Adaptive and context-aware volumetric printing.

We introduce Generative, Adaptive, Context-Aware 3D Printing (GRACE), a new approach combining 3D imaging, computer vision and parametric modelling to create tailored, context-aware geometries using volumetric additive manufacturing. GRACE rapidly and automatically generates complex structures capable of conforming directly around features ranging from cellular to macroscopic scales with minimal user intervention. Here we demonstrate its versatility in applications ranging from synthetic objects to biofabrication, including adaptive vascular-like geometries around cell-laden bioinks, resulting in improved functionality.

Unraveling devitalization: its impact on immune response and ectopic bone remodeling from autologous and allogeneic callus mimics.

Endochondral bone regeneration is a promising approach in regenerative medicine. Callus mimics (CMs) are engineered and remodeled into bone tissue upon implantation. The long-term objective is to fabricate a sustainable off-the-shelf treatment option for patients.

Harnessing Macromolecular Chemistry to Design Hydrogel Micro- and Macro-Environments.

Cell encapsulation within three-dimensional hydrogels is a promising approach to mimic tissues. However, true biomimicry of the intricate microenvironment, biophysical and biochemical gradients, and the macroscale hierarchical spatial organizations of native tissues is an unmet challenge within tissue engineering. This review provides an overview of the macromolecular chemistries that have been applied toward the design of cell-friendly hydrogels, as well as their application toward controlling biophysical and biochemical bulk and gradient properties of the microenvironment.

Pristine gelatin incorporation as a strategy to enhance the biofunctionality of poly(vinyl alcohol)-based hydrogels for tissue engineering applications.

Synthetic polymers, such as poly(vinyl alcohol) (PVA), are popular biomaterials for the fabrication of hydrogels for tissue engineering and regenerative medicine (TERM) applications, as they provide excellent control over the physico-chemical properties of the hydrogel. However, their bioinert nature is known to limit cell-biomaterial interactions by hindering cell infiltration, blood vessel recruitment and potentially limiting their integration with the host tissue. Efforts in the field have therefore focused on increasing the biofunctionality of synthetic hydrogels, without limiting the advantages associated with their tailorability and controlled release capacity.

Spatial-Selective Volumetric 4D Printing and Single-Photon Grafting of Biomolecules within Centimeter-Scale Hydrogels via Tomographic Manufacturing.

Conventional additive manufacturing and biofabrication techniques are unable to edit the chemicophysical properties of the printed object postprinting. Herein, a new approach is presented, leveraging light-based volumetric printing as a tool to spatially pattern any biomolecule of interest in custom-designed geometries even across large, centimeter-scale hydrogels. As biomaterial platform, a gelatin norbornene resin is developed with tunable mechanical properties suitable for tissue engineering applications.

Clinical Applicability of Visible Light-Mediated Cross-linking for Structural Soft Tissue Reconstruction.

Visible light-mediated cross-linking has utility for enhancing the structural capacity and shape fidelity of laboratory-based polymers. With increased light penetration and cross-linking speed, there is opportunity to extend future applications into clinical spheres. This study evaluated the utility of a ruthenium/sodium persulfate photocross-linking system for increasing structural control in heterogeneous living tissues as an example, focusing on unmodified patient-derived lipoaspirate for soft tissue reconstruction.

Osteoinductive calcium phosphate with submicron topography as bone graft substitute for maxillary sinus floor augmentation: A translational study.

Objectives: The aim of this study was the preclinical and clinical evaluation of osteoinductive calcium phosphate with submicron surface topography as a bone graft substitute for maxillary sinus floor augmentation (MSFA).

Material And Methods: A preclinical sheep model of MSFA was used to compare a calcium phosphate with submicron needle-shaped topography (BCP , MagnetOs Granules, Kuros Biosciences BV) to a calcium phosphate with submicron grain-shaped topography (BCP ) and autologous bone graft (ABG) as controls. Secondly, a 10-patient, prospective, randomized, controlled trial was performed to compare BCP to ABG in MSFA with two-stage implant placement.

Acceleration of Bone Regeneration Induced by a Soft-Callus Mimetic Material.

Clinical implementation of endochondral bone regeneration (EBR) would benefit from the engineering of devitalized cartilaginous constructs of allogeneic origins. Nevertheless, development of effective devitalization strategies that preserves extracellular matrix (ECM) is still challenging. The aim of this study is to investigate EBR induced by devitalized, soft callus-mimetic spheroids.

Development and Characterization of Gelatin-Norbornene Bioink to Understand the Interplay between Physical Architecture and Micro-Capillary Formation in Biofabricated Vascularized Constructs.

The principle challenge for engineering viable, cell-laden hydrogel constructs of clinically-relevant size, is rapid vascularization, in order to moderate the finite capacity of passive nutrient diffusion. A multiscale vascular approach, with large open channels and bulk microcapillaries may be an admissible approach to accelerate this process, promoting overall pre-vascularization for long-term viability of constructs. However, the limited availability of bioinks that possess suitable characteristics that support both fabrication of complex architectures and formation of microcapillaries, remains a barrier to advancement in this space.

Strategies for inclusion of growth factors into 3D printed bone grafts.

There remains a critical need to develop new technologies and materials that can meet the demands of treating large bone defects. The advancement of 3-dimensional (3D) printing technologies has allowed the creation of personalized and customized bone grafts, with specific control in both macro- and micro-architecture, and desired mechanical properties. Nevertheless, the biomaterials used for the production of these bone grafts often possess poor biological properties.

Endochondral Bone Regeneration by Non-autologous Mesenchymal Stem Cells.

Mimicking endochondral bone formation is a promising strategy for bone regeneration. To become a successful therapy, the cell source is a crucial translational aspect. Typically, autologous cells are used.

Contrast enhanced computed tomography for real-time quantification of glycosaminoglycans in cartilage tissue engineered constructs.

Tissue engineering and regenerative medicine are two therapeutic strategies to treat, and to potentially cure, diseases affecting cartilaginous tissues, such as osteoarthritis and cartilage defects. Insights into the processes occurring during regeneration are essential to steer and inform development of the envisaged regenerative strategy, however tools are needed for longitudinal and quantitative monitoring of cartilage matrix components. In this study, we introduce a contrast-enhanced computed tomography (CECT)-based method using a cationic iodinated contrast agent (CA4+) for longitudinal quantification of glycosaminoglycans (GAG) in cartilage-engineered constructs.

Soft-molecular imprinted electrospun scaffolds to mimic specific biological tissues.

The fabrication of bioactive scaffolds able to mimic the in vivo cellular microenvironment is a challenge for regenerative medicine. The creation of sites for the selective binding of specific endogenous proteins represents an attractive strategy to fabricate scaffolds able to elicit specific cell response. Here, electrospinning (ESP) and soft-molecular imprinting (soft-MI) techniques were combined to fabricate a soft-molecular imprinted electrospun bioactive scaffold (SMIES) for tissue regeneration.

Toward mimicking the bone structure: design of novel hierarchical scaffolds with a tailored radial porosity gradient.

Guiding bone regeneration poses still unmet challenges due to several drawbacks of current standard treatments in the clinics. A possible solution may rely on the use of three-dimensional scaffolds with optimized structural properties in combination with human mesenchymal stem cells (hMSCs). Bone presents a radial gradient structure from the outside, where the cortical bone is more compact (porosity ranging from 5% to 10%), toward the inner part, where the cancellous bone is more porous (porosity ranging from 50% to 90%).

Additive manufactured polymeric 3D scaffolds with tailored surface topography influence mesenchymal stromal cells activity.

Additive manufactured three-dimensional (3D) scaffolds with tailored surface topography constitute a clear advantage in tissue regeneration strategies to steer cell behavior. 3D fibrous scaffolds of poly(ethylene oxide terephthalate)/poly(butylene terephthalate) block copolymer presenting different fiber surface features were successfully fabricated by additive manufacturing combined with wet-spinning, in a single step, without any post-processing. The optimization of the processing parameters, mainly driven by different solvent/non-solvent combinations, led to four distinct scaffold types, with average surface roughness values ranging from 0.

Surface energy and stiffness discrete gradients in additive manufactured scaffolds for osteochondral regeneration.

Swift progress in biofabrication technologies has enabled unprecedented advances in the application of developmental biology design criteria in three-dimensional scaffolds for regenerative medicine. Considering that tissues and organs in the human body develop following specific physico-chemical gradients, in this study, we hypothesized that additive manufacturing (AM) technologies would significantly aid in the construction of 3D scaffolds encompassing such gradients. Specifically, we considered surface energy and stiffness gradients and analyzed their effect on adult bone marrow derived mesenchymal stem cell differentiation into skeletal lineages.