Direct 3D Printing of High Strength Biohybrid Gradient Hydrogel Scaffolds for Efficient Repair of Osteochondral Defect

Abstract

The emerging 3D printing technique allows for tailoring hydrogel‐based soft structure tissue scaffolds for individualized therapy of osteochondral defects. However, the weak mechanical strength and uncontrollable swelling intrinsic to conventional hydrogels restrain their use as bioinks. Here, a high‐strength thermoresponsive supramolecular copolymer hydrogel is synthesized by one‐step copolymerization of dual hydrogen bonding monomers, N‐acryloyl glycinamide, and N‐[tris(hydroxymethyl)methyl] acrylamide. The obtained copolymer hydrogels demonstrate excellent mechanical properties—robust tensile strength (up to 0.41 MPa), large stretchability (up to 860%), and high compressive strength (up to 8.4 MPa). The rapid thermoreversible gel ⇔ sol transition behavior makes this copolymer hydrogel suitable for direct 3D printing. Successful preparation of 3D‐printed biohybrid gradient hydrogel scaffolds is demonstrated with controllable 3D architecture, owing to shear thinning property which allows continuous extrusion through a needle and also immediate gelation of fluid upon deposition on the cooled substrate. Furthermore, this biohybrid gradient hydrogel scaffold printed with transforming growth factor beta 1 and β‐tricalciumphosphate on distinct layers facilitates the attachment, spreading, and chondrogenic and osteogenic differentiation of human bone marrow stem cells (hBMSCs) in vitro. The in vivo experiments reveal that the 3D‐printed biohybrid gradient hydrogel scaffolds significantly accelerate simultaneous regeneration of cartilage and subchondral bone in a rat model.

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

“…For tendon/ligament-bone interface, scaffold design has long relied on the creation of stratified layers with or without minerals and reconstructed graft materials for interface repair [8]; however, this does not truly recreate the physiological structure. Therefore, multiphasic and gradient fiber-based scaffold designs, along with strategic patterning of key biochemical cues, such as growth factors, have emerged to emulate multitissue architecture [9,10] while controlling stem cell distribution and differentiation both in vitro and in vivo [11,12]. Comparably, biomaterials-based strategies for osteochondral defects have relied on the use of multilayered polymeric scaffolds, which are designed to generate structural templates to mimic the cartilaginous layer, the calcified cartilage, and subchondral bone, and metallic scaffolds with architectural and biochemical gradients [13,14].…”

“…Nanofibrous scaffolds have been widely used for tendon-tobone regeneration as these biomaterials act as a physical platform mimicking 3D fibrous collagenous hierarchical structure [29,30]. In contrast, 3D printing and hydrogels have been used for mimicking physical properties of the osteochondral unit, as this combination demonstrates good physical and mechanical performance [12,31].…”

3D Printing of Multifunctional Hydrogels

“…Owing to their high elasticity and softness, biocompatibility, and multifunctionality, [1] hydrogels have been applied in various fields, such as bioengineering, [2][3][4] smart devices, [5][6][7][8] soft robotics, [9][10][11] and agriculture. [13][14][15][16][17][18][19][20][21][22] 3D printing technology, which does not require molds, dies, or masks, allows turning During printing, the applied shear stress in the printhead must exceed the yield stress τ y for the inks to flow through the nozzle. Therefore, the development of patterning hydrogels from microscale to macroscale is critical for applications and has attracted a lot of research efforts.…”

Preparation and properties of dopamine‐modified alginate/chitosan–hydroxyapatite scaffolds with gradient structure for bone tissue engineering

“…Although the reason why the gradient scaffold had better osteogenic activity than the homogeneous scaffold was unclear now, we believe that the gradient pore size might be easy for bone cell fibrous to penetrate and promote the biological tissue to work well, as other researches reported. 47…”