Chemically and structurally directed shape morphosis in hybrid aerogels for bone tissue engineering - Toward designing smart biomimetic 3D scaffold for bone cancer therapy and bone repair

• Applicant: Dr. Hajar Maleki
• Subject Area: Biomaterials ; Synthesis and Properties of Functional Materials
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 467116484

The treatment of malignant bone tumors and the regeneration of the bone defects resulted from tumor resection is still a significant clinical challenge. The treatment of such a tumor-initiated large bone defect typically requires implanting the biomimetic 3D porous materials with the dual functionality of killing the residual bone tumor cells through local chemo-/photothermal therapy followed by subsequent regeneration of the bone defects. In addition, vascularization or blood vessel formation beside osteogenesis in the defect site is another major challenge in the process of bone formation, which requires a specific structural consideration in the scaffold. Both therapeutic and new bone regeneration competence (osteogenesis and angiogenesis) of the 3D scaffold are governed by control on its micro-structural, cell responsivity, and therapeutic functionalities. To address these challenges, the fabrication of appropriate cell scaffolding materials meeting all requirements for optimal biological and tumor therapeutic functions are vitally important. Aerogels from physical and microstructural aspects, namely for their high pore volume, pore interconnectivity, and extensive internal surface area, are promising biomaterials in bone tissue engineering. In this work, the principle goal is to develop a series of bifunctional surface-modified silk fibroin (SF) composite aerogel scaffolds combining a high photothermal effect and new bone tissue and vasculature formation through a synergistic combination of surface-modification, self-assembly, and 3D-printing strategies. The particular self-assembling capabilities of cell adhesive peptide modified SF in solution together with hybridization of the resulted SF polymer with 1D (electrospun hollow silica nanofiber) and 2D nanosheets (antimonene) as inorganic nanofillers, and 3D printing of the resulted composite gel could afford 3D materials with an interconnected channel like porosity, cancer cells photothermal ablation and bone regeneration potential. As a major part of the envisaged work, state-of-the-art techniques such as interpenetrating networks or surface grafting and a combination of novel 3D printing and temporary templating of SF-based hybrid scaffolds will be explored to advance current scaffold microfabrication techniques. The most promising 3D scaffold will be studied from bone regeneration and therapeutic aspects. This includes in-vitro tests, mainly osteogenic differentiation, angiogenesis, stimuli-responsive drug-releasing, and bone cancer cell ablation. It is expected that the combination of 3D printing and self-assembling of SF and incorporation of inorganic nanofillers to the final scaffold endow the materials with distinct bifunctional properties of therapy and bone regeneration.

• DFG Programme: Research Grants
• International Connection: Austria, Portugal
• Co-Investigators: Professor Dr.-Ing. Aldo Boccaccini; Professor Dr. Sanjay Mathur; Professorin Dr.-Ing. Irina Smirnova
• Cooperation Partners: Professorin Dr. Nicola Hüsing; Professor Dr. João F. Mano