Effect of Morphological Characteristics and Biomineralization of 3D-Printed Gelatin/Hyaluronic Acid/Hydroxyapatite Composite Scaffolds on Bone Tissue Regeneration

The use of porous three-dimensional (3D) composite scaffolds has attracted great attention in bone tissue engineering applications because they closely simulate the major features of the natural extracellular matrix (ECM) of bone. This study aimed to prepare biomimetic composite scaffolds via a simple 3D printing of gelatin/hyaluronic acid (HA)/hydroxyapatite (HAp) and subsequent biomineralization for improved bone tissue regeneration. The resulting scaffolds exhibited uniform structure and homogeneous pore distribution. In addition, the microstructures of the composite scaffolds showed an ECM-mimetic structure with a wrinkled internal surface and a porous hierarchical architecture. The results of bioactivity assays proved that the morphological characteristics and biomineralization of the composite scaffolds influenced cell proliferation and osteogenic differentiation. In particular, the biomineralized gelatin/HA/HAp composite scaffolds with double-layer staggered orthogonal (GEHA20-ZZS) and double-layer alternative structure (GEHA20-45S) showed higher bioactivity than other scaffolds. According to these results, biomineralization has a great influence on the biological activity of cells. Hence, the biomineralized composite scaffolds can be used as new bone scaffolds in bone regeneration.     

3D Printed SiOC(N) Ceramic Scaffolds for Bone Tissue Regeneration: Improved Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone, these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy, and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.     

Biomimetic Polycaprolactone-Graphene Oxide Composites for 3D Printing Bone Scaffolds

Bone shows a radial gradient architecture with the exterior densified cortical bone and the interior porous cancellous bone. However, previous studies presented uniform designs for bone scaffolds that do not mimic natural bone's gradient structure. Hence, mimicking native bone structures is still challenging in bone tissue engineering. In this study, a novel biomimetic bone scaffold with Haversian channels is designed, which approximates mimicking the native bone structure. Also, the influence of adding graphene oxide (GO) to polycaprolactone (PCL)-based scaffolds are investigated by preparing PCL/GO composite ink containing 0.25% and 0.75% GO and then 3D printing scaffolds by an extrusion-based machine. Scanning electron microscopy (SEM) is used for morphological analysis. SEM reveals good printability and interconnected pore structure. The contact angle test shows that wettability reinforces with the increase of GO content. The mechanical behavior of the scaffolds under compression is examined numerically and experimentally. The results indicate that incorporation of GO can affect bone scaffolds' Young's modulus and von Mises stress distribution. Moreover, the biodegradation rates accelerate in the PCL/GO scaffolds. Biological characterizations, such as cell growth, viability, and attachment, are performed utilizing osteoblast cells. Compared to pure PCL, an enhancement is observed in cell viability in the PCL/GO scaffolds.     

Cryo-3D Printing of Hierarchically Porous Polyhydroxymethylene Scaffolds for Hard Tissue Regeneration

High molecular weight polyhydroxymethylene (PHM) has a repeat unit identical to that of low molecular weight sugar alcohols and exhibits carbohydrate-like properties. Herein, cryogenic extrusion-based 3D printing is combined with a phase separation in water to fabricate hierarchically porous PHM scaffolds containing interconnected macro-, micro-, and nanopores. As PHM is infusible and insoluble in common solvents, its precursor polyvinylene carbonate (PVCA) dissolved in dimethylsulfoxide (DMSO) is used to 3D print hierarchically porous PVCA scaffolds that are converted into PHM by hydrolysis without impairing the pore architectures. Similar to low-temperature deposition manufacturing, the PVCA/DMSO freezes on a build platform at −78 °C. However, instead of removing the frozen solvent by sublimation, the frozen scaffold is immersed in water to recover DMSO and to effect phase separation by precipitation. However, the computer-guided printhead pathway controls macropore formation phase separation of frozen PVCA/DMSO upon contact with water accounts for simultaneous micro- and nanopore formation. Contrary to 3D printing of PVCA/DMSO at ambient temperature, this cryo-3D printing process does not require shear thinning additives and affords significantly improved build precision with macropore sizes variable between 200 and 1500 µm. Cryo-3D-printed PHM scaffolds are biocompatible and promote osteoblast proliferation.     

Fiber-Based Composite Tissue Engineering Scaffolds for Drug Delivery

Drug delivery through tissue-engineered scaffolds provides a composite approach to address the regenerative limitations of simple material implantation, providing expanded avenues for therapeutic tissue-repair strategies in the clinic. Both nano- and microfibrous scaffolds generated by a variety of techniques have been investigated for their potential in drug-delivery applications. While nanofibers mimic the structure and organization of natural extracellular matrix, microfibers provide more sustained release of drugs, larger pores to facilitate cell infiltration, and improved mechanical support. Various methods exist to embed drugs within the fiber matrix to modulate the release kinetics specific to the tissue-engineering application. The current article reviews the established and emerging fabrication methods for drug-loaded fiber-based scaffolds and addresses how further combination into composite scaffolds can enhance drug delivery and tissue regeneration.     

Application of 3D-Printed,PLGA-Based Scaffolds in Bone Tissue Engineering

Polylactic acid–glycolic acid (PLGA) has been widely used in bone tissue engineering due to its favorable biocompatibility and adjustable biodegradation. 3D printing technology can prepare scaffolds with rich structure and function, and is one of the best methods to obtain scaffolds for bone tissue repair. This review systematically summarizes the research progress of 3D-printed, PLGA-based scaffolds. The properties of the modified components of scaffolds are introduced in detail. The influence of structure and printing method change in printing process is analyzed. The advantages and disadvantages of their applications are illustrated by several examples. Finally, we briefly discuss the limitations and future development direction of current 3D-printed, PLGA-based materials for bone tissue repair.     

Fabrication of Gentamicin Sulfate-Loaded 3D-Printed Polyvinyl Alcohol/Sodium Alginate/Gelatin-Methacryloyl Hybrid Scaffolds for Skin Tissue Replacement

3D-printed scaffolds can better mimic the function of human skin, both biologically and mechanically. Within the scope of this study, the effect of the addition of different amounts (10, 15, 20 mg) of gentamicin sulfate (GS) to a 10 mL solution of natural and synthetic polymers is investigated. Sodium alginate (SA), gelatin-methacryloyl (GelMA), and polyvinyl alcohol (PVA) are chosen as bioactive materials. The surface morphology and pore structures are visualized by scanning electron microscopy (SEM). According to the results, it is observed that the pore sizes of all scaffolds are smaller than 270 µm, the lowest value (130 µm) is obtained in the scaffold loaded with 15 mg GS, and it also has the highest tensile strength value (12.5 ± 7.6 MPa). Similarly, it is observed that the tensile strength (9.7 ± 4.5 MPa) is high in scaffold loaded with 20 mg GS. The biocompatibility test is performed with fibroblast cells, and the results show that the scaffolds are biocompatible with cells. The antibacterial test is carried out against the S.aureous and E. coli and the results indicate that all GS-loaded scaffolds demonstrate antibacterial activity.     

Ex Vivo and In Vivo Analyses of Novel 3D-Printed Bone Substitute Scaffolds Incorporating Biphasic Calcium Phosphate Granules for Bone Regeneration

(1) Background: The aim of this study was examining the ex vivo and in vivo properties of a composite made from polycaprolactone (PCL) and biphasic calcium phosphate (BCP) (synprint, ScientiFY GmbH) fabricated via fused deposition modelling (FDM); (2) Methods: Scaffolds were tested ex vivo for their mechanical properties using porous and solid designs. Subcutaneous implantation model analyzed the biocompatibility of PCL + BCP and PCL scaffolds. Calvaria implantation model analyzed the osteoconductive properties of PCL and PCL + BCP scaffolds compared to BCP as control group. Established histological, histopathological and histomorphometrical methods were performed to evaluate new bone formation.; (3) Results Mechanical testing demonstrated no significant differences between PCL and PCL + BCP for both designs. Similar biocompatibility was observed subcutaneously for PCL and PCL + BCP scaffolds. In the calvaria model, new bone formation was observed for all groups with largest new bone formation in the BCP group, followed by the PCL + BCP group, and the PCL group. This finding was influenced by the initial volume of biomaterial implanted and remaining volume after 90 days. All materials showed osteoconductive properties and PCL + BCP tailored the tissue responses towards higher cellular biodegradability. Moreover, this material combination led to a reduced swelling in PCL + BCP; (4) Conclusions: Altogether, the results show that the newly developed composite is biocompatible and leads to successful osteoconductive bone regeneration. The new biomaterial combines the structural stability provided by PCL with bioactive characteristics of BCP-based BSM. 3D-printed BSM provides an integration behavior in accordance with the concept of guided bone regeneration (GBR) by directing new bone growth for proper function and restoration.     

Additive Manufacturing of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Poly(D,L-lactide-co-glycolide) Biphasic Scaffolds for Bone Tissue Regeneration

Polyhydroxyalkanoates are biopolyesters whose biocompatibility, biodegradability, environmental sustainability, processing versatility, and mechanical properties make them unique scaffolding polymer candidates for tissue engineering. The development of innovative biomaterials suitable for advanced Additive Manufacturing (AM) offers new opportunities for the fabrication of customizable tissue engineering scaffolds. In particular, the blending of polymers represents a useful strategy to develop AM scaffolding materials tailored to bone tissue engineering. In this study, scaffolds from polymeric blends consisting of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(D,L-lactide-co-glycolide) (PLGA) were fabricated employing a solution-extrusion AM technique, referred to as Computer-Aided Wet-Spinning (CAWS). The scaffold fibers were constituted by a biphasic system composed of a continuous PHBV matrix and a dispersed PLGA phase which established a microfibrillar morphology. The influence of the blend composition on the scaffold morphological, physicochemical, and biological properties was demonstrated by means of different characterization techniques. In particular, increasing the content of PLGA in the starting solution resulted in an increase in the pore size, the wettability, and the thermal stability of the scaffolds. Overall, in vitro biological experiments indicated the suitability of the scaffolds to support murine preosteoblast cell colonization and differentiation towards an osteoblastic phenotype, highlighting higher proliferation for scaffolds richer in PLGA.     

3D Printable Composite Biomaterials Based on GelMA and Hydroxyapatite Powders Doped with Cerium Ions for Bone Tissue Regeneration

The main objective was to produce 3D printable hydrogels based on GelMA and hydroxyapatite doped with cerium ions with potential application in bone regeneration. The first part of the study regards the substitution of Ca²⁺ ions from hydroxyapatite structure with cerium ions (Ca_10-xCe_x(PO₄)₆(OH)₂, xCe = 0.1, 0.3, 0.5). The second part followed the selection of the optimal concentration of HAp doped, which will ensure GelMA-based scaffolds with good biocompatibility, viability and cell proliferation. The third part aimed to select the optimal concentrations of GelMA for the 3D printing process (20%, 30% and 35%). In vitro biological assessment presented the highest level of cell viability and proliferation potency of GelMA-HC5 composites, along with a low cytotoxic potential, highlighting the beneficial effects of cerium on cell growth, also supported by Live/Dead results. According to the 3D printing experiments, the 30% GelMA enriched with HC5 was able to generate 3D scaffolds with high structural integrity and homogeneity, showing the highest suitability for the 3D printing process. The osteogenic differentiation experiments confirmed the ability of 30% GelMA-3% HC5 scaffold to support and efficiently maintain the osteogenesis process. Based on the results, 30% GelMA-3% HC5 3D printed scaffolds could be considered as biomaterials with suitable characteristics for application in bone tissue engineering.     

Bone Regeneration of a 3D-Printed Alloplastic and Particulate Xenogenic Graft with rhBMP-2

This study aimed to evaluate the bone regeneration capacity of a customized alloplastic material and xenograft with recombinant human bone morphogenetic protein-2 (rhBMP-2). We prepared hydroxyapatite (HA)/tricalcium phosphate (TCP) pure ceramic bone blocks made using a 3D printing system and added rhBMP-2 to both materials. In eight beagle dogs, a total of 32 defects were created on the lower jaws. The defective sites of the negative control group were left untreated (N group; 8 defects), and those in the positive control group were filled with particle-type Bio-Oss (P group; 12 defects). The defect sites in the experimental group were filled with 3D-printed synthetic bone blocks (3D group; 12 defects). Radiographic and histological evaluations were performed after healing periods of 6 and 12 weeks and showed no significant difference in new bone formation and total bone between the P and 3D groups. The 3D-printed custom HA/TCP graft with rhBMP-2 showed bone regeneration effects similar to that of particulate Bio-Oss with rhBMP-2. Through further study and development, the application of 3D-printed customized alloplastic grafts will be extended to various fields of bone regeneration.     

Bone Fracture-Treatment Method: Fixing 3D-Printed Polycaprolactone Scaffolds with Hydrogel Type Bone-Derived Extracellular Matrix and β-Tricalcium Phosphate as an Osteogenic Promoter

Bone formation and growth are crucial for treating bone fractures. Improving bone-reconstruction methods using autologous bone and synthetic implants can reduce the recovery time. Here, we investigated three treatments using two different materials, a bone-derived decellularized extracellular matrix (bdECM) and β-tricalcium phosphate (β-TCP), individually and in combination, as osteogenic promoter between bone and 3D-printed polycaprolactone scaffold (6-mm diameter) in rat calvarial defects (8-mm critical diameter). The materials were tested with a human pre-osteoblast cell line (MG63) to determine the effects of the osteogenic promoter on bone formation in vitro. A polycaprolactone (PCL) scaffold with a porous structure was placed at the center of the in vivo rat calvarial defects. The gap between the defective bone and PCL scaffold was filled with each material. Animals were sacrificed four weeks post-implantation, and skull samples were preserved for analysis. The preserved samples were scanned by micro-computed tomography and analyzed histologically to examine the clinical benefits of the materials. The bdECM–β-TCP mixture showed faster bone formation and a lower inflammatory response in the rats. Therefore, our results imply that a bdECM–β-TCP mixture is an ideal osteogenic promoter for treating fractures.     

Biological Response to Bioinspired Microporous 3D-Printed Scaffolds for Bone Tissue Engineering

The scaffold is a key element in the field of tissue engineering, especially when large defects or substitutions of pathological tissues or organs need to be clinically addressed. The expected outcome is strongly dependent on the cell–scaffold interaction and the integration with the surrounding biological tissue. Indeed, mimicking the natural extracellular matrix (ECM) of the tissue to be healed represents a further optimization that can limit a possible morphological mismatch between the scaffold and the tissue itself. For this aim, and referring to bone tissue engineering, polylactic acid (PLA) scaffolds were 3D printed with a microstructure inspired by the trabecular architecture and biologically evaluated by means of human osteosarcoma SAOS-2 cells. The cells were seeded on two types of scaffolds differing for the designed pore size (i.e., 400 and 600 µm), showing the same growth exponential trend found in the control and no significant alterations in the actin distribution. The microporous structure of the two tested samples enhanced the protein adsorption capability and mRNA expression of markers related to protein synthesis, proliferation, and osteoblast differentiation. Our findings demonstrate that 3D-printed scaffolds support the adhesion, growth, and differentiation of osteoblast-like cells and the microporous architecture, mimicking the natural bone hierarchical structure, and favoring greater bioactivity. These bioinspired scaffolds represent an interesting new tool for bone tissue engineering and regenerative medicine applications.     

三维打印珍珠粉-硫酸钙/聚己内酯复合支架及性能研究

具有生物相容性的支架可以作为可控的细胞外环境,供细胞附着、增殖、分化以及组织生成,在组织工程中有着重要的作用。本研究运用三维打印技术制备了珍珠粉-硫酸钙/聚己内酯(Pearl-CaSO_4/PCL)复合支架,详细研究了珍珠粉含量对复合支架的理化性能和生物学性能的影响。结果表明,复合支架具有350mm左右的三维连通大孔,其孔隙率约60%,支架强度可达8 MPa。珍珠粉的复合能够有效调节复合支架的降解速率并稳定支架周围的体液环境。细胞实验结果表明,Pearl-CaSO_4/PCL复合支架能够促进骨髓间充质干细胞的增殖与分化,且与珍珠粉的含量呈正相关。因此,Pearl-CaSO_4/PCL复合支架在骨缺损修复领域具有应用前景。     

Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide–polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.     

Solvent-Cast 3D Printing of Biodegradable Polymer Scaffolds

3D printing is a popular fabrication technique because of its ability to produce complex architectures. Melt-based 3D printing is widely used for thermoplastic polymers like poly(caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA) because of their low processing temperatures. However, traditional melt-based techniques require processing temperatures and pressures high enough to achieve continuous flow, limiting the type of polymer that can be printed. Solvent-cast printing (SCP) offers an alternative approach to print a wider range of polymers. Polymers are dissolved in a volatile solvent that evaporates during deposition to produce a solid polymer filament. SCP, therefore, requires optimizing polymer concentration in the ink, print pressure, and print speed to achieve desired print fidelity. Here, capillary flow analysis shows how print pressure affects the process-apparent viscosity of PCL, PLA, and PLGA inks. Ink viscosity is also measured using rheology, which is used to link a specific ink viscosity to a predicted set of print pressure and print speed for all three polymers. These results demonstrate how this approach can be used to accelerate optimization by significantly reducing the number of parameter combinations. This strategy can be applied to other polymers to expand the library of polymers printable with SCP.     

Enhanced Regeneration of Vascularized Adipose Tissue with Dual 3D-Printed Elastic Polymer/dECM Hydrogel Complex

A flexible and bioactive scaffold for adipose tissue engineering was fabricated and evaluated by dual nozzle three-dimensional printing. A highly elastic poly (L-lactide-co-ε-caprolactone) (PLCL) copolymer, which acted as the main scaffolding, and human adipose tissue derived decellularized extracellular matrix (dECM) hydrogels were used as the printing inks to form the scaffolds. To prepare the three-dimensional (3D) scaffolds, the PLCL co-polymer was printed with a hot melting extruder system while retaining its physical character, similar to adipose tissue, which is beneficial for regeneration. Moreover, to promote adipogenic differentiation and angiogenesis, adipose tissue-derived dECM was used. To optimize the printability of the hydrogel inks, a mixture of collagen type I and dECM hydrogels was used. Furthermore, we examined the adipose tissue formation and angiogenesis of the PLCL/dECM complex scaffold. From in vivo experiments, it was observed that the matured adipose-like tissue structures were abundant, and the number of matured capillaries was remarkably higher in the hydrogel–PLCL group than in the PLCL-only group. Moreover, a higher expression of M2 macrophages, which are known to be involved in the remodeling and regeneration of tissues, was detected in the hydrogel–PLCL group by immunofluorescence analysis. Based on these results, we suggest that our PLCL/dECM fabricated by a dual 3D printing system will be useful for the treatment of large volume fat tissue regeneration.     

Suture Fiber Reinforcement of a 3D Printed Gelatin Scaffold for Its Potential Application in Soft Tissue Engineering

Gelatin has excellent biological properties, but its poor physical properties are a major obstacle to its use as a biomaterial ink. These disadvantages not only worsen the printability of gelatin biomaterial ink, but also reduce the dimensional stability of its 3D scaffolds and limit its application in the tissue engineering field. Herein, biodegradable suture fibers were added into a gelatin biomaterial ink to improve the printability, mechanical strength, and dimensional stability of the 3D printed scaffolds. The suture fiber reinforced gelatin 3D scaffolds were fabricated using the thermo-responsive properties of gelatin under optimized 3D printing conditions (−10 °C cryogenic plate, 40–80 kPa pneumatic pressure, and 9 mm/s printing speed), and were crosslinked using EDC/NHS to maintain their 3D structures. Scanning electron microscopy images revealed that the morphologies of the 3D printed scaffolds maintained their 3D structure after crosslinking. The addition of 0.5% (w/v) of suture fibers increased the printing accuracy of the 3D printed scaffolds to 97%. The suture fibers also increased the mechanical strength of the 3D printed scaffolds by up to 6-fold, and the degradation rate could be controlled by the suture fiber content. In in vitro cell studies, DNA assay results showed that human dermal fibroblasts’ proliferation rate of a 3D printed scaffold containing 0.5% suture fiber was 10% higher than that of a 3D printed scaffold without suture fibers after 14 days of culture. Interestingly, the supplement of suture fibers into gelatin biomaterial ink was able to minimize the cell-mediated contraction of the cell cultured 3D scaffolds over the cell culture period. These results show that advanced biomaterial inks can be developed by supplementing biodegradable fibers to improve the poor physical properties of natural polymer-based biomaterial inks.     

Cryogenic 3D Printing of w/o Pickering Emulsions Containing Bifunctional Drugs for Producing Hierarchically Porous Bone Tissue Engineering Scaffolds with Antibacterial Capability

How to fabricate bone tissue engineering scaffolds with excellent antibacterial and bone regeneration ability has attracted increasing attention. Herein, we produced a hierarchical porous β-tricalcium phosphate (β-TCP)/poly(lactic-co-glycolic acid)-polycaprolactone composite bone tissue engineering scaffold containing tetracycline hydrochloride (TCH) through a micro-extrusion-based cryogenic 3D printing of Pickering emulsion inks, in which the hydrophobic silica (h-SiO₂) nanoparticles were used as emulsifiers to stabilize composite Pickering emulsion inks. Hierarchically porous scaffolds with desirable antibacterial properties and bone-forming ability were obtained. Grid scaffolds with a macroscopic pore size of 250.03 ± 75.88 μm and a large number of secondary micropores with a diameter of 24.70 ± 15.56 μm can be fabricated through cryogenic 3D printing, followed by freeze-drying treatment, whereas the grid structure of scaffolds printed or dried at room temperature was discontinuous, and fewer micropores could be observed on the strut surface. Moreover, the impartment of β-TCP in scaffolds changed the shape and density of the micropores but endowed the scaffold with better osteoconductivity. Scaffolds loaded with TCH had excellent antibacterial properties and could effectively promote the adhesion, expansion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells afterward. The scaffolds loaded with TCH could realize the strategy to “kill bacteria first, then induce osteogenesis”. Such hierarchically porous scaffolds with abundant micropores, excellent antibacterial property, and improved bone-forming ability display great prospects in treating bone defects with infection.     

Microporosities in 3D-Printed Tricalcium-Phosphate-Based Bone Substitutes Enhance Osteoconduction and Affect Osteoclastic Resorption

Additive manufacturing is a key technology required to realize the production of a personalized bone substitute that exactly meets a patient’s need and fills a patient-specific bone defect. Additive manufacturing can optimize the inner architecture of the scaffold for osteoconduction, allowing fast and reliable defect bridging by promoting rapid growth of new bone tissue into the scaffold. The role of scaffold microporosity/nanoarchitecture in osteoconduction remains elusive. To elucidate this relationship, we produced lithography-based osteoconductive scaffolds from tricalcium phosphate (TCP) with identical macro- and microarchitecture, but varied their nanoarchitecture/microporosity by ranging maximum sintering temperatures from 1000 °C to 1200 °C. After characterization of the different scaffolds’ microporosity, compression strength, and nanoarchitecture, we performed in vivo studies that showed that ingrowth of bone as an indicator of osteoconduction significantly decreased with decreasing microporosity. Moreover, at the 1200 °C peak sinter temperature and lowest microporosity, osteoclastic degradation of the material was inhibited. Thus, even for wide-open porous TCP-based scaffolds, a high degree of microporosity appears to be essential for optimal osteoconduction and creeping substitution, which can prevent non-unions, the major complication during bone regeneration procedures.