu Li.
The new biomaterials developed in the laboratory may be used in a variety of drug delivery, immunotherapy, and regenerative medicine projects to promote the regeneration or targeted destruction of tissues in the body (see Drug Delivery, Immunotherapy and Immunoengineering, Tissue Engineering and Regenerative Medicine sections). The future of new biomaterials is dependent upon the development of an enhanced knowledge base of molecular, cellular, and tissue interactions with materials. A major focus of our work is broadening our mechanistic understanding of tissue/material interactions, enabling development of design criteria from a biological perspective.
Relevant review articles in this area
- Darnell M, Mooney DJ. Leveraging advances in biology to design biomaterials. Nat Mater. 2017;16(12):1178-1185. doi:10.1038/nmat4991.
- Huebsch N, Mooney DJ. Inspiration and application in the evolution of biomaterials. Nature. 2009;462(7272):426-432. doi:10.1038/nature08601.
Representative research publications in this area
- Li J, Celiz AD, Yang J, et al. Tough adhesives for diverse wet surfaces. Science. 2017;357(6349):378-381. doi:10.1126/science.aah6362.
- Nam, S., Seo, B.R., Najibi, A.J. et al. Active tissue adhesive activates mechanosensors and prevents muscle atrophy. Nat. Mater. 22, 249–259 (2023). https://doi.org/10.1038/s41563-022-01396-x.
- Zhao X, Kim J, Cezar CA, et al. Active scaffolds for on-demand drug and cell delivery. Proc Natl Acad Sci. 2011;108(1):67-72. doi:10.1073/pnas.1007862108.
- Rowley JA, Madlambayan G, Mooney DJ. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials. 1999;20(1):45-53.
- Harris LD, Kim BS, Mooney DJ. Open pore biodegradable matrices formed with gas foaming. J Biomed Mater Res. 1998;42(3):396-402.