Background

Injury to articular cartilage cause certain degree of disability due to poor self-repair ability of cartilage tissue. To promote cartilage regeneration, it is essential to develop a scaffold that properly mimics the native cartilage extracellular matrix (ECM) in the aspect of compositions and functions.

Methods

A mussel-inspired strategy was developed to construct an ECM-mimicking hydrogel scaffold by incorporating polydopamine-modified hyaluronic acid (PDA/HA) complex into a dual-crosslinked collagen (Col) matrix for growth factor-free cartilage regeneration. The adhesion, proliferation, and chondrogenic differentiation of cells on the scaffold were examined. A well-established full-thickness cartilage defect model of the knee in rabbits was used to evaluated the efficacy and functionality of the engineered Col/PDA/HA hydrogel scaffold.

Results

The PDA/HA complex incorporated-hydrogel scaffold with catechol moieties exhibited better cell affinity than bare negatively-charged HA incorporated hydrogel scaffold. In addition, the PDA/HA complex endowed the scaffold with immunomodulation ability, which suppressed the expression of inflammatory cytokines and effectively activated the polarization of macrophages toward M2 phenotypes. The in vivo results revealed that the mussel-inspired Col/PDA/HA hydrogel scaffold showed strong cartilage inducing ability to promote cartilage regeneration.

Conclusions

The PDA/HA complex-incorporated hydrogel scaffold overcame the cell repellency of negatively-charged polysaccharide-based scaffolds, which facilitated the adhesion and clustering of cells on the scaffold, and therefore enhanced cell-HA interactions for efficient chondrogenic differentiation. Moreover, the hydrogel scaffold modulated immune microenvironment, and created a regenerative microenvironment to enhance cartilage regeneration.

The translational potential of this article

This study gives insight into the mussel-inspired approach to construct the tissue-inducing hydrogel scaffold in a growth-factor-free manner, which show great advantage in the clinical treatment. The hydrogel scaffold composed of collagen and hyaluronic acid as the major component, providing cartilage ECM-mimicking environment, is promising for cartilage defect repair.

中文翻译：

---

受贻贝启发的细胞外基质模拟水凝胶支架具有高细胞亲和力和免疫调节能力，可用于无生长因子的软骨再生

背景

关节软骨损伤由于软骨组织自身修复能力差，导致一定程度的残疾。为了促进软骨再生，必须开发一种在成分和功能方面适当模仿天然软骨细胞外基质 (ECM) 的支架。

方法

开发了一种受贻贝启发的策略，通过将聚多巴胺修饰的透明质酸 (PDA/HA) 复合物掺入双交联胶原 (Col) 基质中来构建模拟 ECM 的水凝胶支架，用于无生长因子的软骨再生。检查了支架上细胞的粘附、增殖和成软骨分化。使用完善的兔膝全层软骨缺损模型来评估工程化 Col/PDA/HA 水凝胶支架的功效和功能。

结果

具有儿茶酚部分的 PDA/HA 复合物结合水凝胶支架表现出比裸带负电荷的 HA 结合水凝胶支架更好的细胞亲和力。此外，PDA/HA复合物赋予支架免疫调节能力，抑制炎性细胞因子的表达，有效激活巨噬细胞向M2表型的极化。体内结果表明，受贻贝启发的 Col/PDA/HA 水凝胶支架具有很强的软骨诱导能力，可促进软骨再生。

结论

PDA/HA复合水凝胶支架克服了带负电荷的多糖基支架的细胞排斥性，促进了细胞在支架上的粘附和聚集，从而增强了细胞-HA的相互作用，从而实现有效的软骨分化。此外，水凝胶支架可调节免疫微环境，创造再生微环境以增强软骨再生。

本文的翻译潜力

本研究深入了解了以贻贝为灵感的方法以无生长因子的方式构建组织诱导水凝胶支架，在临床治疗中显示出巨大优势。以胶原蛋白和透明质酸为主要成分的水凝胶支架，提供软骨细胞外基质模拟环境，有望修复软骨缺损。