Naolou Toufik, Schadzek Nadine, Hornbostel Jan Mathis, Pepelanova Iliyana, Frommer Miriam, Lötz Franziska, Sauheitl Leopold, Dultz Stefan, Felde Vincent J M N L, Myklebost Ola, Lee-Thedieck Cornelia
Institute of Cell Biology and Biophysics, Department of Cell Biology, Leibniz University Hannover, Herrenhaeuser Strasse 2, 30419 Hannover, Germany.
Institute of Technical Chemistry, Leibniz University Hannover, Callinstrasse 5, 30167 Hannover, Germany.
Biofabrication. 2025 Mar 27;17(2). doi: 10.1088/1758-5090/adbb90.
Patients suffering from large bone defects are in urgent need of suitable bone replacements. Besides biocompatibility, such replacements need to mimic the 3D architecture of bone and match chemical, mechanical and biological properties, ideally promoting ossification. As natural bone mainly contains collagen type I and carbonate hydroxyapatite, a 3D-printable biomaterial consisting of methacrylated gelatin (GelMA) and nanohydroxyapatite (nHAp) would be beneficial to mimic the composition and shape of natural bone. So far, such nanocomposite hydrogels (NCH) suffered from unsatisfactory rheological properties making them unsuitable for extrusion-based 3D printing with high structural fidelity. In this study, we introduce a novel GelMA/nHAp NCH composition, incorporating the rheological modifier carbomer to improve rheological properties and addressing the challenge of calcium cations released from nHAp that hinder GelMA gelation. Leveraging its shear-thinning and self-healing properties, the NCH ink retains its shape and forms cohesive structures after deposition, which can be permanently stabilized by subsequent UV crosslinking. Consequently, the NCH enables the printing of 3D structures with high shape fidelity in all dimensions, including the-direction, allowing the fabrication of highly macroporous constructs. Both the uncured and the UV crosslinked NCH behave like a viscoelastic solid, with'>″ at deformations up to 100-200 %. After UV crosslinking, the NCH can, depending on the GelMA concentration, reach storage moduli of approximately 10 to over 100 kPa and a mean Young's Modulus of about 70 kPa. The printed scaffolds permit not only cell survival but also osteogenic differentiation, highlighting their potential for bone tissue engineering.
患有大骨缺损的患者迫切需要合适的骨替代物。除了生物相容性外，这种替代物还需要模仿骨骼的三维结构，并匹配化学、机械和生物学特性，理想情况下促进骨化。由于天然骨主要包含I型胶原蛋白和碳酸羟基磷灰石，一种由甲基丙烯酸化明胶（GelMA）和纳米羟基磷灰石（nHAp）组成的可3D打印生物材料将有助于模仿天然骨的组成和形状。到目前为止，这种纳米复合水凝胶（NCH）的流变性能不尽人意，使其不适用于具有高结构保真度的基于挤出的3D打印。在本研究中，我们引入了一种新型的GelMA/nHAp NCH组合物，加入流变改性剂卡波姆以改善流变性能，并解决从nHAp释放的钙阳离子阻碍GelMA凝胶化的挑战。利用其剪切变稀和自愈特性，NCH墨水在沉积后保持其形状并形成粘性结构，随后通过紫外线交联可使其永久稳定。因此，NCH能够在所有维度上以高形状保真度打印3D结构，包括z方向，从而能够制造高度大孔的构建体。未固化和紫外线交联的NCH在高达100 - 200% 的变形下均表现出粘弹性固体的特性，'>″ 。紫外线交联后，根据GelMA浓度，NCH的储能模量可达到约10至超过100 kPa，平均杨氏模量约为70 kPa。打印的支架不仅允许细胞存活，还能促进成骨分化，突出了它们在骨组织工程中的潜力。
