3D-printed Bone Research Articles

Establishing stable and highly osteogenic hiPSC-derived MSCs for 3D-printed bone graft through microenvironment modulation by CHIR99021-treated osteocytes

Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal candidates for the production of standardised and scalable bioengineered bone grafts. However, stable induction and osteogenic differentiation of iMSCs pose challenges in the industry. We developed a precise differentiation method to produce homogeneous and fully differentiated iMSCs. In this study, we established a standardised system to prepare iMSCs with increased osteogenic potential and improved bioactivity by introducing a CHIR99021 (C91)-treated osteogenic microenvironment (COOME). COOME enhances the osteogenic differentiation and mineralisation of iMSCs via canonical Wnt signalling. Global transcriptome analysis and co-culturing experiments indicated that COOME increased the pro-angiogenesis/neurogenesis activity of iMSCs. The superior osteogenic differentiation and mineralisation abilities of COOME-treated iMSCs were also confirmed in a Bio3D module generated using a polycaprolactone (PCL) and cell-integrated 3D printing (PCI3D) system, which is the closest model to in vivo research. This COOME-treated iMSCs differentiation system offers a new perspective for generating highly osteogenic, bioactive, and anatomically matched grafts for clinical applications. Statement of significanceAlthough human induced pluripotent stem cell-derived MSCs (iMSCs) are ideal seed cells for synthetic bone implants, the challenges of stable induction and osteogenic differentiation hinder their clinical application. This study established a standardised system for the scalable preparation of iMSCs with improved osteogenic potential by combining our precise iMSC differentiation method with the CHIR99021 (C91)-treated osteocyte osteogenic microenvironment (COOME) through the activation of canonical Wnt signalling. Moreover, COOME upregulated the pro-angiogenic and pro-neurogenic capacities of iMSCs, which are crucial for the integration of implanted bone grafts. The superior osteogenic ability of COOME-treated iMSCs was confirmed in Bio3D modules generated using PCL and cell-integrated 3D printing systems, highlighting their functional potential in vivo. This study contributes to tissue engineering by providing insights into the functional differentiation of iMSCs for bone regeneration.

Developing a production workflow for 3D-printed temporal bone surgical simulators

Introduction3D-printed temporal bone models enable the training and rehearsal of complex otological procedures. To date, there has been no consolidation of the literature regarding the developmental process of 3D-printed temporal bone models. A brief review of the current literature shows that many of the key surgical landmarks of the temporal bone are poorly represented in models. This study aims to propose a novel design and production workflow to produce high-fidelity 3D-printed temporal bone models for surgical simulation.MethodsDevelopmental phases for data extraction, 3D segmentation and Computer Aided Design (CAD), and fabrication are outlined. The design and fabrication considerations for key anatomical regions, such as the mastoid air cells and course of the facial nerve, are expounded on with the associated strategy and design methods employed. To validate the model, radiological measurements were compared and a senior otolaryngologist performed various surgical procedures on the model.ResultsMeasurements between the original scans and scans of the model demonstrate sub-millimetre accuracy of the model. Assessment by the senior otologist found that the model was satisfactory in simulating multiple surgical procedures.ConclusionThis study offers a systematic method for creating accurate 3D-printed temporal bone models for surgical training. Results show high accuracy and effectiveness in simulating surgical procedures, promising improved training and patient outcomes.

Biomechanical comparison of bone staple fixation methods with suture material for median sternotomy closure using 3D-printed bone models

ABSTRACT Aim To compare the biomechanical properties of three different sternal closure techniques in a 3D-printed bone model of a sternum from a 30-kg dog. Methods Median sternotomy was performed on a total of 90 three-dimensional (3D) copies of a polycarbonate (PC) model of a sternum, generated from the CT images of the sternum of a 30-kg German Shepherd dog. Three different methods were used to repair the sternotomies: polydioxanone suture (group PDS, n = 30), stainless steel bone staples (group SS, n = 30), and nitinol bone staples (group NS, n = 30). Each repair method was tested by applying tensile force in one of three ways (longitudinally, laterally, or torsionally) resulting in a sample size of n = 10 for each repair method-loading combination. In all experiments, the loads at 1-mm and 2-mm gap formation, failure, and the displacement at the failure point were measured. Results In lateral distraction and longitudinal shear tests, NS and SS staple repairs required application of significantly greater force than PDS across all displacement criteria (1 and 2 mm). NS exhibited significantly greater failure load than PDS. In torsion tests, NS required significantly greater application of force compared to SS or PDS at all displacement criteria (1 and 2 mm) and exhibited a greater failure load than PDS. In terms of displacement at failure point, PDS suture showed more displacement than SS or NS across all experiments (laterally, longitudinally, torsionally). Conclusions In this study, bone staples were mechanically superior to PDS suture in median sternotomy closure using 3D-printed bone model in terms of 1-mm, 2-mm displacement loads, and displacement at failure. NS had a higher failure load than PDS under lateral, longitudinal, and torsional distraction. Clinical relevance These study results imply that bone staples can be considered as an alternative surgical method for median sternotomy closure in dogs.

A Sensorized 3D-Printed Knee Test Rig for Preliminary Experimental Validation of Patellar Tracking and Contact Simulation.

Experimental validation of computational simulations is important because it provides empirical evidence to verify the accuracy and reliability of the simulated results. This validation ensures that the simulation accurately represents real-world phenomena, increasing confidence in the model's predictive capabilities and its applicability to practical scenarios. The use of musculoskeletal models in orthopedic surgery allows for objective prediction of postoperative function and optimization of results for each patient. To ensure that simulations are trustworthy and can be used for predictive purposes, comparing simulation results with experimental data is crucial. Although progress has been made in obtaining 3D bone geometry and estimating contact forces, validation of these predictions has been limited due to the lack of direct in vivo measurements and the economic and ethical constraints associated with available alternatives. In this study, an existing commercial surgical training station was transformed into a sensorized test bench to replicate a knee subject to a total knee replacement. The original knee inserts of the training station were replaced with personalized 3D-printed bones incorporating their corresponding implants, and multiple sensors with their respective supports were added. The recorded movement of the patella was used in combination with the forces recorded by the pressure sensor and the load cells, to validate the results obtained from the simulation, which was performed by means of a multibody dynamics formulation implemented in a custom-developed library. The utilization of 3D-printed models and sensors facilitated cost-effective and replicable experimental validation of computational simulations, thereby advancing orthopedic surgery while circumventing ethical concerns.

Mechanistic study on the role of 3D-Printed biomimetic coral bone scaffolds in bone defect repair

With the continuous innovation and development of 3D printing technology, 3D-printed biomimetic coral bone scaffolds have demonstrated significant potential in the field of bone defect repair. This paper aims to explore in-depth the mechanistic study of 3D-printed biomimetic coral bone scaffolds in bone defect repair, by systematically reviewing relevant literature and analyzing their potential mechanisms in promoting bone growth and improving the success rate of bone defect repair. Firstly, this paper introduces the fabrication process and material characteristics of 3D-printed biomimetic coral bone scaffolds. Secondly, the paper discusses the mechanisms of 3D-printed biomimetic coral bone scaffolds in terms of biocompatibility, biomechanical performance, as well as their roles in vascularization and bone formation. Finally, the paper outlines future research directions for 3D-printed biomimetic coral bone scaffolds, including further optimization of material properties, improvement of printing precision, and expansion of clinical applications.

Minimally Invasive Plate Osteosynthesis (MIPO) of Comminuted Radial Fractures Using a Locking Plate Contoured on a 3D-Printed Model of the Feline Antebrachium: A Cadaveric Study.

(1) Background: Due to the unique structural and functional characteristics of the forelimb in cats, fractures of the radius and ulna are best repaired using internal fixation and stabilization in accordance with AO principles. This study presents the results of reduction of 42 cadaveric comminuted feline radial fractures reduced by minimally invasive plate osteosynthesis (MIPO). (2) Methods: Radius fractures were created on 21 pairs of forelimbs with intact bones. MIPO was then performed using two locking bone plates pre-contoured on 3D-printed bone models of the antebrachium of a male and a female cat. Pre- and postoperative radiographs were taken, and radius length and anatomical lateral distal radial angle (aLDRA) were measured. (3) Results: All fractures were classified as complex diaphyseal fractures of the radius. The radial bone length did not change significantly after surgery (F1,18 = 0.01, p = 0.933). However, the aLDRA was modified after surgery (F1,18 = 7.51, p = 0.013), but this change was only observed in females, in whom the aLDRA was significantly reduced (p = 0.035) compared to the value determined by the shape of the plate. In males, the pre- and postoperative aLDRA values were similar (p = 0.824). In 40 cases, alignment, adjacency of bone fragments, and apparatus were judged to be satisfactory. In two cases, the plate was fixed to the proximal radius and distal ulna due to misidentification of the distal radius. In both cases, revision surgery and correct fixation of the radius gave proper alignment, adjacency, and apparatus. (4) Conclusion: A pre-contoured plate on a 3D-printed model of the male and female domestic cat antebrachium was suitable for the reduction and stabilization of comminuted radial fractures in a cohort of domestic cat cadavers without the need to print individual antebrachial bone models for each patient.

A metamaterial bone plate for biofixation based on 3D printing technology

Bone plate design and production methods are critical for producing metamaterial bone plates. This study investigated the design and development process of porous structures and metamaterial bone plates for biofixation applications. We designed the porous structures for bone plates using parametric modeling and fused them via the implicit surface fusion method. Likewise, we designed the metamaterial bone plate structure using reverse reconstruction and topological optimization. Thereafter, we utilized three-dimensional (3D) printing for producing and post-processing the metamaterial bone plate. We observed a reduced stress-shielding effect after topological optimization. Additionally, the resultant diamond porous structure maintained a high porosity under pressure. The 3D-printed bone plates and fillers had a bright porous surface, with clear pore structures and good connectivity. The assembly of the 3D-printed femur, bone plate, filler, and standardized screw indicated a good fitting, and the filler could be fixed by the inclined surface. Taken together, the findings of this study established the foundation for the prospective application of metamaterial bone plates in biofixation.

A new 3D-printed temporal bone: ‘the SAPIENS’—specific anatomical printed-3D-model in education and new surgical simulations

PurposeOtology and neuro-otology surgeries pose significant challenges due to the intricate and variable anatomy of the temporal bone (TB), requiring extensive training. In the last years 3D-printed temporal bone models for otological dissection are becoming increasingly popular. In this study, we presented a new 3D-printed temporal bone model named 'SAPIENS', tailored for educational and surgical simulation purposes.MethodsThe 'SAPIENS' model was a collaborative effort involving a multidisciplinary team, including radiologists, software engineers, ENT specialists, and 3D-printing experts. The development process spanned from June 2022 to October 2023 at the Department of Sense Organs, Sapienza University of Rome.Acquisition of human temporal bone images; temporal bone rendering; 3D-printing; post-printing phase; 3D-printed temporal bone model dissection and validation.ResultsThe 'SAPIENS' 3D-printed temporal bone model demonstrated a high level of anatomical accuracy, resembling the human temporal bone in both middle and inner ear anatomy. The questionnaire-based assessment by five experienced ENT surgeons yielded an average total score of 49.4 ± 1.8 out of 61, indicating a model highly similar to the human TB for both anatomy and dissection. Specific areas of excellence included external contour, sigmoid sinus contour, cortical mastoidectomy simulation, and its utility as a surgical practice simulator.ConclusionWe have designed and developed a 3D model of the temporal bone that closely resembles the human temporal bone. This model enables the surgical dissection of the middle ear and mastoid with an excellent degree of similarity to the dissection performed on cadaveric temporal bones.

In vitro evaluation of bone cell response to novel 3D-printable nanocomposite biomaterials for bone reconstruction.

Critically-sized segmental bone defects represent significant challenges requiring grafts for reconstruction. 3D-printed synthetic bone grafts are viable alternatives to structural allografts if engineered to provide appropriate mechanical performance and osteoblast/osteoclast cell responses. Novel 3D-printable nanocomposites containing acrylated epoxidized soybean oil (AESO) or methacrylated AESO (mAESO), polyethylene glycol diacrylate, and nanohydroxyapatite (nHA) were produced using masked stereolithography. The effects of volume fraction of nHA and methacrylation of AESO on interactions of differentiated MC3T3-E1 osteoblast (dMC3T3-OB) and differentiated RAW264.7 osteoclast cells with 3D-printed nanocomposites were evaluated in vitro and compared with a control biomaterial, hydroxyapatite (HA). Higher nHA content and methacrylation significantly improved the mechanical properties. All nanocomposites supported dMC3T3-OB cells' adhesion and proliferation. Higher amounts of nHA enhanced cell adhesion and proliferation. mAESO in the nanocomposites resulted in greater adhesion, proliferation, and activity at day 7 compared with AESO nanocomposites. Excellent osteoclast-like cells survival, defined actin rings, and large multinucleated cells were only observed on the high nHA fraction (30%) mAESO nanocomposite and the HA control. Thus, mAESO-based nanocomposites containing higher amounts of nHA have better interactions with osteoblast-like and osteoclast-like cells, comparable with HA controls, making them a potential future alternative graft material for bone defect repair.

467 Enhancing Cell Infiltration and Controlled Growth Factor Release for a Customized 3D-Printed Bone Graft Composite

OBJECTIVES/GOALS: Annually, 1.5 million global patients receive maxillofacial reconstruction. The gold standard, involving bone particulate, lacks reproducibility. To improve this, we have developed a custom 3D-printable, porous cover-core design. This study optimizes the hydrogel core properties and growth factor (GF) release for enhanced bone regeneration. METHODS/STUDY POPULATION: Different ratios of Methacrylated Gelatin (GelMa), Methacrylated Alginate (AlgMa) and tricalcium phosphate (α²-TCP) were combined to optimize cell viability, GF sequestration and mechanical stability. Material characterization was performed using a rheometer to determine the viscoelastic properties of the blends. Release from disks loaded with FGF-containing PLGA microparticles was quantified with an ELISA kit. Furthermore, scanning electron microscopy (SEM) was conducted to quantify hydrogel porosity. In vitro studies were performed using NIH 3T3 murine fibroblasts in Corning Transwells while immunofluorescent, metabolic and osteogenic studies were performed in 96 well plates to investigate cell infiltration, cell adhesion, viability and differentiation, respectively. RESULTS/ANTICIPATED RESULTS: By adjusting the AlgGelMa ratio, we manipulated matrix properties. GelMa possesses excellent durability and cell adhesion due to intrinsic RGD-binding motifs. AlgMa enhanced swelling by 30%, growth factor sequestration by 50% in 24hrs, and matrix storage modulus without increasing the loss modulus which could cause cell migration away from the hydrogel. Varying the AlgGelMa ratio lowered pH, promoted cell infiltration, and reduced fibronectin accumulation. The addition of β-TCP is anticipated to improve cell differentiation towards an osteogenic lineage due to improved elastic modulus, calcium and phosphate ion concentration improving mineral deposition. DISCUSSION/SIGNIFICANCE: These findings suggest through the use of this composite, early cell infiltration can be increased and promoted due to FGF release, leading to increased osteointegration. Our porous cover-core design ensures efficient clot integration and early cell infiltration, enhancing osteointegration through FGF release.

Moving Beyond the Temporal Bone Lab: Creating a Drilling Station in the Otolaryngology Clinic.

With the advent of operable 3-dimensional (3D)-printed models, case preparation could occur outside of the cadaveric laboratory. The objective of this study was to design a mobile drilling station that can be used for surgical practice in a variety of clean workplaces. Using materials obtained from hardware stores and online retailers, a wheelable drilling station was constructed to mimic laboratory conditions while also being easily maneuverable into clinic rooms. The station houses the otologic drill, suction, and irrigation mechanisms, is height adjustable, and has a shielded workspace. The mobile drilling station was moved into a microscope-containing otolaryngology clinic room where faculty and trainees were asked to drill a pediatric 3D-printed temporal bone followed by completing an evaluation survey. This is the first mobile drilling station described in the literature and can be easily constructed, mobilized, and used in an otolaryngology clinic for dedicated surgical practice using 3D-printed models.

3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration

Although several bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules for enhanced bone regeneration have been recently developed, the manipulation of on-demand release profiles of different biomolecules during bone regeneration remains challenging. Herein, a 3D-printed dual-drug-loaded biomimetic scaffold to regulate the host stem cell recruitment and osteogenic differentiation in a two-stage process for bone regeneration was successfully fabricated. First, a chemotactic small-molecule drug, namely, simvastatin (SIM) was directly incorporated into the hydroxyapatite/collagen bioink for printing and could be rapidly released during the early stage of bone regeneration. Further, near-infrared (NIR)-light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the osteogenic drug, i.e., pargyline (PGL) in a controllable manner. Together, our scaffold displayed an on-demand sequential release of those two drugs and could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models. Altogether, this scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.

Advanced Bioresin Formulation for 3D-Printed Bone Scaffolds: PCLDMA and p-PLA Integration.

In bone tissue engineering, scaffold attributes such as pore dimensions and mechanical strength are crucial. This study synthesized polycaprolactone dimethacrylate (PCLDMA) from polycaprolactone (PCL), incorporating epichlorohydrin (Epi-PCL) and methacryloyl chloride (Meth-Cl). PCLDMA was blended with polylactic acid (p-PLA) to 3D-print bone scaffolds using stereolithography (SLA). Analytical techniques included nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and compression testing. Degradation kinetics and cell viability were investigated using human osteoblast (HOB) cells. Findings revealed PCLDMA/p-PLA composite scaffold superiority over the original polymers. Notably, PCLDMA-60 (60% PCLDMA, 40% p-PLA) displayed optimal properties. Compressive strength varied from 0.019 to 16.185 MPa, porosity from 2% to 50%, and degradation rates from 0% to 0.4% over three days. Cell viability assays affirmed biocompatibility across various PCLDMA ratios. In conclusion, PCLDMA/p-PLA composite scaffolds, particularly PCLDMA-60, show great potential in bone tissue engineering.

Techniques, mechanisms, and application of 3D-printed biodegradable metals for bone regeneration

Repairing severe bone defects and restoring complete bone tissue morphology are major challenges in clinical practice. Biodegradable metals (BMs) are bioactive materials with active degradation properties. The gradual improvement of three-dimensional (3D) printing technology holds tremendous potential for development and has spurred on the growing utilization of 3D-printed BM materials in the clinical applications of bone regeneration. In this paper, we review the application of three BM (magnesium, iron, and zinc) materials for use in 3D-printed bone regeneration; define the principle of 3D-printed bone regeneration, including the method and selection of materials; and summarize the characteristics and uses of various printing technologies and the properties, advantages, and disadvantages of BMs. Compared to traditional nondegradable implants, 3D-printed degradable metal implants have the advantages of not leaving residue, avoiding stress shielding, promoting osteogenesis and vascularization, and exhibiting antimicrobial ability. In addition, we summarize the clinical applications of 3D-printed BMs. 3D-printed BMs can be used not only for fracture fixation and bone defect repair but also for osteoporotic fracture repair, cartilage repair, maxillofacial surgery, and other processes. In this article, we discuss the advantages and limitations of the current 3D printing degradable metallic materials and describe future development prospects.

Customized three-dimensional printed ceramic bone grafts for osseous defects: a prospective randomized study

Ridge resorption can result in insufficient bone volume for implant surgery, necessitating bone substitutes to restore the resorption area. Recent advances in computer-aided design and manufacturing enable the use of alloplastic bone graft materials with customizable compositions or shapes. This randomized study evaluated the clinical effectiveness of a customized three-dimensional (3D) printed alloplastic bone material. Sixty patients requiring guided bone regeneration for implant installation following tooth extraction due to alveolar bone resorption were recruited at two institutions. The participants were randomly allocated to either a group that received 3D-printed patient-customized bone graft material or a group that received conventional block bone graft material. Implant installation with bone harvesting was performed approximately 5 months after bone grafting. Histological and radiological assessments of the harvested bone area were performed. The experimental group had a significantly higher percent bone volume and a smaller tissue surface than the control group. Bone volume, bone surface, bone surface/volume ratio, bone surface density (bone surface/total volume), and bone mineral density did not differ significantly between groups. Patient-customized bone graft materials offer convenience and reduce patient discomfort. The findings suggest 3D-printed patient-customized bone graft materials could be used as an alternative for simpler bone grafting procedures.

Deeply Implanted Conformal Antenna for Real-Time Bio-Telemetry Applications.

The design and experimental verification of a deeply implanted conformal printed antenna is presented. The hip implant acts as the ground plane for a coaxial-cable-fed trapezoidal radiator designed to transmit biological signals collected within the body by proper biosensors. The arrangement, consisting of a metallic (or equivalent) hip implant, bio-compatible gypsum-based dielectric, and conformal radiator, was tested when the hosting 3D-printed plastic bone was immersed in tissue-like liquid contained in a plastic bucket. The dimensions of the set-up are similar to a human leg. Matching and radiation characteristics are presented in the industrial, scientific, and medical (ISM) frequency band (2.4-2.5 GHz), showing the feasibility of the proposed arrangement.

Three-dimension deformation measurement using modified microscopic stereo-vision technology

An improved microscopic stereo-vision technology was developed for microscopic deformation (displacement and strain) measurement. First, the distortion of the microscope lens is significant, but the existing internal parameters calibration approach is prone to abnormal calibration results due to the parameter coupling. An innovative calibration method based on a modified homography transformation model is proposed. Second, the short working distance and the stereo angle of the two cameras lead to the degradation of image quality, and the correlation analysis is challenged. The genetic algorithm (GA) was modified and introduced in three-dimensional digital image correlation (3D-DIC) to help search for more accurate initial values of the displacement. The proposed GA-assisted DIC shows higher subpixel precision and speed in the image-matching test. Then, the developed microscopic stereo-vision technology incorporating the above innovative innovations is applied to a mechanical properties experiment with a 3D-printed artificial bone scaffold.

Evaluating the effect of pore size for 3d-printed bone scaffolds

The present study investigated the influence of pore size of strut-based Diamond and surface-based Gyroid structures for their suitability as medical implants. Samples were made additively from laser powder bed fusion process with a relative density of 0.3 and pore sizes ranging from 300 to 1300 μm. They were subsequently examined for their manufacturability and mechanical properties. In addition, non-Newtonian computational fluid dynamics and discrete phase models were conducted to assess pressure drop and cell seeding efficiency. The results showed that both Diamond and Gyroid had higher as-built densities with smaller pore sizes. However, Gyroid demonstrated better manufacturability as its relative density was closer to the as-designed one. In addition, based on mechanical testing, the elastic modulus was largely unaffected by pore size, but post-yielding behaviors differed, especially in Diamond. High mechanical sensitivity in Diamond could be explained partly by Finite Element simulations, which revealed stress localization in Diamond and more uniform stress distribution in Gyroid. Furthermore, we defined the product of the normalized specific surface, normalized pressure drop, and cell seeding efficiency as the indicator of an optimal pore size, in which this factor identified an optimal pore size of approximately 500 μm for both Diamond and Gyroid. Besides, based on such criterion, Gyroid exhibited greater applicability as bone scaffolds. In summary, this study provides comprehensive assessment of the effect of pore size and demonstrates the efficient estimation of an in-silico framework for evaluating lattice structures as medical implants, which could be applied to other lattice architectures.

Additively manufactured porous scaffolds by design for treatment of bone defects.

There has been increasing attention to produce porous scaffolds that mimic human bone properties for enhancement of tissue ingrowth, regeneration, and integration. Additive manufacturing (AM) technologies, i.e., three dimensional (3D) printing, have played a substantial role in engineering porous scaffolds for clinical applications owing to their high level of design and fabrication flexibility. To this end, this review article attempts to provide a detailed overview on the main design considerations of porous scaffolds such as permeability, adhesion, vascularisation, and interfacial features and their interplay to affect bone regeneration and osseointegration. Physiology of bone regeneration was initially explained that was followed by analysing the impacts of porosity, pore size, permeability and surface chemistry of porous scaffolds on bone regeneration in defects. Importantly, major 3D printing methods employed for fabrication of porous bone substitutes were also discussed. Advancements of MA technologies have allowed for the production of bone scaffolds with complex geometries in polymers, composites and metals with well-tailored architectural, mechanical, and mass transport features. In this way, a particular attention was devoted to reviewing 3D printed scaffolds with triply periodic minimal surface (TPMS) geometries that mimic the hierarchical structure of human bones. In overall, this review enlighten a design pathway to produce patient-specific 3D-printed bone substitutions with high regeneration and osseointegration capacity for repairing large bone defects.

3D-bioprinted bone scaffolds incorporating SR1 nanoparticles enhance blood vessel regeneration in rat calvarial defects

The inherent limitations of bone grafting in the treatment of critical-sized bone defects have led to a growing demand for bone repair implants. Three-dimensional (3D) bioprinting has emerged as a promising manufacturing technique for implants, offering flexibility in their structural design and the use of applicable materials. Although numerous 3D-bioprinted bone scaffolds have been developed to enhance osteogenesis, angiogenesis remains a challenge. Angiogenesis is crucial for successful bone healing because the process forms blood vessels to deliver essential nutrients and oxygen. Endothelial progenitor cells (EPCs) play a pivotal role in the early stages of vascularization. These cells, capable of differentiating into endothelial cells (ECs), are recruited from the bone marrow to the injured area during the healing process. CD34+ cells, a subset of EPCs, have gained attention because of their neovascularization potential and ability to contribute to bone regeneration. The incorporation of CD34+ cell-enhancing factors into 3D-printed bone scaffolds may facilitate successful bone healing in critical defects. StemRegenin-1 (SR1), a molecule that promotes CD34+ cell expansion, has shown promising results in increasing CD34+ hematopoietic stem and progenitor cell populations. This study aimed to investigate the sustained release of SR1 from a collagen-based scaffold integrated with mesoporous silica nanoparticles (MSNs) to promote angiogenesis and enhance bone healing. The sustained release of SR1 from the collagen scaffold is hypothesized to promote angiogenesis, thereby facilitating bone repair. In vitro studies have demonstrated the angiogenic potential of SR1; however, further in vivo investigations are required to establish its clinical efficacy. This study contributes to the development of novel therapies targeting CD34+ cells and demonstrates the potential of SR1 as a promising agent for promoting angiogenesis and enhancing bone healing in critical defects.