Hayashi Koichiro, Tokumaru Tatsuya, Shibahara Keigo, Taleb Alashkar Ahmad Nazir, Zhang Cheng, Kishida Ryo, Nakashima Yasuharu, Ishikawa Kunio
Department of Biomaterials, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
ACS Nano. 2025 Jan 14;19(1):520-534. doi: 10.1021/acsnano.4c10430. Epub 2024 Dec 27.
Repairing cartilage tissue is a serious global challenge. Herein, we focus on wood skeletal structures that are highly porous for cell penetration yet have load-bearing strength, and aim to synthesize wood-derived hydrogels with the ability to regenerate cartilage tissues. The hydrogels were synthesized by wood delignification and the subsequent intercalation of citric acid (CA), which is involved in tricarboxylic acid cycles and essential for energy production, and -acetylglucosamine (NAG), which is a cartilage glycosaminoglycan, among cellulose microfibrils. CA and NAG intercalation increased the amorphous region of the cellulose microfibrils and endowed them with flexibility while maintaining the skeletal structure of the wood. Consequently, the CA-NAG-treated wood hydrogels became twistable and bendable, and the acquired stiffness, compressive strength, water content, and cushioning characteristics were similar to those of the cartilage. In rabbit femur cartilage defects, CA-NAG-treated wood hydrogels induced the differentiation of surrounding cells into chondrocytes. Consequently, the CA-NAG-treated wood hydrogels repaired cartilage defects, whereas the collagen scaffolds, delignified wood materials, and CA-treated wood hydrogels did not. The CA-NAG-treated wood hydrogels exhibit superior structural and mechanical characteristics over conventional cellulose-fiber-containing scaffolds. Furthermore, the CA-NAG-treated wood hydrogels can effectively repair cartilage on their own, whereas conventional natural and synthetic polymeric materials need to be combined with cells and growth factors to achieve a sufficient therapeutic effect. Therefore, the CA-NAG-treated wood hydrogels successfully address the limitations of current therapies that either fail to repair articular cartilage or sacrifice healthy cartilage. To our knowledge, this is the pioneer study on the utilization of thinned wood for tissue engineering, which will contribute to solving both global health and environmental problems and to creating a sustainable society.
修复软骨组织是一项严峻的全球性挑战。在此，我们关注具有高孔隙率以利于细胞穿透但同时具备承重强度的木材骨骼结构，旨在合成具有再生软骨组织能力的木材衍生水凝胶。这些水凝胶是通过木材脱木质素以及随后在纤维素微纤维之间插入柠檬酸（CA）和N - 乙酰葡萄糖胺（NAG）合成的，其中柠檬酸参与三羧酸循环且对能量产生至关重要，N - 乙酰葡萄糖胺是一种软骨糖胺聚糖。CA和NAG的插入增加了纤维素微纤维的无定形区域，并赋予它们柔韧性，同时保持木材的骨骼结构。因此，经CA - NAG处理的木材水凝胶变得可扭转和可弯曲，并且所获得的硬度、抗压强度、含水量和缓冲特性与软骨相似。在兔股骨软骨缺损中，经CA - NAG处理的木材水凝胶诱导周围细胞分化为软骨细胞。因此，经CA - NAG处理的木材水凝胶修复了软骨缺损，而胶原蛋白支架、脱木质素木材材料和经CA处理的木材水凝胶则没有。与传统的含纤维素纤维支架相比，经CA - NAG处理的木材水凝胶具有优异的结构和力学特性。此外，经CA - NAG处理的木材水凝胶自身就能有效修复软骨，而传统的天然和合成聚合物材料需要与细胞和生长因子结合才能达到足够的治疗效果。因此，经CA - NAG处理的木材水凝胶成功地解决了当前疗法的局限性，这些疗法要么无法修复关节软骨，要么牺牲健康软骨。据我们所知，这是关于利用间伐木材进行组织工程的开创性研究，这将有助于解决全球健康和环境问题，并创建一个可持续发展的社会。
