Department of Oral and Maxillofacial Surgery, Hannover Medical School, Hannover, Germany.
Tissue Eng Part A. 2010 Jul;16(7):2265-79. doi: 10.1089/ten.TEA.2008.0457.
Bone substitutes should ideally promote rapid vascularization, which could be accelerated if these substitutes were vitalized by autologous cells. Although adequate engraftment of porous poly(L-lactide-co-glycolide) (PLGA) scaffolds has been demonstrated in the past, it has not yet been investigated how vascularization is influenced by vitalization or, more precisely, by seeding PLGA scaffolds with osteoblast-like cells (OLCs). For this reason, we conducted an in vivo study to assess host angiogenic and inflammatory responses after the implantation of PLGA scaffolds vitalized with isogeneic OLCs.
OLCs were seeded on collagen-coated PLGA scaffolds that were implanted into dorsal skinfold chambers in BALB/c mice (n = 8). Two further groups of animals received either collagen-coated (n = 8) or uncoated PLGA scaffolds (n = 8). Animals that received chambers without implants served as controls (n = 8). Angiogenesis, neovascularization, and leukocyte-endothelial cell interaction were analyzed for 14 days using intravital fluorescence microscopy.
PLGA scaffolds with and without OLCs showed a temporary increase in leukocyte recruitment. At day 3 after implantation, a marked angiogenic host tissue response was observed in close vicinity of all scaffolds studied. At days 6 and 10, the angiogenic response was significantly higher (p < 0.05) in PLGA scaffolds vitalized with OLCs than in uncoated or collagen-coated PLGA scaffolds. The majority of OLCs, however, died within 14 days after implantation.
Our study demonstrates that PLGA scaffold vitalization with OLCs accelerates the angiogenic response in the surrounding host tissue. Bone substitutes created by tissue engineering may thus be superior to nonvitalized substitutes although the seeded cells do not survive for long periods.
理想情况下，骨替代物应能促进快速血管生成，如果这些替代物被自体细胞激活，其血管生成速度可能会加快。虽然过去已经证明多孔聚（L-丙交酯-共-乙交酯）（PLGA）支架的充分植入，但尚未研究血管生成如何受到激活的影响，或者更确切地说，如何通过将成骨样细胞（OLC）接种到 PLGA 支架上来影响血管生成。出于这个原因，我们进行了一项体内研究，以评估植入同种异体 OLC 激活的 PLGA 支架后宿主的血管生成和炎症反应。
将 OLC 接种在胶原蛋白涂覆的 PLGA 支架上，然后将其植入 BALB/c 小鼠背部皮褶室（n = 8）。另外两组动物分别接受胶原蛋白涂覆的（n = 8）或未涂覆的 PLGA 支架（n = 8）。接受无植入物的腔室的动物作为对照（n = 8）。在植入后 14 天内，使用活体荧光显微镜分析血管生成、新生血管形成和白细胞-内皮细胞相互作用。
有和没有 OLC 的 PLGA 支架均显示出白细胞募集的暂时增加。在植入后第 3 天，所有研究支架附近均观察到明显的血管生成宿主组织反应。在第 6 和 10 天，OLC 激活的 PLGA 支架的血管生成反应明显高于未涂覆或胶原蛋白涂覆的 PLGA 支架（p < 0.05）。然而，大多数 OLC 在植入后 14 天内死亡。
我们的研究表明，用 OLC 激活 PLGA 支架可加速周围宿主组织的血管生成反应。虽然接种细胞不能长期存活，但通过组织工程创建的骨替代物可能优于非激活替代物。
