Special Poster Session Biofabrication
Introduction: Targeted therapies with biologicals are of growing clinical importance in the treatment of autoimmune diseases or cancer. Although auspicious, there are limitations in the broad medical application: the production of biologicals is complex and expensive and the serum half-life time of some biologicals is short requiring frequent injections or infusions. The generation of a drug-producing tissue container vascularized by an AV loop and implanted in the patient seems to be a promising approach to solve this problem. This study aimed at the establishment of an ideal carrier matrix based on recombinant engineered spider silk for the generation of a transplantable therapeutic tissue container.
Materials and methods: For cytocompatibility and drug release testing in vitro, genetically modified HEK293 cells, producing a reporter molecule consisting of the extracellular domain of TNFR2 linked to luciferase, were incorporated into recombinant engineered ADF4(C16)-RGD spider silk. Furthermore, biocompatibility and angiogenesis were assessed in the rat AV loop model using µCT and histology.
Results: Modifying the eADF4(C16) spider silk with the RGD motive supported cell viability as well as the production of the reporter molecule. Moreover, we were able to prove a slow biodegradation and incipient vascularization of constructs containing eADF4(C16)-RGD spider silk. Although, macrophages were present in the histological specimen no signs of severe immunoreaction were observed.
Conclusion: This study demonstrates the impact of modifying engineered ADF4(C16) spider silk with functional groups on cytocompatibility, protein production as well as angiogenesis. The use of engineered ADF4(C16)-RGD spider silk enables new possibilities for the establishment of a transplantable therapeutic tissue container.