3D printing is transforming traditional processing methods for applications ranging from tissue engineering to optics. To fulfill its maximum potential, 3D printing requires a robust technique for producing structures with precise 3D (x, y, and z) control of mechanical properties. Previous efforts to realize such spatial control of modulus within 3D‐printed parts have largely focused on low‐resolution (from mm to cm scale) multimaterial processes and grayscale approaches that spatially vary the modulus in the x–y plane and energy dose‐based (E = I0 texp) models that do not account for the resin's sublinear response to irradiation intensity. Here, a novel approach for through‐thickness (z) voxelated control of mechanical properties within a single‐material, monolithic part is demonstrated. Control over the local modulus is enabled by a predictive model that incorporates the material's nonreciprocal dose response. The model is validated by application of atomic force microscopy to map the through‐thickness modulus on multilayered 3D parts. Overall, both smooth gradations (30 MPa change over ≈75 μm) and sharp step changes (30 MPa change over ≈5 μm) in the modulus are realized in poly(ethylene glycol) diacrylate‐based 3D constructs, paving the way for advancements in tissue engineering, stimuli–responsive 4D printing, and graded metamaterials.

Successful 3D scaffold designs for musculoskeletal tissue engineering necessitate full consideration of the form and function of the tissues of interest. When designing structures for engineering cartilage and osteochondral tissues, one must reconcile the need to develop a mechanically robust system that maintains the health of cells embedded in the scaffold. In this work, we present an approach that decouples the mechanical and biochemical needs and allows for the independent development of the structural and cellular niches in a scaffold. Using the highly tuned capabilities of digital light processing-based stereolithography, structures with complex architectures are achieved over a range of effective porosities and moduli. The 3D printed structure is infilled with mesenchymal stem cells and soft biomimetic hydrogels, which are specifically formulated with extracellular matrix analogs and tethered growth factors to provide selected biochemical cues for the guided differentiation towards chondrogenesis and osteogenesis. We demonstrate the ability to utilize these structures to (a) infill a focal chondral defect and mitigate macroscopic and cellular level changes in the cartilage surrounding the defect, and (b) support the development of a stratified multi-tissue scaffold for osteochondral tissue engineering.

Growth plate injuries affecting the pediatric population may cause unwanted bony repair tissue that leads to abnormal bone elongation. Clinical treatment involves bony bar resection and implantation of an interpositional material, but success is limited and the bony bar often reforms. No treatment attempts to regenerate the growth plate cartilage. Herein we develop a 3D printed growth plate mimetic composite as a potential regenerative medicine approach with the goal of preventing limb length discrepancies and inducing cartilage regeneration. A poly(ethylene glycol)-based resin was used with digital light processing to 3D print a mechanical support structure infilled with a soft cartilage-mimetic hydrogel containing chondrogenic cues. Our biomimetic composite has similar mechanical properties to native rabbit growth plate and induced chondrogenic differentiation of rabbit mesenchymal stromal cells in vitro. We evaluated its efficacy as a regenerative interpositional material applied after bony bar resection in a rabbit model of growth plate injury. Radiographic imaging was used to monitor limb length and tibial plateau angle, microcomputed tomography assessed bone morphology, and histology characterized the repair tissue that formed. Our 3D printed growth plate mimetic composite resulted in improved tibial lengthening compared to an untreated control, cartilage-mimetic hydrogel only condition, and a fat graft. However, in vivo the 3D printed growth plate mimetic composite did not show cartilage regeneration within the construct histologically. Nevertheless, this study demonstrates the feasibility of a 3D printed biomimetic composite to improve limb lengthening, a key functional outcome, supporting its further investigation as a treatment for growth plate injuries.

Agarose gels are excellent candidates for tissue engineering as they are tunable, viscoelastic, and show a pronounced strain-stiffening response. These characteristics make them ideal to create in vitro environments to...

The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adem.202101543.