Biotechnology and Bioprocess Engineering 2024; 29(2): 291-302  
Catechol‑ and thiol‑containing binder that aggregates granular xenografts in reconstructed bone defects by mimicking mussel wet adhesion
Seung Jun Lee1 · Ki Baek Yeo2 · Dohoon Lee3 · Dong Soo Hwang3,4,5 · Sang Ho Jun1
1 Department of Oral and Maxillofacial Surgery, Korea University Anam Hospital, Seoul 02841, Korea
2 Institute for Clinical Dental Science, Korea University Medical Center, Seoul 02841, Korea
3 Division of Environmental Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea
4 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea
5 Institute for Convergence Research and Education in Advanced Technology, Yonsei University International Campus I-CREATE, Incheon 21983, Korea
Correspondence to: Dong Soo Hwang
dshwang@postech.ac.kr
Sang Ho Jun
junsang@korea.ac.kr

Seung Jun Lee, Ki Baek Yeo and Dohoon Lee contributed equally to this work.
Received: July 2, 2023; Revised: September 21, 2023; Accepted: September 24, 2023; Published online: February 22, 2024.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Xenograft bone granules are bone graft materials that are widely used to reconstruct bone tissue in clinical practice, and their clinical success requires aggregation with a biocompatible binder. While the catechol mussel bioadhesive has been used as a key universal biomedical glue moiety, the thiols in mussel adhesive proteins have recently been shown to play key roles in mussel wet adhesion. Here, pentaerythritol tris(3-mercaptopropionate)-di-catechol (PETMP-di-catechol), a catechol- and thiol-containing binder molecule that mimics mussel adhesive proteins, was used to aggregate xenograft bone granules and reconstruct bone tissue. The PETMP-di-catechol-aggregated xenograft bone granules were most resistive to compression stress when both the catechol and thiol moieties in PETMP-di-catechol were chemically oxidized with sodium periodate. The xenograft bone granules aggregated with the oxidized PETMP-di-catechol exhibited enhanced osteogenic cellular behavior in vitro and in vivo in a rat calvarial defect model, compared to the control group treated with catechol-conjugated chitosan, a catechol-containing polymer binder devoid of thiol moieties. Hence, the thiol-containing catechol-functionalized binder exhibits improved bone tissue reconstruction properties by mimicking mussel wet adhesion. In addition, our study suggests that PETMP-di-catechol is a potential biocompatible bone binder for use in clinical settings.
Keywords: Catechol · Thiol · Bone granule aggregation · Bone tissue reconstruction · Implant · Adhesive

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