Yang Zhilu, research fellow from the School of Materials Science and Engineering at Southwest Jiaotong University, recently published a paper entitled “A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic” in Research, the first one in the Science Partner Journal (SPJ) program since the top journal’s foundation in 1880.

Ideal biomedical implants should have the abilities to actively integrate the surrounding tissues and cells, provoke cell responses, maintain tissue and organ functions, and even combat hostile microorganisms. Surface biofunctionalization exemplifies one of the most straightforward ways to endow biomaterials with function and vitality. As a typical method, physical adsorption or chemical conjugation of biological functional molecules can, to a certain extent, enable inherently bioinert materials to modulate cell-material interactions, induce specific cell behaviors, and subsequently generate relevant biological effects. However, long term biological activities cannot be maintained for reason of serious molecular leakage with such a method. In comparison, the one of chemical conjugations shows stronger molecular anchoring, but its application is often impeded by the tedious reactions as well as sophisticated surface treatment technologies. Inspired by the marine mussel organisms, Lee and his colleagues developed a novel surface engineering method in 2007. The molecular mechanism of this method derived from mussel foot proteins (e.g., Mytilus edulis foot proteins, Mfps), in which the repetitive catechol residues of DOPA (3, 4-dihydroxy-L-phenylalanine) can produce covalent and non-covalent comediated molecular adhesion. Lee also used dopamine molecules containing catechol to achieve stable adhesion to virtually all kinds of substrates under wet conditions. Moreover, amino- or thiol-mediated Michael addition and Stiff base allows a variety of biofunctionalizations. Though the dopamine method can provide a common strategy for surface biofunctionalization, the second-step reaction through Michael reaction and Schiff base inhibits biomolecule activities with the inevitable consumption of essential amino and thiol groups. Additionally, the low specificity and efficiency of this kind of reactions weaken the reproducibility and controllability (e.g., heterogeneous molecular conjugation and random molecular orientation). Therefore, potential as it is, the mussel-inspired molecular adhesion demands for improvement.

Scheme 1. The molecular binding mechanisms of mussel-inspired peptide adhesion and bioorthogonal molecular conjugation for surface bioengineering.

Recently, Yang Zhilu, a research fellow at our University, and Prof. Pan Guoqing of Jiangsu University cooperated to report an advanced surface bioengineering strategy by combining mussel-inspired molecular adhesion and bioorthogonal click reaction. Bioorthogonal click reaction (e.g., the dibenzylcyclooctyne-azide (DBCO-azide) cycloaddition chemistry) has advantages like specificity, rapidity, thoroughness, and biocompatibility. Thus, they designed and synthesized a peptide mimic with catechol groups and azide groups (e.g. (DOPA)4-Azide) (Scheme 1). Based on mussel-inspired molecular adhesion, (DOPA)4-Azide can be stably bound to the surface of metal, inorganic and organic polymer materials to obtain an azide surface. The authors synthesized several typical DBCO-modified biomolecules with abilities to modulate cell-material interactions and induce specific biological effects. With azide (DOPA)4-Azide, several typical biofunctionalization, such as antibiofouling, antibacterial, and antithrombotic activity, were achieved (Figure 1). The research demonstrates that the surface bioengineering strategy based on bioclickable and mussel adhesive peptide mimic have broad applicability in both the substrate materials and their intended functions. Since DBCO modification is industrially mature, the authors anticipated that a “clean” molecular modification based on bioorthogonal click chemistry and a mussel-inspired surface adhesion mechanism may synergistically provide a widely used general strategy for surface biofunctionalization.

The related research results, recorded in the paper “A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic”, were published in the internationally renowned journal Research, the first one in the Science Partner Journal (SPJ) program since the top journal’s foundation in 1880. Yang Zhilu and Pan Guoqing are the corresponding authors of the paper, Graduate Xiao Yu is the first author, and the School of Materials Science and Engineering of Southwest Jiaotong University is the authors’ first affiliation. The research was supported by the National Key Research and Development Program and the National Natural Science Foundation of China, etc.

(Paper link: https://spj.sciencemag.org/research/2020/7236946/)

Figure 1. a) Structural formula of the bio-clickable mussel-inspired peptide mimic DOPA4-Azide and PEGylated antifouling TiO2 surface. b) a) Structural formula of the DBCO-modified antibacterial peptide and fabrication of an antibacterial PVC surface. c) Structural formula of the DBCO-modified cyclen DBCO-DOTA with the ability to chelate Cu (II) and the fabrication of antithrombogenic surface on 316L SS substrate.

About Yang Zhilu

Yang Zhilu, research fellow and doctoral supervisor, was the winner of “Outstanding Youth Fund of Sichuan Province”, the reserve candidate of “Academic and Technical Pioneers of Sichuan Province”, and the “Yang Hua Scholar” of Southwest Jiaotong University. He presently acts as chief editor of Smart Materials in Medicine, editor of Engineered Regeneration, and guest editor of Bioactive Materials and Medical Gas Research, all of which are KeAi international journals. He currently focuses on the studies of the pathologic mechanism of atherosclerosis plaque in coronary arteries, nano-targeted drugs for the treatment of coronary/peripheral artery disease, drug balloons and vascular stents with functions of lesion cure and vascular tissue repair. Up to date, he has published over 40 SCI papers as the first/corresponding author in top journals, such as PNAS, Research (2 papers), Chemistry of Materials, Biomaterials (9 papers), including 10 papers with IF greater than 10 and 7 papers with IF between 8-10. He has delivered lectures and been invited to deliver lectures at over 10 international/national conferences. He has obtained 14 invention patents including 1 in the United States. His independent intellectual property right “biodegradable stent coating with functions of lesion cure and vascular tissue repair” has been successfully transferred (transfer fee: RMB 15 million).