Hacettepe University, Bioengineering Department, 06800 Beytepe, Ankara, Turkey; Hacettepe University, Chemical Engineering Department, 06800 Beytepe, Ankara, Turkey.
Hacettepe University, Bioengineering Department, 06800 Beytepe, Ankara, Turkey; Hacettepe University, Chemical Engineering Department, 06800 Beytepe, Ankara, Turkey.
Mater Sci Eng C Mater Biol Appl. 2021 Jun;125:112092. doi: 10.1016/j.msec.2021.112092. Epub 2021 Apr 1.
In osteochondral tissue engineering, while the biochemical and mechanical properties of hydrogels guide stem cell proliferation and differentiation, physical and chemical stimulators also affect the differentiation of stem cells. Herein, we presented a patient and tissue-specific strategy for the development of biomimetic osteochondral constructs with gradient compositions. Osteochondral constructs were fabricated by gradually printing of bio-inks consisting of therapeutic platelet-rich plasma (PRP), adipose tissue-derived mesenchymal stem cells (AdMSCs), and extracellular matrix (ECM) mimetic hydrogel, microwave-assisted methacrylated gelatin (Gel-MA). Periodic application of light in the near infrared region (600-1200 nm wavelength) was used to induce platelet activation and also AdMSCs' differentiation. Gel-MA has the same structure as type I collagen and PRP has cartilage tissue-specific bioactive components, so they provide the appropriate environment for the differentiation of AdMSCs to osteochondral tissue. Histology, immunocytochemistry, and biochemical analyses indicated enhanced glycosaminoglycan (GAG) and calcium content, mineralization, and ECM production. Furthermore, RT-PCR results indicated the expressions of bone- and cartilage-specific genes. In conclusion, the periodically photoactivated hydrogels with relatively low degradation rate and high mechanical strength, and tissue-specific biomimetic structure promoted in-vitro osteochondral tissue formation including hyaline and hypertrophic cartilage and bone phases.
在骨软骨组织工程中，水凝胶的生化和机械性能指导干细胞的增殖和分化，而物理和化学刺激物也影响干细胞的分化。在此，我们提出了一种针对具有梯度组成的仿生骨软骨构建体的患者和组织特异性开发策略。通过逐渐打印由治疗性富含血小板血浆 (PRP)、脂肪组织来源的间充质干细胞 (AdMSCs) 和细胞外基质 (ECM) 仿生水凝胶、微波辅助甲基丙烯酰化明胶 (Gel-MA) 组成的生物墨水来制造骨软骨构建体。周期性应用近红外区域（600-1200nm 波长）的光用于诱导血小板活化和 AdMSCs 的分化。Gel-MA 的结构与 I 型胶原相同，PRP 具有软骨组织特异性生物活性成分，因此它们为 AdMSCs 向骨软骨组织的分化提供了合适的环境。组织学、免疫细胞化学和生化分析表明糖胺聚糖 (GAG) 和钙含量、矿化和 ECM 产生增加。此外，RT-PCR 结果表明骨和软骨特异性基因的表达。总之，具有相对较低降解率和较高机械强度的周期性光激活水凝胶和组织特异性仿生结构促进了包括透明软骨和肥大软骨以及骨相在内的体外骨软骨组织形成。
