Biomedical Engineering Department, Northwestern University, Evanston, Illinois 60208, USA.
Tissue Eng Part C Methods. 2012 Feb;18(2):113-21. doi: 10.1089/ten.TEC.2011.0289. Epub 2011 Dec 22.
Scaffolds for tissue engineering applications must incorporate porosity for optimal cell seeding, tissue ingrowth, and vascularization, but common fabrication methods for achieving porosity are incompatible with a variety of polymers, limiting widespread use. In this study, porous scaffolds consisting of poly(1,8-octanediol-co-citrate) (POC) containing hydroxyapatite nanocrystals (HA) were fabricated using low-pressure foaming (LPF). LPF is a novel method of fabricating an interconnected, porous scaffold with relative ease. LPF takes advantage of air bubbles that act as pore nucleation sites during a polymer mixing step. Vacuum is applied to expand the nucleation sites into interconnected pores that are stabilized through cross-linking. POC was combined with 20%, 40%, and 60% by weight HA, and the effect of increasing HA particle content on porosity, mechanical properties, and alkaline phosphatase (ALP) activity of human mesenchymal stem cells (hMSC) was evaluated. The effect of the prepolymer viscosity on porosity and the mechanical properties of POC with 40% by weight HA (POC-40HA) were also assessed. POC-40HA scaffolds were also implanted in an osteochondral defect of a rabbit model, and the explants were assessed at 6 weeks using histology. With increasing HA content, the pore size of POC-HA scaffolds can be varied (85 to 1,003 μm) and controlled to mimic the pore size of native trabecular bone. The compression modulus increased with greater HA content under dry conditions and were retained to a greater extent than with porous scaffolds fabricated using salt-leaching under wet conditions. Furthermore, all POC-HA scaffolds prepared using LPF supported hMSC attachment, and an increase in ALP activity correlated with an increase in HA content. An increase in the prepolymer viscosity resulted in increased compression modulus, greater distance between pores, and less porosity. After 6 weeks in vivo, cell and tissue infiltration was present throughout the scaffold. This study describes a novel method of creating porous osteoconductive POC scaffolds without the need for porogen leaching and provides the groundwork for applying LPF to other elastomers and composites.
用于组织工程应用的支架必须具有多孔性以实现最佳细胞接种、组织长入和血管化,但常见的实现多孔性的制造方法与各种聚合物不兼容,限制了其广泛应用。在这项研究中,使用低压发泡(LPF)制造了包含羟基磷灰石纳米晶体(HA)的聚(1,8-辛二醇-co-柠檬酸)(POC)多孔支架。LPF 是一种新颖的制造具有相对容易的互连多孔支架的方法。LPF 利用聚合物混合步骤中充当孔成核点的气泡。施加真空将成核点扩展成通过交联稳定的互连孔。将 POC 与 20%、40%和 60%重量的 HA 结合,并评估增加 HA 颗粒含量对多孔性、机械性能和碱性磷酸酶(ALP)活性的影响人类间充质干细胞(hMSC)。还评估了预聚物粘度对 POC 中 40%重量 HA(POC-40HA)的多孔性和机械性能的影响。还将 POC-40HA 支架植入兔模型的骨软骨缺损中,并在 6 周时使用组织学进行评估。随着 HA 含量的增加,POC-HA 支架的孔径可以变化(85 至 1,003μm)并进行控制以模拟天然小梁骨的孔径。在干燥条件下,随着 HA 含量的增加,压缩模量增加,并且比在湿条件下使用盐浸出制造的多孔支架保留的程度更大。此外,使用 LPF 制备的所有 POC-HA 支架都支持 hMSC 附着,并且 ALP 活性的增加与 HA 含量的增加相关。预聚物粘度的增加导致压缩模量增加、孔之间的距离增加和孔隙率降低。在体内 6 周后,细胞和组织渗透存在于整个支架中。本研究描述了一种制造具有骨诱导性的多孔 POC 支架而无需进行造孔剂浸出的新方法,并为将 LPF 应用于其他弹性体和复合材料奠定了基础。