Speaker
Description
Fibrin-based biomaterials are clinically established for their biocompatibility, resorbability, and hemostatic function, and have found widespread use in surgical sealants and wound repair [1]. However, their application in bone regeneration remains limited due to intrinsic softness, fast degradation, and poor mechanical tunability [2]. To address these shortcomings, we present a novel, multiscale fabrication strategy that integrates sound-guided hydrodynamic assembly with supramolecular peptide self-assembly, enabling the creation of mechanically tunable and osteoconductive peptide–fibrin hybrid membranes.
Hybrid membranes were fabricated using a one-pot process in which bioactive peptide amphiphiles (PAs) co-assembled with fibrinogen during a thrombin-mediated cross-linking. PAs were decorated with bone morphogenetic protein-2 (BMP-2) binding epitopes to promote osteoinductive signaling [3]. Simultaneously, calcined bone particles (CBPs) were patterned within the precursor via Faraday wave-induced acoustic fields (25-143 Hz). The process enabled spatial organization of CBPs during cross-linking while promoting peptide nanofiber integration. A computational model was used to correlate pattern formation with the acoustic parameters. The functional membranes were thoroughly characterized by mechanical properties, cellular infiltration, and particle distribution. Biological response was evaluated through in vitro human mesenchymal stromal cells (hMSC) culture and an immunological profiling was conducted using peripheral blood mononuclear cells (PBMCs) and Olink proteomic analysis.
The fabrication process resulted in radially patterned distributions of CBPs embedded in a peptide–fibrin nanofibrous mesh. The supramolecular assembly of PAs increased the overall stiffness of the membrane, while sound-guided hydrodynamic patterning generated anisotropic mechanical properties tunable via acoustic frequency. A theoretical-experimental relationship was established between wave frequency and resulting membrane stiffness. In vitro, the membranes supported high hMSC viability, promoted cell infiltration, and maintained the integrity of the CBPs pattern. Proteomic analysis of PBMC-conditioned media revealed upregulation of osteogenic and remodeling-associated cytokines, suggesting that the materials can activate pathways associated with osteogenic commitment and bone remodeling.
This study introduces a novel fabrication strategy that converges peptide self-assembly with sound-guided hydrodynamic assembly to yield a mechanically reinforced, biologically active hybrid material. Unlike conventional cross-linking or filler-based reinforcement, this approach provides precise multiscale control over structure and function. The ability to pattern mineral particles and co-assemble peptide nanostructures within fibrin provides new opportunities for designing customizable biomaterials for bone-related applications. While regenerative outcomes remain at a proof-of-concept stage, the method establishes a robust, scalable platform for the biofabrication of mechanically-enhanced, osteoconductive membranes.
[1] Jackson MR. Fibrin sealants in surgical practice: An overview. Am J Surg. 2001 Aug;182(2 Suppl):1S-7S. doi: 10.1016/s0002-9610(01)00770-x. PMID: 11566470
[2] Litvinov RI, Weisel JW. Fibrin mechanical properties and their structural origins. Matrix Biol. 2017 Jul;60-61:110-123. doi: 10.1016/j.matbio.2016.08.003. Epub 2016 Aug 20. PMID: 27553509; PMCID: PMC5318294.
[3] Halloran D, Durbano HW, Nohe A. Bone Morphogenetic Protein-2 in Development and Bone Homeostasis. J Dev Biol. 2020 Sep 13;8(3):19. doi: 10.3390/jdb8030019. PMID: 32933207; PMCID: PMC7557435.
64057827009