The key reaction pairs tetrazines with strained alkenes in a rapid, catalyst-free click process. Because these complementary groups react selectively in biological environments, crosslinking can proceed under mild, aqueous conditions rather than requiring conditions that disrupt native cellular chemistry. This selectivity supports formation of biomaterial networks in the presence of living cells.
Once formed, the network's properties can be tuned through the biomaterial components and their crosslinking behavior. The resulting structure may provide selected mechanical properties, degradation characteristics, and biochemical presentation. In bioengineering, these parameters matter because they influence how a material supports cells, presents signaling molecules, or releases therapeutic cargo.
Avoiding an added catalyst helps keep the reaction compatible with biological environments and native cellular chemistry. The tetrazine-strained alkene pairing can therefore be used under mild, aqueous conditions, where functionalized polymers or proteins are joined without introducing a catalyst-dependent crosslinking step. This feature is especially relevant when cells must remain present during material formation.
A basic workflow begins with functionalizing polymers or proteins with complementary reactive groups. The modified components are then brought together in a mild, aqueous environment, where the groups react and create a covalent network. Depending on the design, this process can be performed while cells are present, enabling fabrication of cell-containing biomaterials.
Injectable hydrogels are a major format because crosslinking can create the network after delivery at the intended site. The same strategy can immobilize signaling molecules, encapsulate cells, support controlled drug delivery, or contribute to tissue repair. These uses connect reaction selectivity with practical biomaterial functions in regenerative medicine and other biomedical applications.
The ability to crosslink in the presence of living cells enables minimally invasive biomaterial fabrication, a useful feature for regenerative medicine. Engineers can create cell-containing hydrogels and related materials while maintaining compatibility with cellular chemistry. This capability expands applications toward tissue repair, biochemical signaling, and controlled delivery while allowing the network's properties to be adjusted for biological needs.