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Investigation of multiphasic 3D-bioplotted scaffolds for site-specific chondrogenic and osteogenic differentiation of human adipose-derived stem cells for osteochondral tissue engineering applications.
Journal of Biomedical Materials Research Part B: Applied Biomaterials ( IF 3.2 ) Pub Date : 2019-12-27 , DOI: 10.1002/jbm.b.34542
Liliana F Mellor 1 , Rachel C Nordberg 1, 2 , Pedro Huebner 3 , Mahsa Mohiti-Asli 1 , Michael A Taylor 1 , William Efird 4 , Julia T Oxford 5 , Jeffrey T Spang 4 , Rohan A Shirwaiker 1, 3 , Elizabeth G Loboa 2
Affiliation  

Osteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site‐specific osteogenic and chondrogenic differentiation of human adipose‐derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using 3D‐bioplotting of biodegradable polycraprolactone (PCL) with either β‐tricalcium phosphate (TCP) or decellularized bovine cartilage extracellular matrix (dECM) to drive site‐specific hASC osteogenesis and chondrogenesis, respectively. PCL‐dECM scaffolds demonstrated elevated matrix deposition and organization in scaffolds seeded with hASC as well as a reduction in collagen I gene expression. 3D‐bioplotted PCL scaffolds with 20% TCP demonstrated elevated calcium deposition, endogenous alkaline phosphatase activity, and osteopontin gene expression. Osteochondral scaffolds comprised of hASC‐seeded 3D‐bioplotted PCL‐TCP, electrospun PCL, and 3D‐bioplotted PCL‐dECM phases were evaluated and demonstrated site‐specific osteochondral tissue characteristics. This technique holds great promise as cartilage morbidity is minimized since autologous cartilage harvest is not required, tissue rejection is minimized via use of an abundant and accessible source of autologous stem cells, and biofabrication techniques allow for a precise, customizable methodology to rapidly produce the scaffold.

中文翻译:

研究用于骨软骨组织工程应用的人脂肪干细胞位点特异性软骨形成和成骨分化的多相 3D 生物标绘支架。

骨关节炎是一种退行性关节疾病,由于关节软骨和软骨下骨的退化,限制了受影响关节的活动能力。当试图修复或逆转软骨退化的影响时,软骨有限的再生能力提出了重大挑战。组织工程医疗产品是治疗骨软骨变性的有前途的替代品,因为它们有可能融入患者现有的组织中。本研究的目标是创建一种支架,可以诱导人脂肪干细胞 (hASC) 的位点特异性成骨和软骨分化,以产生完整的骨软骨植入物。支架是使用可生物降解的聚克拉内酯 (PCL) 与 β-磷酸三钙 (TCP) 或脱细胞牛软骨细胞外基质 (dECM) 的 3D 生物绘图制造的,以分别驱动位点特异性 hASC 成骨和软骨形成。PCL-dECM 支架在接种 hASC 的支架中表现出基质沉积和组织增加以及胶原蛋白 I 基因表达的减少。具有 20% TCP 的 3D 生物绘图 PCL 支架显示出钙沉积、内源性碱性磷酸酶活性和骨桥蛋白基因表达升高。评估了由 hASC 接种的 3D 生物标绘 PCL-TCP、电纺 PCL 和 3D 生物标绘 PCL-dECM 相组成的骨软骨支架,并证明了位点特异性骨软骨组织特征。
更新日期:2019-12-27
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