Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College St., Toronto, Ontario M5S 3G9, Canada.
Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College St., Toronto, Ontario M5S 3G9, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada.
Acta Biomater. 2017 Oct 15;62:352-361. doi: 10.1016/j.actbio.2017.08.016. Epub 2017 Aug 14.
Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates.
Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this organization using isolated deep zone cartilage cells and a sol-gel hydroxyapatite coated bone substitute material composed of calcium polyphosphate (CPP). Developing a layer of calcified cartilage at the interface should contribute to enhancing the success of this "osteochondral-like" construct following implantation to repair cartilage defects.
将体外形成的软骨整合到合适的基质上,形成组织工程植入物来修复骨软骨缺损是一个相当大的挑战。在健康的软骨中,钙化软骨区 (ZCC) 充当从软组织到硬组织传递机械力的中间物,以及一种有效的互锁结构,以更好地抵抗界面剪切力。我们开发了双相构建体,这些构建体由在多孔磷酸钙多聚体 (CPP) 基质上体外生长并相互交织的无支架软骨组织组成。然而,随着 CPP 的降解,它会释放出无机多磷酸盐 (polyP),从而抑制局部矿化,从而防止在界面处形成 ZCC。因此,我们假设在 CPP 基底上涂覆一层羟基磷灰石 (HA) 可能会防止或限制这种 polyP 释放。为了研究这一点,我们测试了无机或有机溶胶-凝胶处理方法,作为 CPP 基底的阻挡涂层以抑制 polyP 释放。这两种类型的涂层都支持与基底直接接触的 ZCC 的形成,然而,在有机 HA 溶胶凝胶涂覆的 CPP 上形成的组织中,ZCC 似乎更连续。涂覆基底上形成的组织积累了相当数量的细胞外基质和矿物质,但在有机溶胶-凝胶 (OSG) 涂覆基底上形成的组织积累的 polyP 少于在无机溶胶-凝胶 (ISG) 涂覆基底上形成的组织。用 OSG 涂覆 CPP 基底形成的构建体具有比用 ISG 涂覆和未涂覆基底形成的构建体更大的界面剪切强度。这些结果表明,OSG 涂层方法可以改变 ZCC 的位置和分布,并可用于改善在多孔 CPP 基底上形成的组织工程构建体的机械完整性。
关节软骨与骨骼通过钙化软骨区相连。本研究描述了一种使用分离的深区软骨细胞和由磷酸钙多聚体 (CPP) 组成的溶胶-凝胶羟基磷灰石涂覆的骨替代材料生成模拟这种组织的“骨软骨样”植入物的方法。在界面处形成一层钙化软骨应该有助于增强这种“骨软骨样”构建体在植入以修复软骨缺陷后的成功。