Department of Orthopedics Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, People's Republic of China; Department of Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
Department of Radiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, People's Republic of China.
Acta Biomater. 2018 Apr 15;71:496-509. doi: 10.1016/j.actbio.2018.03.019. Epub 2018 Mar 16.
Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Although adipose-derived stem cell (ADSC)-based therapy is regarded to be promising for the treatment of degenerated NP, there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. The induction effect of the scaffold on ADSC differentiation was studied in vitro, and a rat coccygeal vertebrae degeneration model was used to investigate the regenerative effect of the CCSA system on the degenerated NP in vivo. The results showed that the CCSA delivery system cross-linked with 0.02% genipin was biocompatible and promoted the expressions of NP-specific genes. After the injection of the CCSA system, the disc height, water content, extracellular matrix synthesis, and structure of the degenerated NP were partly restored. Our CCSA delivery system uses minimally invasive approaches to promote the regeneration of degenerated NP and provides an exciting new avenue for the treatment of degenerative disc disease.
Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Stem cell-based tissue engineering is a promising method in NP regeneration, but there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. Although several research groups have studied the fabrication of injectable hydrogel with biological matrix, our study differs from other works. We chose type II collagen and CS, the two primary native components in the NP, as the main materials and combined them according to the natural ratio of collagen and sGAG in the NP. The delivery system is preloaded with ADSCs and can be injected into the NP with a needle, followed by in situ gelation. Genipin is used as a cross-linker to improve the bio-stability of the scaffold, with low cytotoxicity. We investigated the stimulatory effects of our scaffold on the differentiation of ADSCs in vitro and the regenerative effect of the CCSA delivery system on degenerated NP in vivo.
椎间盘退变通常起源于髓核（NP）退变，进而导致下腰痛。尽管基于脂肪来源干细胞（ADSC）的治疗方法被认为是治疗退变 NP 的有前途的方法，但缺乏可行的细胞载体将 ADSCs 移植到 NP 中，同时保持细胞功能。在这项研究中，我们开发了一种以京尼平为交联剂的 II 型胶原/硫酸软骨素（CS）复合水凝胶样 ADSC（CCSA）递药系统。体外研究了支架对 ADSC 分化的诱导作用，并用大鼠尾骨椎骨退变模型研究了 CCSA 系统对退变 NP 的体内再生作用。结果表明，用 0.02%京尼平交联的 CCSA 递药系统具有生物相容性，并促进了 NP 特异性基因的表达。注射 CCSA 系统后，部分恢复了退变 NP 的椎间盘高度、含水量、细胞外基质合成和结构。我们的 CCSA 递药系统采用微创方法促进退变 NP 的再生，为治疗退行性椎间盘疾病提供了令人兴奋的新途径。
椎间盘（NP）退变通常是椎间盘退变和随后下腰痛的起源。基于干细胞的组织工程是 NP 再生的一种很有前途的方法，但缺乏可行的细胞载体将 ADSCs 移植到 NP 中，同时保持细胞功能。在这项研究中，我们开发了一种以京尼平为交联剂的 II 型胶原/硫酸软骨素（CS）复合水凝胶样 ADSC（CCSA）递药系统。尽管有几个研究小组研究了用生物基质制备可注射水凝胶，但我们的研究与其他工作不同。我们选择 II 型胶原和 CS，这两种 NP 的主要天然成分，作为主要材料，并根据 NP 中胶原和 sGAG 的天然比例将它们结合在一起。该递药系统预先加载 ADSCs，并用针将其注入 NP，然后原位凝胶化。京尼平用作交联剂，以提高支架的生物稳定性，细胞毒性低。我们研究了支架对 ADSC 体外分化的刺激作用，以及 CCSA 递药系统对体内退变 NP 的再生作用。
