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Bio-Design and Manufacturing  2026 Vol.9 No.1 P.122 - 136

http://doi.org/10.1631/bdm.2500291


Bioextrusion of hydrogels with controlled mineral gradients for regenerative engineering of osteochondral interfaces


Author(s):  Xiao Zhao, Weiwei Wang, Xiaojun Yu, Dilhan M. Kalyon, Cevat Erisken

Affiliation(s):  1. Department of Chemical Engineering and Materials Science, Charles V. Schaefer, Jr. School of Engineering & Science, Stevens Institute of Technology, Hoboken, NJ, 07030, USA more

Corresponding email(s):   dkalyon@stevens.edu, dkalyon@stevens.edu

Key Words:  Osteochondral (OC) interface, Mineral gradient, Bioextrusion, Hydrogel scaffold, Regenerative engineering


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Xiao Zhao. Bioextrusion of hydrogels with controlled mineral gradients for regenerative engineering of osteochondral interfaces[J]. Journal of Zhejiang University Science D, 2026, 9(1): 122 - 136.

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Abstract: 
The osteochondral (OC) interface exhibits a mineral gradient, varying in thickness by several hundred micrometers across different species. Disruptions in this interface damage OC tissues, leading to osteoarthritis. The natural architecture and composition of native OC interfaces can be replicated using biomaterial scaffolds via regenerative engineering approaches. A novel one-step bioextrusion process was employed to fabricate a unitary synthetic graft (USG), which mimics the native OC interfaces mineral concentration gradient. This novel USG is composed of an agarose-based cartilage layer and a bone layer, consisting of agarose enriched with 20% (200 g/L) hydroxyapatite. The USG features a gradient interface with mineral concentrations transitioning from 0% to 20% (mass fraction), mimicking the transition between the cartilage and bone. Thermogravimetric analysis revealed that the gradient transition lengths of the graft and native OC tissue harvested from bovine knees were similar ((64721) vs. (633124) m). The linear viscoelastic properties of the grafts, which were evaluated using strain sweep and frequency sweep tests with oscillatory shear, indicated a dominant storage modulus over loss modulus similar to that of native OC tissues. The compressive and stress relaxation behaviors of the USGs demonstrated that the graft maintained structural integrity under mechanical stress. Viability assays performed after bioextrusion showed that chondrocytes and human fetal osteoblast cells successfully integrated and survived within their designated regions of the graft. The novel USGs exhibit properties similar to native OC tissue and are promising candidates for regenerating OC defects and restoring knee joint functionality.

Bioextrusion of hydrogels with controlled mineral gradients for regenerative engineering of osteochondral interfaces

骨软骨 (OC) 界面存在矿物质含量梯度, 其厚度在不同物种中可达数百微米。 当该界面受到破坏时, 骨软骨组织功能受损, 进而诱发骨关节炎 (OA)。 通过再生工程, 可利用仿生生物材料支架重建 OC 界面的天然结构与成分。 本研究提出一种新型一步生物挤出工艺, 构建单体型合成移植物 (USG), 模拟天然 OC 界面的矿物梯度。 该 USG 由琼脂糖基软骨层以及含 200 g/L 羟基磷灰石的琼脂糖骨层构成, 界面区域形成从 0% 至 20% (质量分数) 连续变化的矿物梯度, 以仿生软骨向骨组织的过渡。 热重分析表明, USG 的梯度区长度与牛膝关节 OC 组织相近 ((647±21) µm vs. (633±124) µm)。 在振荡剪切条件下进行的应变扫描与频率扫描测试表明, USG 表现出与天然 OC 组织一致的黏弹特征, 其储能模量始终高于损耗模量。 压缩与应力松弛实验表明, USG 在机械载荷下保持良好的结构完整性。 生物挤出后的细胞活性检测结果显示, 软骨细胞与人胎源性成骨细胞在预设区域内实现成功驻留与存活。 综上所述, 该新型 USG 在结构与力学行为方面均接近天然 OC 组织, 是修复骨软骨缺损、 恢复膝关节功能的潜在候选材料。
Osteochondral (OC) interface; Mineral gradient; Bioextrusion; Hydrogel scaffold; Regenerative engineering

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