Project Portugal 2030

Summary

The novelty of TRHIvE relies on the design of new functional building blocks using multifunctional recombinant proteins with osteogenic and anti-tumoral activity to hinder BM and support the regeneration of healthy bone tissue. To achieve this goal, TRHIvE aims to develop advanced therapeutics capable of effectively inhibiting metastatic tumour growth, enhancing bone tissue regeneration, and preserving skeletal integrity to improve patient outcomes and quality of life. This goal will be met by pursuing three specific objectives: (i) To use recombinant DNA technology to explore and produce multifunctional chimeric proteins with biological functional domains, such as osteogenic or anti-tumoral peptides.; (ii) To use advanced 3D printing technologies to assemble tissue-specific hydrogel with protein gradients for tuning their bioactivity; (iii) To validate the biological compliance and anti-tumour capacity of the developed constructs to promote bone tissue regeneration while impairing BM. Engineered biomaterials seek to modulate the unique properties of human tissues by providing a microenvironment that potentiates the adhesion and proliferation of living cells. The goal is to replicate native tissue and provide biological cues for self-regeneration, self-healing, environmental responsiveness, and homeostasis. Most currently available medical solutions fail to secure proper bone tissue healing and do not hinder the formation of BM in diseased tissue. The use of spider silk proteins will outperform orthopaedic solutions due to their biocompatibility, strength, immunogenicity, and biodegradability. Recombinant DNA technology allows the design and production of novel protein biomaterials with significant functional bioactive cues, eliminating the need to add chemical modification or supplementation. Furthermore, recombinant production is considerably faster than conventional extraction methods from animals. Spider silk proteins will be endowed with functional (osteogenic and anti-tumour cues) properties crucial to developing functional protein polymers that can be processed into biomaterials of remarkable properties. Besides the exceptional biophysical properties, the slow biodegradability provided by spider silk enables it to maintain the necessary mechanical and biological properties until new tissue can be formed. Protein hybrids will be employed to build adjustable, bio-instructive, multifunctional hierarchical scaffolds employing advanced manufacturing technologies. This method allows automated, continuous, and flexible hydrogel assembly with adjustable shape, size, and composition. Using a layered hydrogel, TRHIvE can replicate the bone tissue environment, a feature that current medical solutions lack. Recombinant proteins' biochemical/biomechanical signals will direct cell response and avoid anti-tumour medication supplementation in the novel material's local microenvironments for in-cell growth. It will also enable designed hybrid materials to integrate with the host tissue environment for long-term stability, functioning, and biocompatibility for therapeutic effects and tissue regeneration. The proposed method will revolutionise regenerative medicine by combining functionalized proteins and structural properties at the tissue level with a bioinstructive microenvironment at the cellular level. It can be applied to other fibrous tissues (skeletal and cardiac muscles) or to other applications (wound healing, patches).