Akademik Veri Yönetim Sistemi
The International Conference on Biofabrication 2025, Warszawa, Polonya, 14 - 17 Eylül 2025, sa.185, ss.61, (Özet Bildiri)
Fibrin-based biomaterials are highly valued for their biocompatibility,
hemostatic function, and clinical use in wound healing [1]. However, their
widespread 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 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, ex vivo subcutaneous implantation, and a
drill-hole bone defect model. Furthermore, 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 CBP pattern. Subcutaneous implants showed deep
tissue infiltration without adverse inflammatory response. In the drill-hole
model, patterned membranes supported localized bone deposition. 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 bioconvergent 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 competent, 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.