Department of Life Science Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria.
Austrian Cluster for Tissue Regeneration, Vienna, Austria.
Am J Sports Med. 2019 Mar;47(3):620-627. doi: 10.1177/0363546518818792. Epub 2019 Jan 17.
Given the unsatisfactory results and reported drawbacks of anterior cruciate ligament (ACL) reconstruction, such as donor site morbidity and the limited choice of grafts in revision surgery, new regenerative approaches based on tissue-engineering strategies are currently under investigation.
To determine (1) if a novel silk fiber-based ACL scaffold is able to initiate osteointegration in the femoral and tibial bone tunnels under in vivo conditions and (2) if the osteointegration process will be improved by intraoperatively seeding the scaffolds with the autologous stromal vascular fraction, an adipose-derived, stem cell-rich isolate from knee fat pads.
Controlled laboratory study.
A total of 33 sheep underwent ACL resection and were then randomly assigned to 2 experimental groups: ACL reconstruction with a scaffold alone and ACL reconstruction with a cell-seeded scaffold. Half of the sheep in each group were randomly chosen and euthanized 6 months after surgery and the other half at 12 months. To analyze the integration of the silk-based scaffold in the femoral and tibial bone tunnels, hard tissue histology and micro-computed tomography measurements were performed.
Hard tissue histological workup showed that in all treatment groups, with or without the application of the autologous stromal vascular fraction, an interzone of collagen fibers had formed between bone and silk-based graft. This collagen-fiber continuity partly consisted of Sharpey fibers, comparable with tendon-bone healing known for autografts and allografts. Insertion sites were more broad based at 6 months and more concentrated on the slightly protruding, bony knoblike structures at 12 months. Histologically, no differences between the treatment groups were detectable. Analysis of micro-computed tomography measurements revealed a significantly higher tissue density for the cell-seeded scaffold group as compared with the scaffold-alone group in the tibial but not femoral bone tunnel after 12 months of implantation.
The novel silk fiber-based scaffold for ACL regeneration demonstrated integration into the bone tunnels via the formation of a fibrous interzone similar to allografts and autografts. Histologically, additional cell seeding did not enhance osteointegration. No significant differences between 6 and 12 months could be detected. After 12 months, there was still a considerable amount of silk present, and a longer observation period is necessary to see if a true ligament-bone enthesis will be formed.
ACL regeneration with a silk fiber-based scaffold with and without additional cell seeding may provide an alternative treatment option to current techniques of surgical reconstruction.
由于前交叉韧带（ACL）重建的结果不理想，且存在一些缺点，例如供体部位发病率高，以及在翻修手术中可供选择的移植物有限，因此目前正在研究基于组织工程策略的新型再生方法。
确定（1）新型丝纤维 ACL 支架在体内条件下是否能够在股骨和胫骨骨隧道中启动骨整合，以及（2）术中用自体基质血管成分（从膝关节脂肪垫中提取的富含干细胞的脂肪来源分离物）接种支架是否会改善骨整合过程。
对照实验室研究。
33 只绵羊接受 ACL 切除术，然后随机分为 2 个实验组：仅用支架重建 ACL 和用细胞接种的支架重建 ACL。每组中有一半的绵羊随机选择，并在手术后 6 个月和 12 个月时安乐死。为了分析丝基支架在股骨和胫骨骨隧道中的整合情况，进行了硬组织组织学和微计算机断层扫描测量。
硬组织组织学研究表明，在所有治疗组中，无论是否应用自体基质血管成分，骨与丝基移植物之间都形成了胶原纤维的过渡区。这种胶原纤维连续性部分由Sharpey 纤维组成，与自体移植物和同种异体移植物的肌腱-骨愈合相当。6 个月时，插入部位更宽，12 个月时更集中在略微突出的、骨状的小结节结构上。组织学上，各组之间没有差异。微计算机断层扫描测量分析显示，与单独使用支架组相比，在胫骨骨隧道中，细胞接种支架组在植入 12 个月后的组织密度显著更高。
新型丝纤维 ACL 再生支架通过形成类似于同种异体和自体移植物的纤维过渡区，整合到骨隧道中。组织学上，额外的细胞接种并没有增强骨整合。在 6 个月和 12 个月之间没有发现显著差异。12 个月后，仍有大量的丝存在，需要更长的观察期才能确定是否会形成真正的韧带-骨结合。
使用丝纤维基支架进行 ACL 再生，无论是否附加细胞接种，都可能为目前的手术重建技术提供一种替代治疗选择。
