Core–shell bioprinting as a strategy to apply differentiation factors in a spatially defined manner inside osteochondral tissue substitutes

Abstract

One of the key challenges in osteochondral tissue engineering is to define specified zones with varying material properties, cell types and biochemical factors supporting locally adjusted differentiation into the osteogenic and chondrogenic lineage, respectively. Herein, extrusion-based core-shell bioprinting is introduced as a potent tool allowing a spatially defined delivery of cell types and differentiation factors TGF-β3 and BMP-2 in separated compartments of hydrogel strands, and, therefore, a local supply of matching factors for chondrocytes and osteoblasts. Ink development was based on blends of alginate and methylcellulose, in combination with varying concentrations of the nanoclay Laponite whose high affinity binding capacity for various molecules was exploited. Release kinetics of model molecules was successfully tuned by Laponite addition. Core-shell bioprinting was proven to generate well-oriented compartments within one strand as monitored by optical coherence tomography in a non-invasive manner. Chondrocytes and osteoblasts were applied each in the shell while the respective differentiation factors (TGF-β3, BMP-2) were provided by a Laponite-supported core serving as central factor depot within the strand, allowing directed differentiation of cells in close contact to the core. Experiments with bi-zonal constructs, comprising an osteogenic and a chondrogenic zone, revealed that the local delivery of the factors from the core reduces effects of these factors on the cells in the other scaffold zone. These observations prove the general suitability of the suggested system for co-differentiation of different cell types within a zonal construct.

Treatment of Critical Size Femoral Bone Defects with Biomimetic Hybrid Scaffolds of 3D Plotted Calcium Phosphate Cement and Mineralized Collagen Matrix

“…Thus, cells may grow only on the outer surface [ 10 ]. Creative 3D bioprinting can solve these problems of oxygen and nutrient supply and also allows functionalization of the scaffolds [ 27 , 28 ]. The ideal scaffold can temporarily replace natural tissues, interact with the surrounding microenvironment, and actively guide cellular events, ultimately leading to faster bone formation [ 4 ].…”

Biofabrication of the osteochondral unit and its applications: Current and future directions for 3D bioprinting

“…Kilian et al 92 Extrusion-based hBMSCs Methacrylated hyaluronic acid (MeHA)/ PCL; incorporating kartogening and beta-TCP They manufactured a triphasic construct for osteochondral defect regeneration. The subchondral bone layer was made of PCL and beta-TCP; the cartilage section had MeHA with hBMSCs, PCL with kartogenin; a top anti-inflammatory layer was made of MeHA with diclofenac solution.…”

Bioinks for Space Missions: The Influence of Long‐Term Storage of Alginate‐Methylcellulose‐Based Bioinks on Printability as well as Cell Viability and Function

“…[11] During alginate crosslinking and the subsequent cultivation, the methylcellulose is partially released, forming a crosslinked construct of mainly alginate.. [11,12] This versatile ink has been successfully applied for bioprinting of various mammalian cell types such as pancreatic islets of Langerhans and chondrocytes, but also for bioprinting of microalgae. [13][14][15][16][17][18][19] Based on the promising results in these ground-based studies, Alg-MC was the first bioink to be selected by the company OHB for use in space. As part of the ISS mission Cosmic Kiss of the German ESA astronaut Matthias Maurer, it was used as one of two for the mission selected bioinks to generate constructs with the aid of a hand-held printer, which in combination with dermal fibroblasts should later provide rapid assistance in the wound closure of large-area skin injuries.…”

“…[ 11 ] During alginate crosslinking and the subsequent cultivation, the methylcellulose is partially released, forming a crosslinked construct of mainly alginate.. [ 11,12 ] This versatile ink has been successfully applied for bioprinting of various mammalian cell types such as pancreatic islets of Langerhans and chondrocytes, but also for bioprinting of microalgae. [ 13–19 ]…”