Department of Biomechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), 16419, Suwon, Republic of Korea.
Department of Otolaryngology, Chonnam National University Medical School, Gwangju 61186, Republic of Korea.
Theranostics. 2022 May 13;12(9):4051-4066. doi: 10.7150/thno.73146. eCollection 2022.
Bioengineering scaffolds have been improved to achieve efficient regeneration of various damaged tissues. In this study, we attempted to fabricate mechanically and biologically activated 3D printed scaffold in which porous gelatin/hydroxyapatite (G/H) as a matrix material provided outstanding mechanical properties with recoverable behavior, and human placental extracts (hPE) embedded in the scaffold were used as bioactive components. Various cell types (human adipose-derived stem cells; hASCs, pre-osteoblast; MC3T3-E1, human endothelial cell line; EA.hy926, and human dermal fibroblast; hDFs) were used to assess the effect of the hPE on cellular responses. High weight fraction (~ 70 wt%) of hydroxyapatite (HA) in a gelatin solution supplemented with glycerol was used for the G/H scaffold fabrication, and the scaffolds were immersed in hPE for the embedding (G/H/hPE scaffold). The osteogenic abilities of the scaffolds were investigated in cultured cells (hASCs) assaying for ALP activity and expression of osteogenic genes. For the test, the G/H and G/H/hPE scaffolds were implanted in the rat mastoid obliteration model. The G/H/hPE scaffold presented unique elastic recoverable properties, which are important for efficient usage of implantable scaffolds. The effects of G/H and G/H/hPE scaffold on various cell-activities including non-toxicity, biocompatibility, and cell proliferation were investigated. The results indicated that proliferation (G/H = 351.1 ± 13.3%, G/H/hPE = 430.9 ± 8.7% at day 14) and expression of osteogenic markers (: 3.4-fold, : 3.9-fold, : 1.7-fold, : 2.4-fold, and : 4.8-fold at day 21) of hASCs grown in the G/H/hPE scaffold were significantly enhanced compared with that in cells grown in the G/H scaffold. In addition, bone formation was also observed in an model using rat mastoid obliteration. and results suggested that the G/H/hPE scaffold is a potential candidate for use in bone tissue engineering.
生物工程支架已经得到改进，以实现各种受损组织的有效再生。在这项研究中，我们试图制造机械和生物激活的 3D 打印支架，其中多孔明胶/羟基磷灰石（G/H）作为基质材料提供了出色的机械性能和可恢复的特性，并且支架中嵌入的人胎盘提取物（hPE）用作生物活性成分。各种细胞类型（人脂肪来源的干细胞；hASCs、前成骨细胞；MC3T3-E1、人内皮细胞系；EA.hy926 和人真皮成纤维细胞；hDFs）用于评估 hPE 对细胞反应的影响。在补充甘油的明胶溶液中使用高重量分数（~70wt%）的羟基磷灰石（HA）来制造 G/H 支架，并将支架浸入 hPE 中进行嵌入（G/H/hPE 支架）。在培养细胞（hASCs）中测定碱性磷酸酶（ALP）活性和成骨基因表达，研究支架的成骨能力。为了进行测试，将 G/H 和 G/H/hPE 支架植入大鼠乳突闭塞模型中。G/H/hPE 支架具有独特的弹性可恢复特性，这对于有效使用植入式支架非常重要。研究了 G/H 和 G/H/hPE 支架对各种细胞活性的影响，包括细胞毒性、生物相容性和细胞增殖。结果表明，在 G/H/hPE 支架中培养的细胞增殖（G/H=351.1±13.3%，G/H/hPE=430.9±8.7%，第 14 天）和成骨标志物的表达（:3.4 倍，:3.9 倍，:1.7 倍，:2.4 倍，:4.8 倍，第 21 天）明显高于在 G/H 支架中培养的细胞。此外，在使用大鼠乳突闭塞的模型中也观察到了骨形成。和结果表明，G/H/hPE 支架是骨组织工程的潜在候选材料。
