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This project addresses unmet needs within orthopedic care, focusing specifically on non-union fractures and anterior cruciate ligament (ACL) rupture, through the development of novel treatment strategies. This will be done by using a novel biomaterial - spider silk - reknown for its biocompatibility and impressive mechanical properties. Specifically, we will build on our ability to produce artificial spider silk fibers using only water-based solutions and ambient temperatures to engineer a novel type of ligament replacements that optionally can harbor growth factors. In another line of research, we have invented a method for making hydrogels from soluble spider silk proteins. Human mesenchymal stem cells can be encapsulated in these hydrogels that form spontaneously and within minutes when the temperature is increased to 37°C. This groundbreaking achievement offers a promising avenue for the creation of injectable, optionally bioactive, scaffolds. Our research extends beyond scaffold development to explore the rejuvenation of MSCs sourced from elderly individuals, who often exhibit diminished regenerative capacity. This multidisciplinary approach, which integrates advanced biomaterials, tissue engineering techniques, and targeted cellular therapies, holds promise for transforming the management of fractures, ACL injuries, and critical bone defects.

The overall objective of this proposal is to increase our knowledge of how nature designs and produces high-performance sustainable fibers, and to invent bioinspired processes with the aim of making truly biomimetic spider silk fibers. Our research is focused on spider silk, the toughest fiber known to man, and the gland in which it is produced. We know that there are several cell types in the gland that secrete specific combinations of proteins, and these are added sequentially to the spinning feedstock, without mixing. This means that the spider silk fiber likely contains several layers, but the number of layers and their protein composition remain largely unknown. By using state of the art sequencing technologies we will determine the anatomical localization of the different cell types, and proteomics of silk fibers that are gradually dissolved will be used to fortify our findings. Finally, we will produce recombinant silk proteins and design spinning devices that allow us to recapitulate architecture and composition of the native silk fiber, and produce truly biomimetic artificial silk fibers.