Sonthithai Pacharapan, Kaewkong Pakkanun, Channasanon Somruethai, Tanodekaew Siriporn
National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Phahonyothin Road, Klong Nueng, Klong Luang, Pathum Thani 12120, Thailand.
ACS Biomater Sci Eng. 2025 Apr 14;11(4):2157-2166. doi: 10.1021/acsbiomaterials.4c02409. Epub 2025 Mar 19.
The advancement of 3D printing technology offers a sophisticated solution for tissue engineering and regenerative medicine. Several printable hydrogels have been developed with specific designs for certain tissues. However, there are few effective 3D-printed hydrogels for cartilage tissue engineering due to challenges with the hydrogel printability and the redifferentiation capacity of the articular chondrocytes on the hydrogel. This research study combined a PEG-PLA copolymer with gelatin to develop 3D-printed scaffolds for cartilage regeneration. Different hydrogel samples were prepared and studied regarding the effects of PLA chain length, gelatin content, and cross-linker concentration on the mechanical properties, swelling ability, and degradability of the hydrogels. An increase in the swelling ratio was observed, resulting in diminished compressive properties and accelerated degradation of the hydrogels with increased gelatin or decreased cross-linker and PLA chain length. Porcine articular chondrocytes were seeded onto the hydrogel scaffolds to assess cell adhesion, proliferation, and redifferentiation capability. Hydrogels with high swelling ability promoted the initial adhesion of cells on the scaffold, hence significantly increasing chondrocyte proliferation within 2 weeks of culture. Lowering the compressive modulus by increasing gelatin content improved chondrogenic redifferentiation. Glycosaminoglycan secretion was significantly enhanced when cells grew on hydrogels with greater amounts of gelatin. Furthermore, immunofluorescence staining of the cell-loaded hydrogels showed clusters of cells with a dense accumulation of a type II collagen network, a basis component of the cartilaginous matrix. Neither the PLA chain length nor the cross-linker amount affected chondrogenic function. The present study demonstrates that the PEG-PLA/gelatin hydrogels with increasing amounts of gelatin provide an optimal combination of swelling ratio, compressive modulus, and degradation rate, resulting in an appropriate environment to support the growth and redifferentiation of articular chondrocytes. This 3D-printed PEG-PLA/gelatin hydrogel will be useful for cartilage tissue engineering and possibly contribute to a new approach for cartilage defect treatment.
3D打印技术的进步为组织工程和再生医学提供了一种精密的解决方案。已经开发出几种具有特定设计的可打印水凝胶用于某些组织。然而，由于水凝胶的可打印性以及关节软骨细胞在水凝胶上的再分化能力方面存在挑战，用于软骨组织工程的有效3D打印水凝胶很少。本研究将聚乙二醇-聚乳酸（PEG-PLA）共聚物与明胶结合，以开发用于软骨再生的3D打印支架。制备了不同的水凝胶样品，并研究了聚乳酸链长度、明胶含量和交联剂浓度对水凝胶的机械性能、溶胀能力和降解性的影响。观察到溶胀率增加，随着明胶含量增加、交联剂和聚乳酸链长度减少，水凝胶的压缩性能降低且降解加速。将猪关节软骨细胞接种到水凝胶支架上，以评估细胞粘附、增殖和再分化能力。具有高溶胀能力的水凝胶促进细胞在支架上的初始粘附，因此在培养2周内显著增加软骨细胞增殖。通过增加明胶含量降低压缩模量可改善软骨形成再分化。当细胞在含有更多明胶的水凝胶上生长时，糖胺聚糖分泌显著增强。此外，对负载细胞的水凝胶进行免疫荧光染色显示细胞簇，其中有密集堆积的II型胶原网络，这是软骨基质的基本成分。聚乳酸链长度和交联剂用量均不影响软骨形成功能。本研究表明，随着明胶含量增加的PEG-PLA/明胶水凝胶提供了溶胀率、压缩模量和降解速率的最佳组合，从而形成了支持关节软骨细胞生长和再分化的适宜环境。这种3D打印的PEG-PLA/明胶水凝胶将有助于软骨组织工程，并可能为软骨缺损治疗提供一种新方法。
