Aligned Gelatin Microribbon Scaffolds with Hydroxyapatite Gradient for Engineering the Bone–Tendon Interface

• Published in: Tissue engineering. Part A 2022-08, Vol.28 (15-16), p.712-723
• Main Authors: Stanton, Alice E, Tong, Xinming, Jing, Serena L, Behn, Anthony, Storaci, Hunter, Yang, Fan
• Format: Article
• Language: English
• Subjects: Anterior cruciate ligament; Bone biomaterials; Cartilage; Cell culture; Cell Differentiation; Durapatite - pharmacology; Engineering; Gelatin; Gelatin - pharmacology; Humans; Hydrogels; Hydrogels - pharmacology; Hydroxyapatite; Injuries; Mesenchymal stem cells; Mesenchyme; Mimicry; Nanoparticles; Original; Original Articles; Osteogenesis; Phenotypes; Stem cells; Tendons; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2021.0099

Injuries of the bone-to-tendon interface, such as rotator cuff and anterior cruciate ligament tears, are prevalent musculoskeletal injuries, yet effective methods for repair remain elusive. Tissue engineering approaches that use cells and biomaterials offer a promising potential solution for engineering the bone–tendon interface, but previous strategies require seeding multiple cell types and use of multiphasic scaffolds to achieve zonal-specific tissue phenotype. Furthermore, mimicking the aligned tissue morphology present in native bone–tendon interface in three-dimensional (3D) remains challenging. To facilitate clinical translation, engineering bone–tendon interface using a single cell source and one continuous scaffold with alignment cues would be more attractive but has not been achieved before. To address these unmet needs, in this study, we develop an aligned gelatin microribbon (μRB) hydrogel scaffold with hydroxyapatite nanoparticle (HA-np) gradient for guiding zonal-specific differentiation of human mesenchymal stem cell (hMSC) to mimic the bone–tendon interface. We demonstrate that aligned μRBs led to cell alignment in 3D, and HA gradient induced zonal-specific differentiation of mesenchymal stem cells that resemble the transition at the bone–tendon interface. Short chondrogenic priming before exposure to osteogenic factors further enhanced the mimicry of bone–cartilage–tendon transition with significantly improved tensile moduli of the resulting tissues. In summary, aligned gelatin μRBs with HA gradient coupled with optimized soluble factors may offer a promising strategy for engineering bone–tendon interface using a single cell source.