Toward Adipose Tissue Engineering Using Thiol-Norbornene Photo-Crosslinkable Gelatin Hydrogels

Nowadays, breast implants, lipofilling, and microsurgical free tissue transfer are the most often applied procedures to repair soft tissue defects resulting from mastectomies/lumpectomies following breast cancer. Due to the drawbacks and limitations associated with these conventional clinical practices, there is a need for alternative reconstructive strategies. The development of biomimetic materials able to promote cell proliferation and adipogenic differentiation has gained increasing attention in the context of adipose reconstructive purposes. Herein, thiol-norbornene crosslinkable gelatin-based materials were developed and benchmarked to the current commonly applied methacryloyl-modified gelatin (GelMA) with different degrees of substitutions focussing on bottom-up tissue engineering. The developed hydrogels resulted in similar gel fractions, swelling, and in vitro biodegradation properties compared to the benchmark materials. Furthermore, the thiol-ene hydrogels exhibited mechanical properties closer to those of native fatty tissue compared to GelMA. The mechanical cues of the equimolar GelNB DS55% + GelSH DS75% composition resulted not only in similar biocompatibility but also, more importantly, in superior differentiation of the encapsulated cells into the adipogenic lineage, as compared to GelMA. It can be concluded that the photo-crosslinkable thiol-ene systems offer a promising strategy toward adipose tissue engineering through cell encapsulation compared to the benchmark GelMA.

Automated summary

In this study, thiol-norbornene crosslinkable gelatin-based materials were developed and compared to commonly used methacryloyl-modified gelatin (GelMA) in the context of adipose tissue engineering. The newly developed thiol-ene hydrogels showed similar gel fractions, swelling, and in vitro biodegradation properties, with mechanical properties closer to native fatty tissue compared to GelMA. The equimolar GelNB DS55% + GelSH DS75% composition not only exhibited similar biocompatibility but also superior differentiation of encapsulated cells into the adipogenic lineage, promising a new strategy for adipose tissue engineering.