Histogenics Corporation, Waltham, MA, USA.
Sports Medicine Center, Funabashi Orthopaedic Hospital, Chiba, Japan.
Cartilage. 2021 Dec;13(2_suppl):1088S-1101S. doi: 10.1177/19476035211053837. Epub 2021 Nov 11.
Autologous chondrocyte implantation was the first cell-based therapy that used a tissue engineering process to repair cartilage defects. Recently improved approaches and tissue-engineered cell constructs have been developed for growing patient populations. We developed a chondrocyte construct using a collagen gel and sponge scaffold and physicochemical stimuli, implanted with a surgical adhesive. We conducted a proof-of-concept study of these improvements using a cartilage defect model in miniature swine.
We implanted the autologous chondrocyte constructs into full-thickness chondral defects in the femoral condyle, compared those results with empty and acellular scaffold controls, and compared implantation techniques with adhesive alone and with partial adhesive with suture. Two weeks after the creation of the defects and implantation of the cellular or acellular constructs, we arthroscopically confirmed that the implanted constructs remained at the chondral defects. We evaluated the regenerated tissue macro- and microscopically 6 months after the cell constructs were implanted. The tissues were stained with Safranin-O and evaluated using Sellers' histology grading system.
The defects implanted with processed cell constructs and acellular scaffolds were filled with chondrocyte-like round cells and with nearly normal tissue architecture that were significantly greater degree compared to empty defect control. Even with the adhesive alone and with suture alone, the cell construct was composed of the dense cartilaginous matrix that was found in the implantation using both the sutures and the adhesive.
Implantation of cell constructs promoted regeneration and integration of articular cartilage at chondral defects in swine by 6 months.
自体软骨细胞移植是第一种采用组织工程学方法修复软骨缺损的细胞治疗方法。最近,为了满足不断增长的患者群体的需求,已经开发出了改进的方法和组织工程细胞构建体。我们使用胶原凝胶和海绵支架以及物理化学刺激物开发了一种软骨细胞构建体,并使用手术粘合剂进行植入。我们使用小型猪的软骨缺损模型对这些改进进行了概念验证研究。
我们将自体软骨细胞构建体植入股骨髁的全层软骨缺损中,将结果与空支架和无细胞支架对照进行比较,并将植入技术与单独使用粘合剂以及与缝线结合使用部分粘合剂进行比较。在创建缺陷和植入细胞或无细胞构建体后两周,我们通过关节镜确认植入的构建体仍位于软骨缺陷处。在细胞构建体植入 6 个月后,我们对再生组织进行了宏观和微观评估。使用 Safranin-O 对组织进行染色,并使用 Sellers 组织学分级系统进行评估。
与空缺陷对照相比,用处理后的细胞构建体和无细胞支架植入的缺陷充满了类似于软骨细胞的圆形细胞,并且具有几乎正常的组织结构,程度显著更高。即使单独使用粘合剂或单独使用缝线,细胞构建体也由在使用缝线和粘合剂的植入物中发现的致密软骨基质组成。
在 6 个月时,细胞构建体的植入促进了猪软骨缺损处关节软骨的再生和整合。