Generally, the thickness of tubular tissues formed from silicone rods through encapsulation of the foreign–body reaction is less than approximately 0.2 mm. On the other hand, it is unclear how hollow cylindrical molds can provide thick tubular tissues, known as Biotubes, with a thickness exceeding 1 mm, during in-body tissue architecture (iBTA) using encapsulation. In this study, histological and structural analyses were performed to understand the reason for the formation of thick mold-based Biotubes. Molds were assembled with a gap between a silicone rod and a stainless-steel cylinder and were embedded into the dorsal subcutaneous pouches of beagles for 2 or 4 weeks. Thick Biotubes were obtained from the harvested mold. The histological analysis showed that the lumen side of the thick Biotubes consisted primarily of type I collagen fibers and α-smooth muscle actin-positive cells, similar to the original rod-based thin Biotubes formed only from silicone rods. Interestingly, the outer region of the thick Biotubes was an immature connective tissue consisting of type III collagen, including primitive somatic stem cells expressing CD90 and SSEA4. These stem cells may have contributed to the formation of the thick-walled Biotubes by differentiating into other cell types and through growth factor production. Because of the potential tissue-repair ability of these stem cells, iBTA could be useful for elucidating the regeneration process, remodeling the physiology/pathology of tissue defects/damage, and cell acquisition. This technology can provide autologous stem cells without in vitro cell culture. Moreover, thick-walled Biotubes may be useful as an alternative stem cell-containing material in regenerative medicine.

通常，硅胶棒通过包裹异物反应形成的管状组织的厚度小于约 0.2 毫米。另一方面，在使用封装的体内组织结构 (iBTA) 期间，中空圆柱形模具如何提供厚度超过 1 毫米的厚管状组织（称为生物管）尚不清楚。在这项研究中，进行了组织学和结构分析，以了解形成厚模具生物管的原因。用硅胶棒和不锈钢圆柱体之间的间隙组装模具，并嵌入比格犬的背部皮下囊中 2 或 4 周。从收获的霉菌中获得厚生物管。组织学分析表明，粗 Biotubes 的管腔侧主要由 I 型胶原纤维和 α-平滑肌肌动蛋白阳性细胞组成，类似于仅由硅胶棒形成的原始杆状薄 Biotubes。有趣的是，厚生物管的外部区域是由 III 型胶原蛋白组成的未成熟结缔组织，包括表达 CD90 和 SSEA4 的原始体干细胞。这些干细胞可能通过分化为其他细胞类型和通过产生生长因子而促进了厚壁生物管的形成。由于这些干细胞具有潜在的组织修复能力，iBTA 可用于阐明再生过程、重塑组织缺陷/损伤的生理学/病理学以及细胞获取。该技术无需体外细胞培养即可提供自体干细胞。此外，厚壁生物管可用作再生医学中含有干细胞的替代材料。