Zhang Zhiqiang, Li Haodong, Qian Manning, Zheng Yiming, Bao Luhan, Cui Wenguo, Wang Dahui
Department of Orthopedics, National Children's Medical Center & Children's Hospital of Fudan University, Shanghai 201102, P. R. China.
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
Regen Biomater. 2025 Jan 23;12:rbaf004. doi: 10.1093/rb/rbaf004. eCollection 2025.
The growth plate is crucial for skeletal growth in children, but research on repairing growth plate damage and restoring growth is limited. Here, a high-toughness adaptive dual-crosslinked hydrogel is designed to mimic the growth plate's structure, supporting regeneration and bone growth. Composed of aldehyde-modified bacterial cellulose (DBNC), methacrylated gelatin (GelMA) and sodium alginate (Alg), the hydrogel is engineered through ionic bonding and Schiff base reactions, creating a macroporous structure. This structure can transform into a denser form by binding with calcium ions. , the loose macroporous structure of the hydrogels can promote chondrogenic differentiation, and when it forms a dense structure by binding with calcium ions, it also can activate relevant chondrogenic signaling pathways under the influence of insulin-like growth factor I (IGF-1), further inhibiting osteogenesis. experiments in a rat model of growth plate injury demonstrated that the hydrogel promoted growth plate cartilage regeneration and minimized bone bridge formation by creating a hypoxic microenvironment that activates IGF-1-related pathways. This environment encourages chondrogenic differentiation while preventing the undesired formation of bone tissue within the growth plate area. Overall, the dual-crosslinked hydrogel not only mimics the growth plate's structure but also facilitates localized IGF-1 expression, effectively reshaping the growth plate's function. This approach represents a promising therapeutic strategy for treating growth plate injuries, potentially addressing challenges associated with skeletal growth restoration in pediatric patients.
生长板对儿童骨骼生长至关重要,但关于修复生长板损伤和恢复生长的研究有限。在此,设计了一种高韧性自适应双交联水凝胶来模拟生长板结构,支持再生和骨骼生长。该水凝胶由醛基修饰的细菌纤维素(DBNC)、甲基丙烯酸化明胶(GelMA)和海藻酸钠(Alg)组成,通过离子键和席夫碱反应构建而成,形成了大孔结构。这种结构可通过与钙离子结合转变为更致密的形式。水凝胶的疏松大孔结构可促进软骨形成分化,当它与钙离子结合形成致密结构时,在胰岛素样生长因子I(IGF-1)影响下还能激活相关软骨形成信号通路,进一步抑制成骨作用。生长板损伤大鼠模型实验表明,该水凝胶通过营造激活IGF-1相关通路的低氧微环境,促进了生长板软骨再生,并使骨桥形成最小化。这种环境促进软骨形成分化,同时防止生长板区域内不期望的骨组织形成。总体而言,双交联水凝胶不仅模拟了生长板结构,还促进了局部IGF-1表达,有效重塑了生长板功能。这种方法代表了一种治疗生长板损伤的有前景的治疗策略,可能解决儿科患者骨骼生长恢复相关的挑战。