Hydrogel Injections Customize Cartilage Repair

A novel bioprinting device can build three-dimensional (3D) bioscaffolds capable of regenerating deficient cartilage tissue, according to a new study.

Developed at the University of Melbourne (Melbourne, Australia), St. Vincent's Hospital (Melbourne, Australia), and other institutions, the handheld BioPen 3D additive printing device can extrude hydrogel in a core/shell manner that preserves cell viability during the biofabrication process. For the study, human adipose derived mesenchymal stem cells (hADSCs) were harvested from the infra-patellar fat pad of donor patients affected by osteoarthritis, and cultured in the presence of chondrogenic stimuli for eight weeks in vitro.

In order to prove that they can be utilized for biofabrication of human cartilage, the hADSCs were laden in gelatin methacrylate (GelMa) and hyaluronic acid methacrylate (HAMa) hydrogels, and subsequently extruded via the BioPen to generate bioscaffolds that formed hyaline-like cartilage. To control the size and shape of the BioPen scaffolds, the researchers used polydimethylsiloxane (PDMS) cylindrical molds to create a desired shape with regulated cell numbers. Immediately after extrusion, samples were irradiated with ultraviolet (UV) light for polymerization.

Capacity to produce hyaline-like neocartilage was analyzed via histology, gene, and protein expression analysis. Neocartilage formation was defined by protein localization and organization of the main components of hyaline cartilage, and a series of mechanical loading tests for compression and atomic force microscopy (AFM) were used to determine surface topology and physical properties with time. The results revealed generation of mature fibrillary collagen after eight weeks of chondrogenesis. The study was published on August 21, 2018, in Biofabrication.

“A comprehensive characterization including gene and protein expression analyses, immunohistology, confocal microscopy, second harmonic generation, light sheet imaging, atomic force mycroscopy and mechanical unconfined compression demonstrated that our strategy resulted in human hyaline-like cartilage formation,” concluded senior author Claudia Di Bella, PhD, of the University of Melbourne, and colleagues. “Our in situ biofabrication approach represents an innovation with important implications for customizing cartilage repair in patients with cartilage injuries and osteoarthritis.”

Regenerating robust articular hyaline-like cartilage is a key priority in musculoskeletal tissue engineering in order to prevent cost-intensive degenerative osteoarthritis that limits quality of life. The integration of mesenchymal stem cells and 3D printing technologies has shown significant promise in bone tissue engineering, but the key challenge remains in transferring the bench-based technology to the operating room for real-time applications.

Related Links:
University of Melbourne
St. Vincent's Hospital