Biocompatibility and osteogenic capacity of additively manufactured biodegradable porous WE43 scaffolds: An in vivo study in a canine model.

Magnesium is the most promising absorbable metallic implant material for bone regeneration and alloy WE43 is already FDA approved for cardiovascular applications. This study investigates the cyto- and biocompatibility of novel additively manufactured (AM) porous WE43 scaffolds as well as their osteogenic potential and degradation characteristics in an orthotopic canine bone defect model. The cytocompatibility was demonstrated using modified ISO 10993-conform extract-based indirect and direct assays, respectively. Additionally, degradation rates of WE43 scaffolds were quantified in vitro prior to absorption tests in vivo. Complete blood cell counts, blood biomarker analyses, blood trace element analyses as well as multi-organ histopathology demonstrated excellent biocompatibility of porous y WE43 scaffolds for bone defect repair. Micro-CT analyses further showed a relatively higher absorption rate during the initial four weeks upon implantation (i.e., 36 % ± 19 %) than between four and 12 weeks (41 % ± 14 %), respectively. Of note, the porous WE43 implants were surrounded by newly formed bony tissue as early as four weeks after implantation when unmineralized trabecular ingrowth was detected. After 12 weeks, a substantial amount of mineralized bone was detected inside and around the gradually disappearing implants. This first study on AM porous WE43 implants in canine bone defects demonstrates the potential of this alloy for in vivo applications in humans. Our data further underscore the need to control initial bulk absorption kinetics through surface modifications.

Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects.

Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction. Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly ( ε -caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses. Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group. Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.

Micro-Computed Tomography Analysis and Histological Observation of the Screw-Bone Interface of Novel Porous Scaffold Core Pedicle Screws and Hollow Lateral Hole Pedicle Screws: A Comparative Study in Bama Pigs.

OBJECTIVE: Screw loosening is a common complication of pedicle screw internal fixation surgery. This study aimed to investigate whether the application of a porous scaffold structure can increase the contact area between screws and bone tissue by comparing the bone ingrowth and screw-bone interface of porous scaffold core pedicle screws (PSCPSs) and hollow lateral hole pedicle screws (HLHPSs) in the lumbar spine of Bama pigs. METHODS: Sixteen pedicle screws of both types were implanted into the bilateral pedicles of the L1-4 vertebrae of 2 Bama pigs. All Bama pigs were sacrificed and the lumbar spine was freed into individual vertebrae at 16 weeks postoperatively. After the vertebrae were made into screw-centered specimens, micro-computed tomography analysis and histological observation were performed to assess the screw-bone interface and bone growth around and within the screws. RESULTS: We found that the bone condition around PSCPSs and HLHPSs did not show significant differences on micro-computed tomography three-dimensional reconstruction images. CT transverse views showed different bone growth inside the 2 screws. In PSCPSs, bone tissue was seen to fill the internal pores and was evenly distributed around each strut. Inside HLHPSs, bone growth was confined to 1 side of the screw and did not fill the entire cavity. Osteometric analysis showed that bone volume fraction and trabecular number, the parameters representing bone mass, were higher in PSCPSs than in HLHPSs. These differences were not statistically significant (P > 0.05). Histological observations visualized that the osseointegration within PSCPSs was superior to that of HLHPSs, and the tight integration of bone tissue with the porous scaffold resulted in a larger screw-bone integration area in PSCPSs than in HLHPSs. CONCLUSIONS: Compared with HLHPSs, PSCPSs possessing a porous scaffold core could promote bone ingrowth and osseointegration, resulting in an effective enhancement of the combined area of the screw-bone interface.

[Design and performance study of bone trabecular scaffolds based on triply periodic minimal surface method].

Triply periodic minimal surface (TPMS) is widely used because it can be used to control the shape of porous scaffolds precisely by formula. In this paper, an I-wrapped package (I-WP) type porous scaffolds were constructed. The finite element method was used to study the relationship between the wall thickness and period, the morphology and mechanical properties of the scaffolds, as well as to study the compression and fluid properties. It was found that the porosity of I-WP type scaffolds with different wall thicknesses (0.1 ~ 0.2 mm) and periods (I-WP 1 ~ I-WP 5) ranged from 68.01% ~ 96.48%, and the equivalent elastic modulus ranged from 0.655 ~ 18.602 GPa; the stress distribution of the scaffolds tended to be uniform with the increase of periods and wall thicknesses; the equivalent elastic modulus of the I-WP type scaffolds was basically unchanged after the topology optimization, and the permeability was improved by 52.3%. In conclusion, for the I-WP type scaffolds, the period parameter can be adjusted first, then the wall thickness parameter can be controlled. Topology optimization can be combined to meet the design requirements. The I-WP scaffolds constructed in this paper have good mechanical properties and meet the requirements of repairing human bone tissue, which may provide a new choice for the design of artificial bone trabecular scaffolds.

Biomechanical Properties of Novel Porous Scaffold Core and Hollow Lateral Hole Pedicle Screws: A Comparative Study in Bama Pigs.

OBJECTIVE: Screw loosening is a common complication of internal fixation of pedicle screw. Therefore, the development of a pedicle screw with low loosening rate and high biosafety is of great clinical significance. This study aimed to investigate whether the application of a porous scaffold structure can improve the stability of pedicle screws by comparing the biomechanical properties of novel porous scaffold core pedicle screws (PSCPSs) with those of hollow lateral hole pedicle screws (HLHPSs) in a porcine lumbar spine. METHODS: Thirty-two pedicle screws of both types were implanted bilaterally into the L1-4 vertebrae of four Bama pigs, with our newly designed PSCPSs on the right and HLHPSs on the left. All the Bama pigs were sacrificed 16 weeks postoperatively, and the lumbar spine was freed into individual vertebrae. Biomechanical properties of both the pedicle screws were evaluated using pull-out tests, as well as cyclic bending and pull-out tests, while the mechanical properties were assessed using three-point bending tests. The data generated were statistically analyzed using paired-sample t-tests and two independent sample t-tests. RESULTS: We found that the maximal pull-out forces before and after cyclic bending of the PSCPSs (1161.50 ± 337.98 N and 1075.25 ± 223.33 N) were significantly higher than those of the HLHPSs (948.38 ± 194.32 N and 807.13 ± 242.75 N) (p < 0.05, p < 0.05). In 800 cycles of the bending tests, neither PSCPS nor HLHPS showed loosening or visible detachment, but their maximal pull-out forces after cyclic bending tests decreased compared to those in cycles without cyclic bending tests (7.43% and 14.89%, respectively), with no statistical significance (p > 0.05 and p > 0.05, respectively). Additionally, both screws buckled rather than broke in the three-point bending tests, with no statistically significant differences between the maximal bending load and modulus of elasticity of the two screws (p > 0.05 and p > 0.05, respectively). CONCLUSIONS: Compared with the HLHPSs, the PSCPSs have greater pull-out resistance and better fatigue tolerance with appropriate mechanical properties. Therefore, PSCPSs theoretically have significant potential for clinical applications in reducing the incidence of loosening after pedicle screw implantation.

Impacts of permeability and effective diffusivity of porous scaffolds on bone ingrowth: In silico and in vivo analyses.

The permeability and the effective diffusivity of a porous scaffold are critical in the bone-ingrowth process. However, design guidelines for porous structures are still lacking due to inadequate understanding of the complex physiological processes involved. In this study, a model integrating the fundamental biological processes of bone regeneration was constructed to investigate the roles of permeability and effective diffusivity in regulating bone deposition in scaffolds. The in silico analysis results were confirmed in vivo by examining bone depositions in three diamond lattice scaffolds manufactured using selective laser melting. The findings show that the scaffolds with better permeability and effective diffusivity had deeper bone ingrowth and greater bone volume. Compared to permeability, effective diffusivity exhibited greater sensitivity to the orientation of porous structures, and bone ingrowth was deeper in the directions with higher effective diffusivity in spite of identical pore size. A 4.8-fold increase in permeability and a 1.6-fold increase in effective diffusivity by changing the porous structure led to a 1.5-fold increase in newly formed bone. The effective diffusivity of the porous scaffold affects the distribution of osteogenic growth factor, which in turn impacts cell migration and bone deposition through chemotaxis effects. Therefore, effective diffusivity may be a more suitable indicator for porous scaffolds because our study shows changes in this parameter determine changes in bone distribution and bone volume.

Bio-functional hydroxyapatite-coated 3D porous polyetherketoneketone scaffold for enhanced osteogenesis and osteointegration in orthopedic applications.

Polyetherketoneketone (PEKK), a high-performance thermoplastic special engineering material, maintains bone-like mechanical properties and has received considerable attention in the biomedical field. The 3D printing technique enables the production of porous scaffolds with a honeycomb structure featuring precisely controlled pore size, porosity and interconnectivity, which holds significant potential for applications in tissue engineering. The ideal pore architecture of porous PEKK scaffolds has yet to be elucidated. Porous PEKK scaffolds with five pore sizes P200 (225 ± 9.8 µm), P400 (411 ± 22.1 µm), P600 (596 ± 23.4 µm), P800 (786 ± 24.2 µm) and P1000 (993 ± 26.0 µm) were produced by a 3D printer. Subsequently, the optimum pore size, the P600, for mechanical properties and osteogenesis was selected based on in vitro experiments. To improve the interfacial bioactivity of porous PEKK scaffolds, hydroxyapatite (HAp) crystals were generated via in situ biomimetic mineralization induced by the phase-transited lysozyme coating. Herein, a micro/nanostructured surface showing HAp crystals on PEKK scaffold was developed. In vitro and in vivo experiments confirmed that the porous PEKK-HAp scaffolds exhibited highly interconnected pores and functional surface structures that were favorable for biocompatibility and osteoinductivity, which boosted bone regeneration. Therefore, this work not only demonstrates that the pore structure of the P600 scaffold is suitable for PEKK orthopedic implants but also sheds light on a synergistic approach involving 3D printing and biomimetic mineralization, which has the potential to yield customized 3D PEKK-HAp scaffolds with enhanced osteoinductivity and osteogenesis, offering a promising strategy for bone tissue engineering.

Developing Porous Fibrin Scaffolds with Tunable Anisotropic Features to Direct Myoblast Orientation.

Functional regeneration of anisotropically aligned tissues such as ligaments, microvascular networks, myocardium, or skeletal muscle requires a temporal and spatial series of biochemical and biophysical cues to direct cell functions that promote native tissue regeneration. When these cues are lost during traumatic injuries such as volumetric muscle loss (VML), scar formation occurs, limiting the regenerative capacity of the tissue. Currently, autologous tissue transfer is the gold standard for treating injuries such as VML but can result in adverse outcomes including graft failure, donor site morbidity, and excessive scarring. Tissue-engineered scaffolds composed of biomaterials, cells, or both have been investigated to promote functional tissue regeneration but are still limited by inadequate tissue ingrowth. These scaffolds should provide precisely tuned topographies and stiffnesses using proregenerative materials to encourage tissue-specific functions such as myoblast orientation, followed by aligned myotube formation and recovery of functional contraction. In this study, we describe the design and characterization of novel porous fibrin scaffolds with anisotropic microarchitectural features that recapitulate the native tissue microenvironment and offer a promising approach for regeneration of aligned tissues. We used directional freeze-casting with varied fibrin concentrations and freezing temperatures to produce scaffolds with tunable degrees of anisotropy and strut widths. Nanoindentation analyses showed that the moduli of our fibrin scaffolds varied as a function of fibrin concentration and were consistent with native skeletal muscle tissue. Quantitative morphometric analyses of myoblast cytoskeletons on scaffold microarchitectures demonstrated enhanced cell alignment as a function of microarchitectural morphology. The ability to precisely control the anisotropic features of fibrin scaffolds promises to provide a powerful tool for directing aligned tissue ingrowth and enhance functional regeneration of tissues such as skeletal muscle.

Generation of Pearl/Calcium Phosphate Composite Particles and Their Integration into Porous Chitosan Scaffolds for Bone Regeneration.

Bone tissue engineering using osteoconductive scaffolds holds promise for regeneration, with pearl powder gaining interest for its bioactive qualities. This study used freeze drying to create chitosan (CS) scaffolds with pearl/calcium phosphate (p/CaP) powders, mimicking bone tissue structurally and compositionally. Characterization included scanning electron microscopy (SEM) and mechanical testing. X-ray diffraction (XRD) Fourier-transform infrared-photoacoustic photo-acoustic sampling (FTIR-PAS), and FTIR- attenuated total reflectance (FTIR-ATR) were used to characterize p/CaP. In vitro tests covered degradation, cell activity, and SEM analysis. The scaffolds showed notable compressive strength and modulus enhancements with increasing p/CaP content. Porosity, ranging from 60% to 90%, decreased significantly at higher pearl/CaP ratios. Optimal cell proliferation and differentiation were observed with scaffolds containing up to 30 wt.% p/CaP, with 30 wt.% pearl powder and 30 wt.% p/CaP yielding the best results. In conclusion, pearl/calcium phosphate chitosan (p/CaP_CS) composite scaffolds emerged as promising biomaterials for bone tissue engineering, combining structural mimicry and favourable biological responses.

A Photochemically Active Cu2O Nanoparticle Endows Scaffolds with Good Antibacterial Performance by Efficiently Generating Reactive Oxygen Species.

Cuprous oxide (Cu2O) has great potential in photodynamic therapy for implant-associated infections due to its good biocompatibility and photoelectric properties. Nevertheless, the rapid recombination of electrons and holes weakens its photodynamic antibacterial effect. In this work, a new nanosystem (Cu2O@rGO) with excellent photodynamic performance was designed via the in situ growth of Cu2O on reduced graphene oxide (rGO). Specifically, rGO with lower Fermi levels served as an electron trap to capture photoexcited electrons from Cu2O, thereby promoting electron-hole separation. More importantly, the surface of rGO could quickly transfer electrons from Cu2O owing to its excellent conductivity, thus efficiently suppressing the recombination of electron-hole pairs. Subsequently, the Cu2O@rGO nanoparticle was introduced into poly-L-lactic acid (PLLA) powder to prepare PLLA/Cu2O@rGO porous scaffolds through selective laser sintering. Photochemical analysis showed that the photocurrent of Cu2O@rGO increased by about two times after the incorporation of GO nanosheets, thus enhancing the efficiency of photogenerated charge carriers and promoting electron-hole separation. Moreover, the ROS production of the PLLA/Cu2O@rGO scaffold was significantly increased by about two times as compared with that of the PLLA/Cu2O scaffold. The antibacterial results showed that PLLA/Cu2O@rGO possessed antibacterial rates of 83.7% and 81.3% against Escherichia coli and Staphylococcus aureus, respectively. In summary, this work provides an effective strategy for combating implant-related infections.

Cell-free chitosan/silk fibroin/bioactive glass scaffolds with radial pore for in situ inductive regeneration of critical-size bone defects.

Tissue-engineered is an effective method for repairing critical-size bone defects. The application of bioactive scaffold provides artificial matrix and suitable microenvironment for cell recruitment and extracellular matrix deposition, which can effectively accelerate the process of tissue regeneration. Among various scaffold properties, appropriate pore structure and distribution have been proven to play a crucial role in inducing cell infiltration differentiation and in-situ tissue regeneration. In this study, a chitosan (CS) /silk fibroin (SF) /bioactive glass (BG) composite scaffold with distinctive radially oriented pore structure was constructed. The composite scaffolds had stable physical and chemical properties, a unique pore structure of radial arrangement from the center to the periphery and excellent mechanical properties. In vitro biological studies indicated that the CS/SF/BG scaffold could promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the expression of related genes due to the wide range of connected pore structures and released active elements. Furthermore, in vivo study showed CS/SF/BG scaffold with radial pores was more conducive to the repair of skull defects in rats with accelerated healing speed during the bone tissue remodeling process. These results demonstrated the developed CS/SF/BG scaffold would be a promising therapeutic strategy for the repair of bone defects regeneration.

Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration.

The essential role of the neural network in enhancing bone regeneration has often been overlooked in biomaterial design, leading to delayed or compromised bone healing. Engineered mesenchymal stem cells (MSCs)-derived exosomes are becoming increasingly recognized as potent cell-free agents for manipulating cellular behavior and improving therapeutic effectiveness. Herein, MSCs are stimulated with nerve growth factor (NGF) to regulate exosomal cargoes to improve neuro-promotive potential and facilitate innervated bone regeneration. In vitro cell experiments showed that the NGF-stimulated MSCs-derived exosomes (N-Exos) obviously improved the cellular function and neurotrophic effects of the neural cells, and consequently, the osteogenic potential of the osteo-reparative cells. Bioinformatic analysis by miRNA sequencing and pathway enrichment revealed that the beneficial effects of N-Exos may partly be ascribed to the NGF-elicited multicomponent exosomal miRNAs and the subsequent regulation and activation of the MAPK and PI3K-Akt signaling pathways. On this basis, N-Exos were delivered on the micropores of the 3D-printed hierarchical porous scaffold to accomplish the sustained release profile and extended bioavailability. In a rat model with a distal femoral defect, the N-Exos-functionalized hierarchical porous scaffold significantly induced neurovascular structure formation and innervated bone regeneration. This study provided a feasible strategy to modulate the functional cargoes of MSCs-derived exosomes to acquire desirable neuro-promotive and osteogenic potential. Furthermore, the developed N-Exos-functionalized hierarchical porous scaffold may represent a promising neurovascular-promotive bone reparative scaffold for clinical translation.

Evaluation of Porous (Poly(lactide-co-glycolide)-co-(ε-caprolactone)) Polyurethane for Use in Orthopedic Scaffolds.

To develop an orthopedic scaffold that could overcome the limitations of implants used in clinics, we designed poly(ester-urethane) foams and compared their properties with those of a commercial gold standard. A degradable poly(ester-urethane) was synthetized by polyaddition between a diisocyanate poly(ε-caprolactone) prepolymer (PCL di-NCO, Mn = 2400 g·mol-1) and poly(lactic-co-glycolic acid) diol (PLGA, Mn = 2200 g·mol-1) acting as a chain extender. The resulting high-molecular-weight poly(ester-urethane) (PEU, Mn = 87,000 g·mol-1) was obtained and thoroughly characterized by NMR, FTIR and SEC-MALS. The porous scaffolds were then processed using the solvent casting (SC)/particle leaching (PL) method with different NaCl crystal concentrations. The morphology, pore size and porosity of the foams were evaluated using SEM, showing interconnected pores with a uniform size of around 150 µm. The mechanical properties of the scaffolds are close to those of the human meniscus (Ey = 0.5~1 MPa). Their degradation under accelerated conditions confirms that incorporating PLGA into the scaffolds greatly accelerates their degradation rate compared to the gold-standard implant. Finally, a cytotoxicity study confirmed the absence of the cytotoxicity of the PEU, with a 90% viability of the L929 cells. These results suggest that degradable porous PLGA/PCL poly(ester-urethane) has potential in the development of meniscal implants.

Gaussian random field-based characterization and reconstruction of cancellous bone microstructure considering the constraint of correlation structure.

The macro scale physical properties of cancellous bone materials are governed by the microstructural features, which is of great significance for the multi-scale research of cancellous bone and the inverse design of bone-mimicking materials. Therefore, it is essential to characterize the natural cancellous bone samples, and reconstruct the microstructures with the biomimetic osteointegration and mechanical properties. In this research, a novel approach for the characterization and reconstruction of cancellous bone was proposed, based on the medical image analysis and anisotropic three-dimensional Gaussian random field (GRF). The geometric similarity, i.e. the interface curvature distribution (ISD), was meticulously studied, which is important to the osteointegration ability. And the mechanical properties were validated by the stress-strain curves under the large compressive strain simulated by the smoothed particle hydrodynamic (SPH) method. In addition, the effects of the generation parameters of GRF-based biomimetic microstructures on the apparent properties were analyzed. The ISD results demonstrated that both GRF and micro-CT groups had the similar columnar morphological properties, while the latter had more hyperbolic features. And it was found that the GRF-based biomimetic microstructures and the natural bone samples based on micro-CT (MCT) had the similar failure mode. The concordance correlation coefficient between MCT and GRF pairs was 0.8685, with a Pearson ρ value of 0.8804, and significance level p<0.0001. The Bland-Altman LoA was 0.1647 MPa with 95 % (1.96SD) lower and upper bound value between -0.2892 and 0.6185 MPa. The two groups had almost the same elastic modulus with the mean absolute percentage error (MAPE) of 7.84 %. While the yield stress and total conversion energy of the GRF-based samples were lower than those of the natural bone samples, and the MAPE were 16.99 % and 16.27 %, respectively. Although it meant the lower structural efficiency, the huge design space of this approach and advanced 3D printing technology can provide great potential for the design of orthopedic implants.

Investigation of cell infiltration and colonization in 3D porous scaffolds via integrated experimental and computational strategies.

This study aimed to integrate experimental and computational methods to systematically investigate cell infiltration and colonization within porous scaffolds. Poly(lactic acid) discs (Diameter: 6 mm; Thickness: 500 µm) with open pores (Diameter: 400-1100 µm), corners (Angle: 30-120°) and gaps (Distance: 100-500 µm), and cellulosic scaffolds with irregular pores (Diameter: 50-300 µm) were situated in tissue culture plates and cultured with human dermal fibroblasts (HDFs). Both phase contrast and scanning electron microscopy revealed that HDFs initially proliferated on scaffold surfaces, then infiltrated into the porous structures via cell bridging and stacking strategies, which was affected by the initial cell seeding densities, porous structures and culture times. Based on the density-dependent cell growths in two-dimensional cell cultures, power law models were developed to quantitatively simulate cell growths on scaffold surfaces. Model analysis predicted the effect of cell seeding efficiency on cell infiltrations into the porous scaffolds, which was further validated via series cell seeding experiments. The novelty of this research lies in the incorporation of multiple experimental and computational strategies, which enables the mechanistic insights of cell invasion and colonization in porous scaffolds, also facilitates the development of suitable bioprocesses for cell seeding and tissue manufacturing in Tissue Engineering and Regenerative Medicine.

Bamboo-Inspired Porous Scaffolds for Advanced Orthopedic Implants: Design, Mechanical Properties, and Fluid Characteristics.

In orthopedic implant development, incorporating a porous structure into implants can reduce the elastic modulus to prevent stress shielding but may compromise yield strength, risking prosthesis fracture. Bamboo's natural structure, with its exceptional strength-to-weight ratio, serves as inspiration. This study explores biomimicry using bamboo-inspired porous scaffolds (BISs) resembling cortical bone, assessing their mechanical properties and fluid characteristics. The BIS consists of two 2D units controlled by structural parameters α and ß. The mechanical properties, failure mechanisms, energy absorption, and predictive performance are investigated. BIS exhibits mechanical properties equivalent to those of natural bone. Specifically, α at 4/3 and ß at 2/3 yield superior mechanical properties, and the destruction mechanism occurs layer by layer. Besides, the Gibson-Ashby models with different parameters are established to predict mechanical properties. Fluid dynamics analysis reveals two high-flow channels in BISs, enhancing nutrient delivery through high-flow channels and promoting cell adhesion and proliferation in low-flow regions. For wall shear stress below 30 mPa (ideal for cell growth), α at 4/3 achieves the highest percentage (99.04%), and ß at 2/3 achieves 98.46%. Permeability in all structural parameters surpasses that of human bone. Enhanced performance of orthopedic implants through a bionic approach that enables the creation of pore structures suitable for implants.

In vitro and in vivo studies on biodegradable Zn porous scaffolds with a drug-loaded coating for the treatment of infected bone defect.

Additively manufactured biodegradable zinc (Zn) scaffolds have great potential to repair infected bone defects due to their osteogenic and antibacterial properties. However, the enhancement of antibacterial properties depends on a high concentration of dissolved Zn2+, which in return deteriorates osteogenic activity. In this study, a vancomycin (Van)-loaded polydopamine (PDA) coating was prepared on pure Zn porous scaffolds to solve the above dilemma. Compared with pure Zn scaffolds according to comprehensive in vitro tests, the PDA coating resulted in a slow degradation and inhibited the excessive release of Zn2+ at the early stage, thus improving cytocompatibility and osteogenic activity. Meanwhile, the addition of Van drug substantially suppressed the attachment and proliferation of S. aureus and E. coli bacterial. Furthermore, in vivo implantation confirmed the simultaneously improved osteogenic and antibacterial functions by using the pure Zn scaffolds with Van-loaded PDA coating. Therefore, it is promising to employ biodegradable Zn porous scaffolds with the proposed drug-loaded coating for the treatment of infected bone defects.

Ascorbic Acid 2-Phosphate Releasing Supercritically Foamed Porous Poly-L-Lactide-Co-ε-Caprolactone Scaffold Enhances the Collagen Production of Human Vaginal Stromal Cells: A New Approach for Vaginal Tissue Engineering.

BACKGROUND: The reconstructive surgery of vaginal defects is highly demanding and susceptible to complications, especially in larger defects requiring nonvaginal tissue grafts. Thus, tissue engineering-based solutions could provide a potential approach to the reconstruction of vaginal defects. METHODS: Here, we evaluated a novel porous ascorbic acid 2-phosphate (A2P)-releasing supercritical carbon dioxide foamed poly-L-lactide-co-ε-caprolactone (scPLCLA2P) scaffold for vaginal reconstruction with vaginal epithelial (EC) and stromal (SC) cells. The viability, proliferation, and phenotype of ECs and SCs were evaluated in monocultures and in cocultures on d 1, d 7 and d 14. Furthermore, the collagen production of SCs on scPLCLA2P was compared to that on scPLCL without A2P on d 14. RESULTS: Both ECs and SCs maintained their viability on the scPLCLA2P scaffold in mono- and coculture conditions, and the cells maintained their typical morphology during the 14-d culture period. Most importantly, the scPLCLA2P scaffolds supported the collagen production of SCs superior to plain scPLCL based on total collagen amount, collagen I and III gene expression results and collagen immunostaining results. CONCLUSION: This is the first study evaluating the effect of A2P on vaginal tissue engineering, and the results are highly encouraging, indicating that scPLCLA2P has potential as a scaffold for vaginal tissue engineering.

Model-Based Design to Enhance Neotissue Formation in Additively Manufactured Calcium-Phosphate-Based Scaffolds.

In biomaterial-based bone tissue engineering, optimizing scaffold structure and composition remains an active field of research. Additive manufacturing has enabled the production of custom designs in a variety of materials. This study aims to improve the design of calcium-phosphate-based additively manufactured scaffolds, the material of choice in oral bone regeneration, by using a combination of in silico and in vitro tools. Computer models are increasingly used to assist in design optimization by providing a rational way of merging different requirements into a single design. The starting point for this study was an in-house developed in silico model describing the in vitro formation of neotissue, i.e., cells and the extracellular matrix they produced. The level set method was applied to simulate the interface between the neotissue and the void space inside the scaffold pores. In order to calibrate the model, a custom disk-shaped scaffold was produced with prismatic canals of different geometries (circle, hexagon, square, triangle) and inner diameters (0.5 mm, 0.7 mm, 1 mm, 2 mm). The disks were produced with three biomaterials (hydroxyapatite, tricalcium phosphate, and a blend of both). After seeding with skeletal progenitor cells and a cell culture for up to 21 days, the extent of neotissue growth in the disks' canals was analyzed using fluorescence microscopy. The results clearly demonstrated that in the presence of calcium-phosphate-based materials, the curvature-based growth principle was maintained. Bayesian optimization was used to determine the model parameters for the different biomaterials used. Subsequently, the calibrated model was used to predict neotissue growth in a 3D gyroid structure. The predicted results were in line with the experimentally obtained ones, demonstrating the potential of the calibrated model to be used as a tool in the design and optimization of 3D-printed calcium-phosphate-based biomaterials for bone regeneration.

Optimal mechanical properties of Hydroxyapatite gradient Voronoi porous scaffolds for bone applications - A numerical study.

Irregular Voronoi-based lattice (IVL) structures in tissue engineering (TE) have significant potential for bone regeneration. These scaffolds can mimic natural human bone interconnectivity by gradually altering strut thickness (ST) and seed point space (PS), which affects both mechanical and biological characteristics. This paper investigates the impact of design parameters, ST and PS, on Hydroxyapatite (HA) ILV structures' mechanical properties (elastic modulus (E) and maximum compressive strength (MCS)) and geometrical characteristics (pore number, size, and distribution, surface area (SA), and surface area-to-volume ratio (SA/VR)). Four types of IVL scaffolds were designed; PC-TC (Constant PS-Constant ST), PC-TG (Constant PS-Gradient ST), PG-TC (Gradient PS-Constant ST), and PG-TG (Gradient PS-Gradient ST). The study, conducted through linear static structural finite element analysis (FEA) with maximum stress criteria, underscores the profound impact of irregularity and morphology on mechanical performance and geometrical features. Regarding SA and SA/VR, a comparison between PC-TC with other proposed scaffolds showed a minor improvement for PC-TG, while higher significant improvements were found for both PG-TG and PG-TC. In terms of pores distribution and number, no noticeable improvement was observed for the PC-TG scaffold compared to PC-TC. In contrast, PG-TC and PG-TG lattices demonstrated a variety of pore distributions and approximately doubled pore numbers. Studying mechanical properties, considering E and MCS, showcases substantial gains for PG-TC. It, however, revealed that for the rest of the scaffolds, no enhancement was observed regarding E. Based on these results, gradient PS proved to be more effective than gradient ST in enhancing mechanical performance and geometrical properties. Due to these improvements, this study holds promise for expediting bone regeneration and reducing postoperative complications in bone replacement applications.