Preclinical Safety of a 3D-Printed Hydroxyapatite-Demineralized Bone Matrix Scaffold for Spinal Fusion.

Study Design: Prospective, randomized, controlled preclinical study.

Objective: The objective of this study was to compare the host inflammatory response of our previously described hyperelastic, 3D-printed (3DP) hydroxyapatite (HA)-demineralized bone matrix (DBM) composite scaffold to the response elicited with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a preclinical rat posterolateral lumbar fusion model.

Summary Of Background Data: Our group previously found that this 3D-printed HA-DBM composite material shows promise as a bone graft substitute in a preclinical rodent model, but its safety profile had yet to be assessed.

Regional gene therapy for bone healing using a 3D printed scaffold in a rat femoral defect model.

At the present time there are no consistently satisfactory treatment options for some challenging bone loss scenarios. We have previously reported on the properties of a novel 3D-printed hydroxyapatite-composite material in a pilot study, which demonstrated osteoconductive properties but was not tested in a rigorous, clinically relevant model. We therefore utilized a rat critical-sized femoral defect model with a scaffold designed to match the dimensions of the bone defect.

Osteoinductivity and biomechanical assessment of a 3D printed demineralized bone matrix-ceramic composite in a rat spine fusion model.

We recently developed a recombinant growth factor-free bone regenerative scaffold composed of stoichiometric hydroxyapatite (HA) ceramic particles and human demineralized bone matrix (DBM) particles (HA-DBM). Here, we performed the first pre-clinical comparative evaluation of HA-DBM relative to the industry standard and established positive control, recombinant human bone morphogenetic protein-2 (rhBMP-2), using a rat posterolateral spinal fusion model (PLF). Female Sprague-Dawley rats underwent bilateral L4-L5 PLF with implantation of the HA-DBM scaffold or rhBMP-2.

Building Organs Using Tissue-Specific Microenvironments: Perspectives from a Bioprosthetic Ovary.

Recent research in tissue engineering and regenerative medicine has elucidated the importance of the matrisome. The matrisome, effectively the skeleton of an organ, provides physical and biochemical cues that drive important processes such as differentiation, proliferation, migration, and cellular morphology. Leveraging the matrisome to control these and other tissue-specific processes will be key to developing transplantable bioprosthetics.

Inclusion of a 3D-printed Hyperelastic Bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold.

Regenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized collagen scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regeneration in vivo. Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized collagen scaffold to improve mechanical and biological activity.

Influence of Geometry and Architecture on the Success of 3D-Printed Scaffolds for Spinal Fusion.

We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed material comprising hydroxyapatite (HA) and demineralized bone matrix (DBM) for bone regeneration. This material has demonstrated the capacity to promote re-mineralization of the DBM particles within the scaffold struts and shows potential to promote successful spine fusion. Here, we investigate the role of geometry and architecture in osteointegration, vascularization, and facilitation of spine fusion in a preclinical model.

3D extruded composite thermoelectric threads for flexible energy harvesting.

Whereas the rigid nature of standard thermoelectrics limits their use, flexible thermoelectric platforms can find much broader applications, for example, in low-power, wearable energy harvesting for internet-of-things applications. Here we realize continuous, flexible thermoelectric threads via a rapid extrusion of 3D-printable composite inks (BiTe n- or p-type micrograins within a non-conducting polymer as a binder) followed by compression through a roller-pair, and we demonstrate their applications in flexible, low-power energy harvesting. The thermoelectric power factors of these threads are enhanced up to 7 orders-of-magnitude after lateral compression, principally due to improved conductivity resulting from reduced void volume fraction and partial alignment of thermoelectric micrograins.

3D-Printed Ceramic-Demineralized Bone Matrix Hyperelastic Bone Composite Scaffolds for Spinal Fusion.

Although numerous spinal biologics are commercially available, a cost-effective and safe bone graft substitute material for spine fusion has yet to be proven. In this study, "3D-Paints" containing varying volumetric ratios of hydroxyapatite (HA) and human demineralized bone matrix (DBM) in a poly(lactide-co-glycolide) elastomer were three-dimensional (3D) printed into scaffolds to promote osteointegration in rats, with an end goal of spine fusion without the need for recombinant growth factor. Spine fusion was evaluated by manual palpation, and osteointegration and bone formation within scaffold struts were evaluated by laboratory and synchrotron microcomputed tomography and histology.

Three-Dimensionally Printed Hyperelastic Bone Scaffolds Accelerate Bone Regeneration in Critical-Size Calvarial Bone Defects.

Background: Autologous bone grafts remain the gold standard for craniofacial reconstruction despite limitations of donor-site availability and morbidity. A myriad of commercial bone substitutes and allografts are available, yet no product has gained widespread use because of inferior clinical outcomes. The ideal bone substitute is both osteoconductive and osteoinductive.

Nanopatterning and Bioprinting in Orthopedic Surgery.

In part 1 of this article, the authors explore nanoscale modifications of the surfaces of biomaterials, which offer an exciting potential venue for the prevention of bacterial adhesion and growth. Despite advances in the design and manufacture of implants, infection remains an important and often devastating mode of failure. In part 2, additive technologies for tissue engineering, live cell printing (bioprinting), and tissue fabrication are briefly introduced.

Voltaglue Bioadhesives Energized with Interdigitated 3D-Graphene Electrodes.

Soft tissue fixation of implant and bioelectrodes relies on mechanical means (e.g., sutures, staples, and screws), with associated complications of tissue perforation, scarring, and interfacial stress concentrations.

Vascularization of Natural and Synthetic Bone Scaffolds.

Vascularization of engineered bone tissue is critical for ensuring its survival after implantation. In vitro pre-vascularization of bone grafts with endothelial cells is a promising strategy to improve implant survival. In this study, we pre-cultured human smooth muscle cells (hSMCs) on bone scaffolds for 3 weeks followed by seeding of human umbilical vein endothelial cells (HUVECs), which produced a desirable environment for microvasculature formation.

NiTi-Nb micro-trusses fabricated via extrusion-based 3D-printing of powders and transient-liquid-phase sintering.

Unlabelled: We present a novel additive manufacturing method for NiTi-Nb micro-trusses combining (i) extrusion-based 3D-printing of liquid inks containing NiTi and Nb powders, solvents, and a polymer binder into micro-trusses with 0/90° ABAB layers of parallel, ∼600 µm struts spaced 1 mm apart and (ii) subsequent heat-treatment to remove the binder and solvents, and then bond the NiTi powders using liquid phase sintering via the formation of a transient NiTi-Nb eutectic phase. We investigate the effects of Nb concentration (0, 1.5, 3.

Three-Dimensional Printing of Cytocompatible, Thermally Conductive Hexagonal Boron Nitride Nanocomposites.

Hexagonal boron nitride (hBN) is a thermally conductive yet electrically insulating two-dimensional layered nanomaterial that has attracted significant attention as a dielectric for high-performance electronics in addition to playing a central role in thermal management applications. Here, we report a high-content hBN-polymer nanocomposite ink, which can be 3D printed to form mechanically robust, self-supporting constructs. In particular, hBN is dispersed in poly(lactic- co-glycolic acid) and 3D printed at room temperature through an extrusion process to form complex architectures.

3D-printing porosity: A new approach to creating elevated porosity materials and structures.

Unlabelled: We introduce a new process that enables the ability to 3D-print high porosity materials and structures by combining the newly introduced 3D-Painting process with traditional salt-leaching. The synthesis and resulting properties of three 3D-printable inks comprised of varying volume ratios (25:75, 50:50, 70:30) of CuSO salt and polylactide-co-glycolide (PLGA), as well as their as-printed and salt-leached counterparts, are discussed. The resulting materials are comprised entirely of PLGA (F-PLGA), but exhibit porosities proportional to the original CuSO content.

Three-Dimensional Printing and Tissue Engineering in Orthopaedics.

Additive manufacturing and three-dimensional printing technology may revolutionize tissue-engineering strategies. Many clinical needs, including multitissue regeneration, remain unmet among patients with orthopaedic conditions. Ongoing research efforts in three-dimensional printing, including cell-containing bioinks for bioprinting, have resulted in acellular and cellular biomaterials that may help regenerate or replace damaged or missing biologic tissues.

Applications of Three-Dimensional Printing in Orthopaedic Surgery.

Orthopaedic surgeons should be aware of the variety of applications of three-dimensional printing, which range from rough-and-ready applications, such as rapid prototyping of implant designs with the use of polymers to the fabrication of patient-specific implants and custom implants with the use of the principles of metallurgy. The local manufacture of low-cost prosthetic devices in third-world nations is the best example of the potential application of three-dimensional printing. Orthopaedic surgeons should understand the multiple applications of three-dimensional printing, including prototyping of anatomy, implants, orthotics, patient-specific instrumentation, and implants that incorporate porous structures and accommodate complex anatomy, as well as the future of biologically active three-dimensional printing.

Introduction to Additive Manufacturing and Three-Dimensional Printing in Orthopaedics.

Additive manufacturing involves the construction of devices via the layer-by-layer deposition of materials. Additive manufacturing, which also is referred to as three-dimensional printing, is different from traditional machining, which involves the subtraction of material from a workpiece. Although traditional machining methods have been used in the field of manufacturing for decades, a recent rise in the commercial use of additive manufacturing has occurred in the field of orthopaedic surgery.

3D printed hyperelastic "bone" scaffolds and regional gene therapy: A novel approach to bone healing.

The purpose of this study was to evaluate the viability of human adipose-derived stem cells (ADSCs) transduced with a lentiviral (LV) vector to overexpress bone morphogenetic protein-2 (BMP-2) loaded onto a novel 3D printed scaffold. Human ADSCs were transduced with a LV vector carrying the cDNA for BMP-2. The transduced cells were loaded onto a 3D printed Hyperelastic "Bone" (HB) scaffold.

"Tissue Papers" from Organ-Specific Decellularized Extracellular Matrices.

Using an innovative, tissue-independent approach to decellularized tissue processing and biomaterial fabrication, the development of a series of "tissue papers" derived from native porcine tissues/organs (heart, kidney, liver, muscle), native bovine tissue/organ (ovary and uterus), and purified bovine Achilles tendon collagen as a control from decellularized extracellular matrix particle ink suspensions cast into molds is described. Each tissue paper type has distinct microstructural characteristics as well as physical and mechanical properties, is capable of absorbing up to 300% of its own weight in liquid, and remains mechanically robust ( = 1-18 MPa) when hydrated; permitting it to be cut, rolled, folded, and sutured, as needed. In vitro characterization with human mesenchymal stem cells reveals that all tissue paper types support cell adhesion, viability, and proliferation over four weeks.

Robust and Elastic Lunar and Martian Structures from 3D-Printed Regolith Inks.

Here, we present a comprehensive approach for creating robust, elastic, designer Lunar and Martian regolith simulant (LRS and MRS, respectively) architectures using ambient condition, extrusion-based 3D-printing of regolith simulant inks. The LRS and MRS powders are characterized by distinct, highly inhomogeneous morphologies and sizes, where LRS powder particles are highly irregular and jagged and MRS powder particles are rough, but primarily rounded. The inks are synthesized via simple mixing of evaporant, surfactant, and plasticizer solvents, polylactic-co-glycolic acid (30% by solids volume), and regolith simulant powders (70% by solids volume).

Multi and mixed 3D-printing of graphene-hydroxyapatite hybrid materials for complex tissue engineering.

With the emergence of three-dimensional (3D)-printing (3DP) as a vital tool in tissue engineering and medicine, there is an ever growing need to develop new biomaterials that can be 3D-printed and also emulate the compositional, structural, and functional complexities of human tissues and organs. In this work, we probe the 3D-printable biomaterials spectrum by combining two recently established functional 3D-printable particle-laden biomaterial inks: one that contains hydroxyapatite microspheres (hyperelastic bone, HB) and another that contains graphene nanoflakes (3D-graphene, 3DG). We demonstrate that not only can these distinct, osteogenic, and neurogenic inks be co-3D-printed to create complex, multimaterial constructs, but that composite inks of HB and 3DG can also be synthesized.

Hyperelastic "bone": A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial.

Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB).

Functional Maturation of Induced Pluripotent Stem Cell Hepatocytes in Extracellular Matrix-A Comparative Analysis of Bioartificial Liver Microenvironments.

Unlabelled: : Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the influence of novel three-dimensional bioartificial microenvironments on function and maturation of hepatocyte-like cells differentiated from iPSCs and grown within an acellular, liver-derived extracellular matrix (ECM) scaffold.

Advancing the field of 3D biomaterial printing.

3D biomaterial printing has emerged as a potentially revolutionary technology, promising to transform both research and medical therapeutics. Although there has been recent progress in the field, on-demand fabrication of functional and transplantable tissues and organs is still a distant reality. To advance to this point, there are two major technical challenges that must be overcome.