Li Linli, Liu Xifeng, Gaihre Bipin, Park Sungjo, Li Yong, Terzic Andre, Lu Lichun
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Stem Cells Int. 2021 Aug 13;2021:1938819. doi: 10.1155/2021/1938819. eCollection 2021.
cell recruitment is a promising regenerative medicine strategy with the purpose of tissue regeneration without stem cell transplantation. This chemotaxis-based strategy is aimed at ensuring a restorative environment through the release of chemokines that promote site-specific migration of healing cell populations. Stromal cell-derived factor-1 (SDF-1) is a critical chemokine that can regulate the migration of mesenchymal stem cells (MSCs). Accordingly, here, SDF-1-loaded microporous oligo[poly(ethylene glycol) fumarate]/bis[2-(methacryloyloxy)ethyl] phosphate composites (SDF-1/OPF/BP) were engineered and probed. SDF-1/OPF/BP composites were loaded with escalating SDF-1 concentrations, namely, 0 ng/ml, 50 ng/ml, 100 ng/ml, and 200 ng/ml, and were cocultured with MSC. Scratching assay, Transwell assay, and three-dimensional migration model were utilized to assess the migration response of MSCs. Immunofluorescence staining of Runx2 and osteopontin (OPN), ELISA assay of osteocalcin (OCN) and alkaline phosphatase (ALP), and Alizarin Red S staining were conducted to assess the osteogenesis of MSCs. All SDF-1/OPF/BP composites engendered a release of SDF-1 (>80%) during the first four days. SDF-1 released from the composites significantly promoted migration and osteogenic differentiation of MSCs documented by upregulated expression of osteogenic-related proteins, ALP, Runx2, OCN, and OPN. SDF-1 at 100 ng/ml was optimal for enhanced migration and osteogenic proficiency. Thus, designed SDF-1/OPF/BP composites were competent in promoting the homing and osteogenesis of MSCs and thus offer a promising bioactive scaffold candidate for on-demand bone tissue regeneration.
细胞募集是一种很有前景的再生医学策略，其目的是在不进行干细胞移植的情况下实现组织再生。这种基于趋化作用的策略旨在通过释放趋化因子来确保修复环境，从而促进愈合细胞群体的位点特异性迁移。基质细胞衍生因子-1（SDF-1）是一种关键趋化因子，可调节间充质干细胞（MSC）的迁移。因此，在此设计并探究了负载SDF-1的微孔聚（乙二醇富马酸酯）/双[2-（甲基丙烯酰氧基）乙基]磷酸酯复合材料（SDF-1/OPF/BP）。SDF-1/OPF/BP复合材料负载有递增浓度的SDF-1，即0 ng/ml、50 ng/ml、100 ng/ml和200 ng/ml，并与MSC共培养。利用划痕试验、Transwell试验和三维迁移模型评估MSC的迁移反应。进行Runx2和骨桥蛋白（OPN）的免疫荧光染色、骨钙素（OCN）和碱性磷酸酶（ALP）的ELISA检测以及茜素红S染色，以评估MSC的成骨作用。所有SDF-1/OPF/BP复合材料在前四天内均释放出SDF-1（>80%）。复合材料释放的SDF-1通过上调成骨相关蛋白、ALP、Runx2、OCN和OPN的表达，显著促进了MSC的迁移和成骨分化。100 ng/ml的SDF-1对增强迁移和成骨能力最为理想。因此，设计的SDF-1/OPF/BP复合材料能够促进MSC的归巢和成骨，从而为按需骨组织再生提供了一种有前景的生物活性支架候选物。
