Scaffolds For Bone Regeneration Research Articles

Development of a multi-functional naringin-loaded bioglass/carboxymethyl chitosan/silk fibroin porous scaffold for hemostasis and critical size bone regeneration.

Persistent bleeding and limited repair capacity greatly threaten patients with bone destruction. Designing inorganic-organic biomimetic scaffolds with quick hemostasis and osteogenesis functions will solve this problem. A novel degradable and naringin (NG) loaded porous scaffold (SCB-N) based on APTES-modified bioactive glass (ABG), carboxymethyl chitosan and silk fibroin is developed. ABG and NG enhance the strength of the scaffolds. The scaffolds can release NG and bioactive ions (Ca2+ and Si4+), promoting the expression of osteogenesis (OCN, BMP-2), angiogenesis (VEGF), and neurogenesis (TB3, GFAP) genes in bone mesenchymal stem cells (BMSCs) and the related proteins (OCN, BMP-2, VEGF, GFAP). When implanting the scaffolds in rat cranial critical size defects, all scaffolds exhibit good compatibility, and SCB-N2 (with ABG and 1mg/mL NG) group significantly promotes new bone regeneration and the formation of M2-type macrophages. Transcriptome sequencing results confirmed the osteogenic differentiation of BMSCs stimulated by SCB-N2 scaffolds is mainly regulated through MAPK and Wnt signaling pathways. Moreover, SCB-N2 group demonstrates quick hemostasis in vitro and in vivo due to the high adsorption ability and Ca ions release. The novel bionic scaffolds loaded with ion/traditional Chinese medicine monomer, possess the capabilities of hemostasis, neurovascularization, osteogenesis and immunomodulation, therefore exhibiting potential in bone repair.

Tailoring and characterization of bioactive graft material for alveolar bone preservation and regeneration in fresh extraction sockets of dog model

The objective of this study was to tailor an osteoinductive scaffold for alveolar bone regeneration and around immediately placed implants in extraction sockets of dogs. Tailored amorphous multiporous bioactive glass (TAMP -BG) was prepared and characterized for bioactivity and response of human alveolar bone marrow mesenchymal stem cells (hABMSCs). Extraction sockets of twenty-two male mongrel dogs received TAMP-BG in the right side around implant in the distal socket of the mandibular fourth premolar (P4), while the adjacent empty mesial socket of the same tooth was filled with the same graft. Autologous bone chips were used in the left side. Animals were euthanized at 1, 2, 4, 8 &12 weeks for histological and SEM analyses. SEM/EDX, FTIR and XRD analyses displayed formation of a bioactive hydroxycarbonated apatite layer. TAMP-BG significantly increased proliferation and migration of hABMSCs. Histologically, at the 1st week, advanced bone healing was shown in TAMP-BG group. At four weeks bone density was significantly higher forTAMP-BG (92.71% ± 1.71) versus control (62.92% ± 2.02) (P = 0.0001).At eight weeks, significant increase in width of buccal plate and height of lingual bony plate was observedfor TAMP-BG grafted implant.The socket orifice width significantly decreased for autologous bone from 1 to 12 weeks (P < 0.001), while it significantly increased for TAMP-BG (P = 0.03). We conclude that TAMP-BG can provide a preservative dynamic microenvironment following extraction up to three months which can be attributed to its unique physico-chemical characteristics.

3D-Printed Gallium-Infused Scaffolds for Osteolysis Intervention and Bone Regeneration

3D-Printed Gallium-Infused Scaffolds for Osteolysis Intervention and Bone Regeneration

3D printed magnetoactive nanocomposite scaffolds for bone regeneration

Simulating the natural cellular environment using magnetic stimuli could be a potential strategy to promote bone tissue regeneration. This study unveiled a novel 3D printed composite scaffold containing polycaprolactone (PCL) and cobalt ferrite/forsterite core-shell nanoparticles (CFF-NPs) to investigate physical, mechanical and biological properties of magnetoactive scaffold under static magnetic field. For this purpose, core-shell structure is synthesized through a two-step synthesis strategy in which cobalt ferrite nanoparticles are prepared via sol-gel combustion method and then are coated through sol-gel method with forsterite. The characterization regarding CFF-NPs reveals that Mg2SiO4-coated CoFe2O4nanoparticles is successfully synthesized with a core-shell structure. Afterwards, CFF-NPs are embedded within the PCL with different percentages, ultimately 3D printed scaffolds were fabricated. Thein vitroassessments demonstrated that the incorporated CFF-NPs are able to cause a decrease in contact angle which was responsible for modulating purposefully the degradation rate of PCL scaffold, resulting in providing the obligatory environment for bone growth. In addition, it was observed that scaffolds including PCL combined with CFF-NPs are susceptible to improve the mechanical performance of nanocomposite scaffolds, up to a certain concentration (50% CFF-NPs and 50% PCL) with compressive modulus of 42.5 MPa. Moreover, when being exposed to simulated body fluid (SBF) solution, hydroxyapatite deposition on the surface of scaffolds was observed. Thus, these compositions may be useful for improving the osteointegration between the implant and bone tissue after implantation. Finally, the simultaneous effect of magnetic nanoparticles and magnetic field of 125 mT evaluated on cellular behavior of scaffolds. The results showed that the cell viability of all groups under magnetic field were better than that for standard condition. Likewise, SEM images of cultured cells on scaffolds confirmed that the combined effect of these factors could be lead to promote better cell adhesion, dispersion, and bone regeneration.

3D printing of microstructured piezoelectric and bioactive PCL-composite scaffolds for bone regeneration

Bone tissue has the ability to self heal, but the treatment of critical size defects and the limited regenerative process in osteoporosis or avascular necrosis demand special medical attention. The field of bone tissue engineering aims to develop new patient-specific solutions for bone repair. In this study, we focus on the fabrication of degradable subchondral bone scaffolds made of highly loaded Polycaprolactone (PCL) using direct ink writing. Barium titanate (BTO) and the bioactive glass 45S5 (BG) were used as filler materials to tailor the material's piezoelectric, mechanical, and bioresponsive properties. The mechanical properties of our composites are in the range of spongy bone, a compressive modulus of around 181 MPa was achieved for PCL/BTO and 98.3 MPa for PCL/BTO/BG scaffolds. The use of 40 vol.% BTO in combination with PCL showed piezoelectric properties in the range of bone tissue with a d33 of 0.75 pC/N. While adding BG decreases the piezoelectric properties, it increases the bioactivity and the osteogenic response of primary human osteoblasts. In summary, these novel material compositions provide a promising approach for developing multiphasic scaffolds for bone tissue engineering. &amp;nbsp;

Optimizing printability and mechanical properties of poly(3-hydroxybutyrate) (P3HB) biocomposite blends and their biological response to Saos-2 cells

Bone tissue engineering requires scaffolds with three-dimensional structures that facilitate vascularization and new tissue growth. 3D printing, especially through fused deposition modeling (FDM), has emerged as an effective method for creating complex structures with high reproducibility. Early research in this area demonstrated the potential of poly(&amp;epsilon;-caprolactone) (PCL) and poly(L-lactide) (PLLA) scaffolds for bone regeneration. Recently, polylactide (PLA) and polyhydroxyalkanoates (PHAs) have garnered attention for their biocompatibility and ability to support cell proliferation. Among PHAs, poly(3-hydroxybutyrate) (P3HB) shows promise due to its intrinsic biocompatibility and resorbability, making it a candidate for FDM-based scaffold fabrication. In the presented study, we aim to develop and optimize a biocompatible P3HB-based composite material for bone tissue engineering, incorporating PLA, hydroxyapatite (HA), and the plasticizer Syncroflex3114 (SN) to enhance mechanical properties and printability. This composite was processed into filaments for 3D printing and characterized through thermal, mechanical, and biological evaluations. Using a design of experiment (DoE) approach, we investigated factors such as temperature performance, warping, degradation, and strength to determine the optimal composition for use in tissue engineering. Four optimal mixture compositions fulfilling the optimization criteria of having the most suitable properties for bone tissue engineering, namely the best printability and maximum mechanical properties,&amp;nbsp; were obtained. The mixtures were optimized specifically for minimum warping coefficient (0.5); maximum flexural strength (66.9 MPa); maximum compression modulus (2.4 GPa); and maximum compression modulus (2.3 GPa) with a warping coefficient of no more than one at the same time. In conclusion, the study shows a new possible way to effectively develop and test 3D printed P3HB-based scaffolds with specifically optimized material properties.

Antisolvent 3D Printing of Gene-Activated Scaffolds for Bone Regeneration.

The use of 3D-printed gene-activated bone grafts represents a highly promising approach in the fields of dentistry and orthopedics. Bioresorbable poly-lactic-co-glycolic acid (PLGA) scaffolds, infused with adenoviral constructs that carry osteoinductive factor genes, may provide an effective alternative to existing bone grafts for the reconstruction of extensive bone defects. This study aims to develop and investigate the properties of 3D scaffolds composed of PLGA and adenoviral constructs carrying the BMP2 gene (Ad-BMP2), both in vitro and in vivo. The elastic modulus of the disk-shaped PLGA scaffolds created using a specialized 3D printer was determined by compressive testing in both axial and radial directions. In vitro cytocompatibility was assessed using adipose-derived stem cells (ADSCs). The ability of Ad-BMP2 to transduce cells was evaluated. The osteoinductive and biocompatible properties of the scaffolds were also assessed in vivo. The Young's modulus of the 3D-printed PLGA scaffolds exhibited comparable values in both axial and radial compression directions, measuring 3.4 ± 0.7 MPa for axial and 3.17 ± 1.4 MPa for radial compression. The scaffolds promoted cell adhesion and had no cytotoxic effect on ADSCs. Ad-BMP2 successfully transduced the cells and induced osteogenic differentiation in vitro. In vivo studies demonstrated that the 3D-printed PLGA scaffolds had osteoinductive properties, promoting bone formation within the scaffold filaments as well as at the center of a critical calvarial bone defect.

An InVivo Assessment of Different Mesenchymal Stromal Cell Tissue Types and Their Differentiation State on a Shape Memory Polymer Scaffold for Bone Regeneration.

A combined biomaterial and cell-based solution to heal critical size bone defects in the craniomaxillofacial area is a promising alternative therapeutic option to improve upon autografting, the current gold standard. A shape memory polymer (SMP) scaffold, composed of biodegradable poly(ε-caprolactone) and coated with bioactive polydopamine, was evaluated with mesenchymal stromal cells (MSCs) derived from adipose (ADSC), bone marrow (BMSC), or umbilical cord (UCSC) tissue in their undifferentiated state or pre-differentiated toward osteoblasts for bone healing in a rat calvarial defect model. Pre-differentiating ADSCs and UCSCs resulted in higher new bone volume fraction (15.69% ± 1.64%) compared to empty (i.e., untreated) defects and scaffold-only (i.e., unseeded) groups (4.41% ± 1.11%). Notably, only differentiated UCSCs exhibited a significant increase in new bone volume, surpassing both undifferentiated UCSCs and unseeded scaffolds. Further, differentiated ADSCs and UCSCs had significantly higher trabecular numbers than their undifferentiated counterparts, unseeded scaffolds, and untreated defects. Although the mineral density regenerated within the unseeded scaffold surpassed that achieved with cell seeding, the connectivity of this bone was diminished, as the regenerated tissue confined itself to the spherical morphology of the scaffold pores. The SMP scaffold alone, with undifferentiated BMSCs, with undifferentiated and differentiated ADSCs, and differentiated UCSCs (29.72 ± 1.49 N) demonstrated significant osseointegration compared to empty defects (14.34 ± 2.21 N) after 12 weeks of healing when assessed by mechanical push-out testing. Based on these results and tissue availability to obtain the cells, pre-differentiated ADSCs and UCSCs emerge as particularly promising candidates when paired with the SMP scaffold for repairing critical size bone defects in the craniofacial skeleton.

Fabrication and evaluation of Zn-EGCG-loaded chitosan scaffolds for bone regeneration: From cellular responses to in vivo performance.

We have synthesized a flavonoid metal complex (FMC) by chelating zinc to epigallocatechin-3-gallate (EGCG), a flavonoid present in green tea and incorporated into chitosan (CS) to form 3D constructs by freeze drying method. Scanning electron microscopy characterized The scaffolds for surface morphology and pore dimensions and depicted the presence of interconnected porous network. The scaffolds exhibited optimal pore size (>50μm), facilitating bone tissue ingrowth and neovascularization. Inclusion of Zn-EGCG into CS matrix improved the mechanical property by increasing compressive strength (0.53±0.045MPa) and reducing enzymatic degradation with controlled swelling. In addition, increased protein adsorption was observed during the initial hour, which is crucial for cell attachment. Furthermore, the FMC inclusion promoted exogenous biomineralization of CS scaffolds as early as 4d in simulated body fluid. Indirect cytotoxicity measurements indicated the scaffolds with Zn-EGCG had no toxic effects on mouse mesenchymal stem cells (mMSCs). Under osteogenic environment, the scaffold promoted calcium deposition of mMSCs by upregulation of ALP activity and increased expression of osteoblast differentiation markers such as Runx2, ColI, OC and OPN. We found that the involvement of miR-15b/smurf-1 signalling pathway behind the osteogenic potential of the scaffold. In vivo assessments using the chick embryo CAM assay showed enhanced angiogenesis and confirmed the scaffold's biocompatibility with no toxicity. Additionally, in a zebrafish scale regeneration model, the scaffold enhanced calcium deposition and osteoblast marker expression, aligning with the in vitro findings. Overall, form the study it is clear that the osteogenic potential of the scaffold is as follows chitosan<EGCG-Chitosan<Zn-EGCG-Chitosan.

Cerebrospinal Fluid-Derived extracellular Vesicle-Inspired Multifunctional bone regeneration scaffold for cranial defect repair

Cerebrospinal Fluid-Derived extracellular Vesicle-Inspired Multifunctional bone regeneration scaffold for cranial defect repair

Development of polymeric composite scaffolds for defective bone repair and regeneration

Bones are vital components of the body that provide soft internal organs and tissues with structure, motion, and safety. Damage to bones can make life challenging. In repairing and regenerating damaged bone, polymeric composite materials significantly contribute to bone tissue engineering. In this article, we described developing porous scaffolds using the freeze-drying process from sodium alginate (SA), polyvinyl alcohol (PVA), and graphene oxide (GO) incorporated with zinc (Zn). These scaffolds were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and universal testing machine (UTM) to investigate their structural analysis, surface morphology, and mechanical behavior, respectively. These scaffolds also exhibited less swelling in phosphate buffer saline (34.73–64.27%) than in aqueous media (42.36–75.92%) with controlled degradation. These scaffolds have potential biomineralization activities, hemocompatibility, and antibacterial activities, which were increased by increasing the Zn amount. All the scaffolds have biocompatibility as they have shown cell viability with mature cell morphology against preosteoblast and HEK-293 cell lines under standard in vitro conditions. The enhanced biological activities of the scaffolds were found by increasing the Zn amount. Thus, newly designed polymeric composite scaffolds would be promising materials to repair and regenerate fractured bone tissue.

Potassium tantalum niobate: Structural insights and biocompatibility for biomedical applications

AbstractThis study explores the biomedical applications of electrically active potassium tantalum niobate (KTN) ceramics (KTa1 − xNbxO3; where x = 0.0, 0.1, 0.3, 0.5, and 0.7), focusing on their dielectric and biological properties for bioelectrets and electroactive scaffolds. Varying Nb concentrations induced a structural shift from cubic to orthorhombic phases, with increased Nb inhibiting grain growth and maintaining stoichiometry. Dielectric analysis across temperatures and frequencies revealed two phase transitions (orthorhombic to tetragonal at 433–453 K and tetragonal to cubic at 653–703 K). Nyquist plots indicated reduced bulk resistance with increasing temperature. The AC conductivity (10−4 S/cm) suggests potential enhancement in bone regeneration scaffolds. Bioactivity assessments showed negative surface charges promoting dense apatite layer formation, while cytocompatibility studies demonstrated robust cell proliferation (&gt;100% by Day 3 for PSVK‐1 and Wi‐38 cell lines). This comprehensive investigation underscores KTN ceramics' promise for biomedical applications in enhancing electrical properties and fostering favorable biological interactions.

Bioactive Coatings on 3D Printed Polycaprolactone Scaffolds for Bone Regeneration: A Novel Murine Femur Defect Model for Examination of the Biomaterial Capacity for Repair

AbstractBone tissue engineering seeks to develop treatment approaches for nonhealing and large bone defects. An ideal biodegradable scaffold will induce and support bone formation. The current study examines bone augmentation in critical‐sized bone defects, using functionalized scaffolds, with the hypothesized potential to induce skeletal cell differentiation. 3D printed, porous poly(caprolactone) trimethacrylate (PCL‐TMA900) scaffolds are applied within a murine femur defect, stabilized by a polyimide intramedullary (IM) pin. The PCL‐TMA900 scaffolds are coated with i) elastin‐like polypeptide (ELP), ii) poly(ethyl acrylate) (PEA)/fibronectin (FN)/bone morphogenetic protein‐2 (PEA/FN/BMP‐2), iii) both ELP and PEA/FN/BMP‐2, or iv) Laponite nanoclay binding BMP‐2. Sequential microcomputed tomography (µCT) and histological analysis are performed. PCL‐TMA900 is robust and biocompatible and when coated with the nanoclay material Laponite and BMP‐2 induce consistent, significant bone formation compared to the uncoated PCL‐TMA900 scaffold. Critically, the BMP‐2 is retained, due to the Laponite, producing bone around the scaffold in the desired shape and volume, compared to bone formation observed with the positive control (collagen sponge/BMP‐2). The ELP and/or PEA/FN/BMP‐2 scaffolds do not demonstrate significant or consistent bone formation. In summary, Laponite/BMP‐2 coated PCL‐TMA900 scaffolds offer a biodegradable, osteogenic construct for bone augmentation with potential for development into a large scale polymer scaffold for clinical translation.

Biological and structural properties of curcumin-loaded graphene oxide incorporated collagen as composite scaffold for bone regeneration.

To address the challenges related to bone defects, including osteoinductivity deficiency and post-implantation infection risk, this study developed the collagen composite scaffolds (CUR-GO-COL) with multifunctionality by integrating the curcumin-loaded graphene oxide with collagen through a freeze-drying-cross-linking process. The morphological and structural characteristics of the composite scaffolds were analyzed, along with their physicochemical properties, including water absorption capacity, water retention rate, porosity, in vitro degradation, and curcumin release. To evaluate the biocompatibility, cell viability, proliferation, and adhesion capabilities of the composite scaffolds, as well as their osteogenic and antimicrobial properties, in vitro cell and bacterial assays were conducted. These assays were designed to assess the impact of the composite scaffolds on cell behavior and bacterial growth, thereby providing insights into their potential for promoting osteogenesis and inhibiting infection. The CUR-GO-COL composite scaffold with a CUR-GO concentration of 0.05% (w/v) exhibits optimal biological compatibility and stable and slow curcumin release rate. Furthermore, in vitro cell and bacterial tests demonstrated that the prepared CUR-GO-COL composite scaffolds enhance cell viability, proliferation and adhesion, and offer superior osteogenic and antimicrobial properties compared with the CUR-GO composite scaffold, confirming the osteogenesis promotion and antimicrobial effects. The introduction of CUR-GO into collagen scaffold creates a bone-friendly microenvironment, and offers a theoretical foundation for the design, investigation and utilization of multifunctional bone tissue biomaterials.

Synergistic enhancement of osteogenesis: silica nanoparticles and proanthocyanidin on bioinspired nanofibrous scaffolds for craniofacial bone regeneration

Synergistic enhancement of osteogenesis: silica nanoparticles and proanthocyanidin on bioinspired nanofibrous scaffolds for craniofacial bone regeneration

Strontium-Substituted Nanohydroxyapatite Containing Biodegradable 3D Printed Composite Scaffolds for Bone Regeneration.

Treatment of large-size bone defects is difficult, and acquiring autografts may be challenging due to limited availability. A synthetic patient-specific bone substitute can be developed by using 3D printing technologies in such cases. In the present study, we have developed photocurable composite resins with poly(trimethylene carbonate) (PTMC) containing a high percentage of biodegradable bioactive strontium-substituted nanohydroxyapatite (SrHA, size 30-70 nm). These photocurable resins have then been employed to develop high-surface-area 3D-printed bone substitutes using the digital light processing (DLP) technique. To enhance the surface area of the 3D-printed substitute, cryogels alone and functionalized with bioactive components of bone morphogenetic protein (BMP) and zoledronic acid (ZA) were filled within the 3D-printed scaffold/substitute. The scaffolds were tested in vitro for biocompatibility and functionality in vivo in two therapeutically relevant rat models with large bone defects (4 mm). The porosities of 3D printed scaffolds were found to be 60.1 ± 0.9%, 72.9 ± 0.5%, and 74.3 ± 1.6% for PTMC, PTMC-HA, and PTMC-SrHA, respectively, which is in the range of cancellous bone (50-95%). The thermogravimetric analysis demonstrated the fabrication of 3D printed composites with HA and SrHA concentrations of 51.5 and 57.4 wt %, respectively, in the PTMC matrix. The tensile Young's modulus (E), compressive moduli, and wettability increased post incorporation of SrHA and HA in the PTMC matrix. In vitro and in vivo results revealed that SrHA integrated into the PTMC matrix exhibited good physicochemical and biological properties. Furthermore, the osteoactive molecule-functionalized 3D printed composite scaffolds were found to have an adequate osteoconductive and osteoinductive surface that has shown increased bone regeneration and defect repair in both tibial and cranial bone defects. Our findings thus support the use of PTMC-SrHA composites as next-generation patient-specific synthetic bioactive biodegradable bone substitutes.

3D Printing Hierarchical Porous Nanofibrous Scaffold for Bone Regeneration.

Current limitations in 3D printing pose significant challenges for the fabrication of hierarchical 3D scaffolds with nanofibrous structures that simulate the natural bone extracellular matrix (ECM) for enhanced bone regeneration. This study presents an innovative approach to 3D printing customized hierarchical porous scaffolds with nanofiber structures using biodegradable nanofibrous microspheres as the bio-ink. In vitro investigations demonstrate that the hierarchical porous architecture substantially enhances cell infiltration and proliferation rates, while the nanofiber topology provides physical cues to guide osteogenic differentiation and ECM deposition. When serving as a cell carrier, the 3D-printed nanofibrous scaffold promotes bone tissue regeneration and integration in vivo. Additionally, the facile and versatile chemical modification facilitates the precise tailoring of the scaffold's functionality. Using nanofibrous microspheres with highly biomimetic and versatile modification properties as the foundational constituent in this universal 3D printing methodology enables comprehensive manipulation of scaffolding biological properties, spanning from macroscopic external morphology to molecular-scale biochemical kinetics, thereby addressing a diverse spectrum of clinical requisites.

3D-printed polycaprolactone/collagen/alginate scaffold incorporating phlorotannin for bone tissue regeneration: Assessment of sub-chronic toxicity

The development of effective scaffolds for bone regeneration is crucial given the increasing demand for innovative solutions to address bone defects and enhance healing process. In this study, a polycaprolactone/fish collagen/alginate (P/FC/A) 3D scaffold incorporating phlorotannin was developed to promote bone tissue regeneration. While the efficacy of the P/FC/A scaffold has been demonstrated through in vitro and in vivo experiments, its sub-chronic toxicity in animal models remains understudied, raising concerns regarding its safety in clinical application. Therefore, this study assessed the sub-chronic toxicity of the P/FC/A scaffold over 12 week using a New Zealand White rabbit model. Our results indicate no significant adverse effects in the group exposed to the P/FC/A scaffold compared with the negative control group implanted with a high-density polyethylene scaffold. These findings underscore the non-toxicity and safety profile of the P/FC/A scaffold, further supporting its potential suitability for clinical use in bone regeneration.

4D printing of smart scaffolds for bone regeneration: a systematic review.

&#xD;As a novel emerging technology, four-dimensional (4D) printing allows 3D-printed materials to change over time. This systematic review is conducted to evaluate the purpose, materials, physiomechanical, and biological properties of 4D-printed scaffolds used for bone tissue engineering.&#xD;Method and materials:&#xD;An electronic search was conducted following the PRISMA 2020 guidelines in PubMed, Scopus, Web of Science, and Google Scholar online databases limited to English articles until April 2024. Studies in which scaffolds were fabricated through 3D printing methods responding to external stimulation were included. The quality of in vitro and in vivo studies was evaluated through the modified CONSORT checklist and SYRCLE's risk of bias tool.&#xD;Results:&#xD;The full text of 57 studies were reviewed, and 15 studies met the inclusion criteria. According to the analyzed studies, most scaffolds responded to temperature changes showing shape memory effect. Polyurethane (PU) and poly(lactic acid) (PLA) were the most common shape memory polymers, and the most common fabrication method used was Fused Deposition Modeling (FDM).&#xD;Conclusion:&#xD;A comprehensive systematic review of the studies from the past 10 years demonstrated several findings: 1) Shape memory, drug delivery, and shape morphing are three general purposes of 4D printing for bone regeneration. 2) Smart materials used for 4D printing mostly consist of shape memory polymers. 3) Temperature changes account for the majority of stimulation used for 4D printing. 4) incorporating 4D printing principles does not have a negative impact on the physiomechanical properties of the designed scaffold. 5) The 4D-printed scaffolds show a higher osteogenic differentiation capacity than their identical 3D-printed structures in terms of bone regeneration.&#xD.

Mechanical Properties of 3D Printed PLA Scaffolds for Bone Regeneration

Abstract The growing interest in biodegradable scaffolds for bone regeneration created a need to investigate new materials suitable for scaffold formation. Poly(lactic acid) (PLA) is a polymer commonly used in biomedical engineering, e.g. in tissue engineering as a biodegradable material. However, the mechanical behavior of PLA along its degradation time is still not explored well. For this reason, the mechanical properties of PLA scaffolds affected by incubation in physiological medium needs to be investigated to show the potential of PLA to be used as a material for biodegradable scaffold formation. The purpose of this research is to determine the mechanical properties of PLA scaffolds before and after incubation, and to apply constitutive material models for further behavior prediction. Two sets of PLA scaffolds were printed by the 3D printer “Prusa i3 MK3S” and sterilized by ultraviolet light and ethanol solution. The first set of specimens was incubated in DMEM (Dulbecco’s Modified Eagle Medium) for 60, 120, and 180 days maintaining 36.5 °C temperature. The mechanical properties of the scaffolds were determined after performing the compression test in the “Mecmesin MultiTest 2.5-i” testing stand with a force applied at two different speed modes. The obtained data was curve fitted with the hyperelastic material models for a model suitability study. The second set of specimens was incubated in PBS (Phosphate Buffered Saline) for 20 weeks and used in a polymer degradation study. The obtained results show that the mechanical properties of PLA scaffolds do not decrease during incubation in physiological medium for a predicted new bone tissue formation period, though hydrolysis starts at the very beginning and increases with time. PLA as a material seems to be suitable for the use in bone tissue engineering as it allows to form biocompatible and biodegradable scaffolds with high mechanical strength, required for effective tissue formation.