Cross-linking of a Biopolymer-Peptide Co-Assembling System

Publication date: Available online 18 May 2017
Source:Acta Biomaterialia
Author(s): Karla E. Inostroza-Brito, Estelle C. Collin, Anna Poliniewicz, Sherif Elsharkawy, Alistair Rice, Armando E. del Río Hernández, Xin Xiao, José Rodríguez-Cabello, Alvaro Mata
The ability to guide molecular self-assembly at the nanoscale into complex macroscopic structures could enable the development of functional synthetic materials that exhibit properties of natural tissues such as hierarchy, adaptability, and self-healing. However, the stability and structural integrity of these kinds of materials remains a challenge for many practical applications. We have recently developed a dynamic biopolymer-peptide co-assembly system with the capacity to grow and undergo morphogenesis into complex shapes. Here we explored the potential of different synthetic (succinimidyl carboxymethyl ester [SCM-PEG-SCM], poly (ethylene glycol) ether tetrasuccinimidyl glutarate [4S-StarPEG] and glutaraldehyde) and natural (genipin) cross-linking agents to stabilize membranes made from these biopolymer-peptide co-assemblies. We investigated the cross-linking efficiency, resistance to enzymatic degradation, and mechanical properties of the different cross-linked membranes. We also compared their biocompatibility by assessing the metabolic activity and morphology of adipose-derived stem cells (ADSC) cultured on the different membranes. While all cross-linkers successfully stabilized the system under physiological conditions, membranes cross-linked with genipin exhibited better resistance in physiological environments, improved stability under enzymatic degradation, and a higher degree of in vitro cytocompatibility compared to the other cross-linking agents. The results demonstrated that genipin is an attractive candidate to provide functional structural stability to complex self-assembling structures for potential tissue engineering or in vitro model applications.Statement of significanceMolecular self-assembly is widely used for the fabrication of complex functional biomaterials to replace and/or repair any tissue or organ in the body. However, maintaining the stability and corresponding functionality of these kinds of materials in physiological conditions remains a challenge. Chemical cross-linking strategies (natural or synthetic) have been used in an effort to improve their structural integrity. Here we investigate key performance parameters of different cross-linking strategies for stabilising self-assembled materials with potential biomedical applications using a novel protein-peptide co-assembling membrane as proof-of-concept. From the different cross-linkers tested, the natural cross-linker genipin exhibited the best performance. This cross-linker successfully enhanced the mechanical properties of the system enabling the maintenance of the structure in physiological conditions without compromising its bioactivity and biocompatibility. Altogether, we provide a systematic characterization of cross-linking alternatives for self-assembling materials focused on biocompatibility and stability and demonstrate that genipin is a promising alternative for the cross-linking of such materials with a wide variety of potential applications such as in tissue engineering and drug delivery.

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