Directorate of Combat Casualty Care & Operational Medicine, Naval Medical Research Unit San Antonio, San Antonio, Texas, USA.
Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
J Biomed Mater Res B Appl Biomater. 2022 Sep;110(9):2063-2074. doi: 10.1002/jbm.b.35061. Epub 2022 Mar 28.
Trauma-induced, critical-size bone defects pose a clinical challenge to heal. Albeit autografts are the standard-of-care, they are limited by their inability to be shaped to various defect geometries and often incur donor site complications. Herein, the combination of a "self-fitting" shape memory polymer (SMP) scaffold and seeded mesenchymal stromal cells (MSCs) was investigated as an alternative. The porous SMP scaffold, prepared from poly(ε-caprolactone) diacrylate (PCL-DA) and coated with polydopamine, provided conformal shaping and cell adhesion. MSCs from five tissues, amniotic (AMSCs), chorionic tissue (CHSCs), umbilical cord (UCSCs), adipose (ADSCs), and bone marrow (BMSCs) were evaluated for viability, density, and osteogenic differentiation on the SMP scaffold. BMSCs exhibited the fastest increase in cell density by day 3, but after day 10, CHSCs, UCSCs, and ADSCs approached similar cell density. BMSCs also showed the greatest calcification among the cell types, followed closely by ADSCs, CHSCs and AMSCs. Alkaline phosphatase (ALP) activity peaked at day 7 for AMSCs, UCSCs, ADSCs and BMSCs, and at day 14 for CHSCs, which had the greatest overall ALP activity. Of all the cell types, only scaffolds cultured with ADSCs in osteogenic media had increased hardness and local modulus as compared to blank scaffolds after 21 days of cell culture and osteogenic differentiation. Overall, ADSCs performed most favorably on the SMP scaffold. The SMP scaffold was able to support key cellular behaviors of MSCs and could potentially be a viable, regenerative alternative to autograft.
创伤诱导的临界尺寸骨缺损对愈合构成临床挑战。尽管自体移植物是标准的治疗方法,但它们受到无法适应各种缺损几何形状的限制,并且常常引起供体部位并发症。在此,研究了“自适配”形状记忆聚合物(SMP)支架和接种间充质基质细胞(MSCs)的组合作为替代方法。多孔 SMP 支架由聚(ε-己内酯)二丙烯酸酯(PCL-DA)制备,并涂有聚多巴胺,提供了贴合的形状和细胞附着。评估了来自五种组织(羊膜(AMSCs)、绒毛膜组织(CHSCs)、脐带(UCSCs)、脂肪(ADSCs)和骨髓(BMSCs)的 MSCs 在 SMP 支架上的活力、密度和成骨分化。BMSCs 在第 3 天表现出细胞密度的最快增加,但在第 10 天后,CHSCs、UCSCs 和 ADSCs 接近相似的细胞密度。BMSCs 还表现出所有细胞类型中最大的钙化,紧随其后的是 ADSCs、CHSCs 和 AMSCs。碱性磷酸酶(ALP)活性在第 7 天达到 AMSCs、UCSCs、ADSCs 和 BMSCs 的峰值,在第 14 天达到 CHSCs 的峰值,其总 ALP 活性最高。在所有细胞类型中,只有在成骨培养基中培养的 ADSCs 支架在细胞培养和成骨分化 21 天后与空白支架相比具有增加的硬度和局部模量。总体而言,ADSCs 在 SMP 支架上表现最好。SMP 支架能够支持 MSCs 的关键细胞行为,并且可能是自体移植物的可行的再生替代方法。