3D Printed Polycaprolactone Scaffold Research Articles

3D-printed bone regeneration scaffolds modulate bone metabolic homeostasis through vascularization for osteoporotic bone defects

The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.

Effect of nanodiamonds surface deposition on hydrophilicity, bulk degradation and in-vitro cell adhesion of 3D-printed polycaprolactone scaffolds for bone tissue engineering.

This study was designed to deposit nanodiamonds on 3D-printed PCL scaffolds and evaluate their effect on the surface topography, hydrophilicity, degradation, and in-vitro cell adhesion compared to untreated PCL scaffolds. The PCL scaffold specimens were 3D-printed by fused deposition molding (FDM) technique with specific porosity parameters. The 3D-printed specimens' surfaces were modified by nanodiamonds deposition followed by oxygen plasma post-treatment using a plasma focus (PF) device and a non-thermal atmospheric plasma jet (NTAPJ), respectively. Specimens were evaluated through morphological characterization by field emission scanning electron microscope (FESEM), microstructure characterization by Raman spectroscopy, chemical characterization by Fourier transform infrared (FTIR) spectroscopy, hydrophilicity degree by contact angle and water uptake measurements, and in-vitro degradation measurements (n=6). In addition, in-vitro bone marrow mesenchymal stem cells (BMSCs) adhesion was evaluated quantitatively by Confocal microscopy and qualitatively by FESEM at different time intervals after cell seeding (n=6). The statistical significance level was set at p ≤0.05. The FESEM micrographs, the Raman, and FTIR spectra confirmed the successful surface deposition of nanodiamonds on scaffold specimens. The nanodiamonds treated specimens showed nano-scale features distributed homogeneously across the surface compared to the untreated ones. Also, the nanodiamonds treated specimens revealed a statistically significant smaller contact angle (17.45 ±1.34 degrees), higher water uptake percentage after 24 h immersion in phosphate buffer saline (PBS) (21.56% ±1.73), and higher degradation rate after six months of immersion in PBS (43.92% ±0.77). Moreover, enhanced cell adhesion at all different time intervals was observed in nanodiamonds treated specimens with higher nuclei area fraction percentage (69.87% ±3.97) compared to the untreated specimens (11.46% ±1.34). Surface deposition of nanodiamonds with oxygen-containing functional groups on 3D-printed PCL scaffolds increased their hydrophilicity and degradation rate with significant enhancement of the in-vitro cell adhesion compared to untreated PCL scaffolds.

Effect of 3D-printed polycaprolactone/osteolectin scaffolds on the odontogenic differentiation of human dental pulp cells

Cell-based tissue engineering often requires the use of scaffolds to provide a three-dimensional (3D) framework for cell proliferation and tissue formation. Polycaprolactone (PCL), a type of polymer, has good printability, favorable surface modifiability, adaptability, and biodegradability. However, its large-scale applicability is hindered by its hydrophobic nature, which affects biological properties. Composite materials can be created by adding bioactive materials to the polymer to improve the properties of PCL scaffolds. Osteolectin is an odontogenic factor that promotes the maintenance of the adult skeleton by promoting the differentiation of LepR+ cells into osteoblasts. Therefore, the aim of this study was to evaluate whether 3D-printed PCL/osteolectin scaffolds supply a suitable microenvironment for the odontogenic differentiation of human dental pulp cells (hDPCs). The hDPCs were cultured on 3D-printed PCL scaffolds with or without pores. Cell attachment and cell proliferation were evaluated using EZ-Cytox. The odontogenic differentiation of hDPCs was evaluated by alizarin red S staining and alkaline phosphatase assays. Western blot was used to evaluate the expression of the proteins DSPP and DMP-Results: The attachment of hDPCs to PCL scaffolds with pores was significantly higher than to PCL scaffolds without pores. The odontogenic differentiation of hDPCs was induced more in PCL/osteolectin scaffolds than in PCL scaffolds, but there was no statistically significant difference. 3D-printed PCL scaffolds with pores are suitable for the growth of hDPCs, and the PCL/osteolectin scaffolds can provide a more favorable microenvironment for the odontogenic differentiation of hDPCs.

Evaluation of new bone formation in critical-sized rat calvarial defect using 3D printed polycaprolactone/tragacanth gum-bioactive glass composite scaffolds

Critical-sized bone defects are a major challenge in reconstructive bone surgery and usually fail to be treated due to limited remaining bone quality and extensive healing time. The combination of 3D-printed scaffolds and bioactive materials is a promising approach for bone tissue regeneration. In this study, 3D-printed alkaline-treated polycaprolactone scaffolds (M-PCL) were fabricated and integrated with tragacanth gum- 45S5 bioactive glass (TG-BG) to treat critical-sized calvarial bone defects in female adult Wistar rats. After a healing period of four and eight weeks, the new bone of blank, M-PCL, and M-PCL/TG-BG groups were harvested and assessed. Micro-computed tomography, histological, biochemical, and biomechanical analyses, gene expression, and bone matrix formation were used to assess bone regeneration. The micro-computed tomography results showed that the M-PCL/TG-BG scaffolds not only induced bone tissue formation within the bone defect but also increased BMD and BV/TV compared to blank and M-PCL groups. According to the histological analysis, there was no evidence of bony union in the calvarial defect regions of blank groups, while in M-PCL/TG-BG groups bony integration and repair were observed. The M-PCL/TG-BG scaffolds promoted the Runx2 and collagen type I expression as compared with blank and M-PCL groups. Besides, the bone regeneration in M-PCL/TG-BG groups correlated with TG-BG incorporation. Moreover, the use of M-PCL/TG-BG scaffolds promoted the biomechanical properties in the bone remodeling process. These data demonstrated that the M-PCL/TG-BG scaffolds serve as a highly promising platform for the development of bone grafts, supporting bone regeneration with bone matrix formation, and osteogenic features. Our results exhibited that the 3D-printed M-PCL/TG-BG scaffolds are a promising strategy for successful bone regeneration.

Protective effects of lutein against phone screen light-induced damage on 3D bioprinted retinal pigment epithelium monolayers

Cumulative light exposure, including electronic device radiation, may induce retinal pigment epithelium (RPE)-related retinal diseases, potentially mitigated by lutein. However, there is limited 3D RPE monolayer model to study the effect of phytochemicals on their activity and action mechanisms in vitro. Here, we present a method using a monolayer RPE tissue model on a 3D-printed polycaprolactone scaffold. Six-hour of phone screen light increased reactive oxygen species (ROS) in RPE cells, leading to oxidative stress, cytotoxicity, and inhibited metabolism. Pre-treating RPE cells (24 h) with 0.5 µM lutein reduced ROS levels and maintained viability under the same light exposure. Additionally, lutein demonstrated protective effects on crucial RPE functions, including phagocytosis and the retinal-blood barrier. This study underscores the importance of optimal lutein content in shielding RPE from phone screen light damage, and our model holds promise for evaluating the efficacy of antioxidants against light radiation.

Biomimetic Mineralized 3D-Printed Polycaprolactone Scaffold Induced by Self-Adaptive Nanotopology to Accelerate Bone Regeneration.

Three-dimensional (3D)-printed biodegradable polymer scaffolds are at the forefront of personalized constructs for bone tissue engineering. However, it remains challenging to create a biological microenvironment for bone growth. Herein, we developed a novel yet feasible approach to facilitate biomimetic mineralization via self-adaptive nanotopography, which overcomes difficulties in the surface biofunctionalization of 3D-printed polycaprolactone (PCL) scaffolds. The building blocks of self-adaptive nanotopography were PCL lamellae that formed on the 3D-printed PCL scaffold via surface-directed epitaxial crystallization and acted as a linker to nucleate and generate hydroxyapatite crystals. Accordingly, a uniform and robust mineralized layer was immobilized throughout the scaffolds, which strongly bound to the strands and had no effect on the mechanical properties of the scaffolds. In vitro cell culture experiments revealed that the resulting scaffold was biocompatible and enhanced the proliferation and osteogenic differentiation of mouse embryolous osteoblast cells. Furthermore, we demonstrated that the resulting scaffold showed a strong capability to accelerate in vivo bone regeneration using a rabbit bone defect model. This study provides valuable opportunities to enhance the application of 3D-printed scaffolds in bone repair, paving the way for translation to other orthopedic implants.

MicroRNA-200c Release from Gelatin-Coated 3D-Printed PCL Scaffolds Enhances Bone Regeneration.

The fabrication of clinically relevant synthetic bone grafts relies on combining multiple biodegradable biomaterials to create a structure that supports the regeneration of defects while delivering osteogenic biomolecules that enhance regeneration. MicroRNA-200c (miR-200c) functions as a potent osteoinductive biomolecule to enhance osteogenic differentiation and bone formation; however, synthetic tissue-engineered bone grafts that sustain the delivery of miR-200c for bone regeneration have not yet been evaluated. In this study, we created novel, multimaterial, synthetic bone grafts from gelatin-coated 3D-printed polycaprolactone (PCL) scaffolds. We attempted to optimize the release of pDNA encoding miR-200c by varying gelatin types, concentrations, and polymer crosslinking materials to improve its functions for bone regeneration. We revealed that by modulating gelatin type, coating material concentration, and polymer crosslinking, we effectively altered the release rates of pDNA encoding miR-200c, which promoted osteogenic differentiation in vitro and bone regeneration in a critical-sized calvarial bone defect animal model. We also demonstrated that crosslinking the gelatin coatings on the PCL scaffolds with low-concentration glutaraldehyde was biocompatible and increased cell attachment. These results strongly indicate the potential use of gelatin-based systems for pDNA encoding microRNA delivery in gene therapy and further demonstrate the effectiveness of miR-200c for enhancing bone regeneration from synthetic bone grafts.

3D-printed PCL framework assembling ECM-inspired multi-layer mineralized GO-Col-HAp microscaffold for in situ mandibular bone regeneration

BackgroundIn recent years, natural bone extracellular matrix (ECM)-inspired materials have found widespread application as scaffolds for bone tissue engineering. However, the challenge of creating scaffolds that mimic natural bone ECM’s mechanical strength and hierarchical nano-micro-macro structures remains. The purposes of this study were to introduce an innovative bone ECM-inspired scaffold that integrates a 3D-printed framework with hydroxyapatite (HAp) mineralized graphene oxide-collagen (GO-Col) microscaffolds and find its application in the repair of mandibular bone defects.MethodsInitially, a 3D-printed polycaprolactone (PCL) scaffold was designed with cubic disks and square pores to mimic the macrostructure of bone ECM. Subsequently, we developed multi-layer mineralized GO-Col-HAp microscaffolds (MLM GCH) to simulate natural bone ECM's nano- and microstructural features. Systematic in vitro and in vivo experiments were introduced to evaluate the ECM-inspired structure of the scaffold and to explore its effect on cell proliferation and its ability to repair rat bone defects.ResultsThe resultant MLM GCH/PCL composite scaffolds exhibited robust mechanical strength and ample assembly space. Moreover, the ECM-inspired MLM GCH microscaffolds displayed favorable attributes such as water absorption and retention and demonstrated promising cell adsorption, proliferation, and osteogenic differentiation in vitro. The MLM GCH/PCL composite scaffolds exhibited successful bone regeneration within mandibular bone defects in vivo.ConclusionsThis study presents a well-conceived strategy for fabricating ECM-inspired scaffolds by integrating 3D-printed PCL frameworks with multilayer mineralized porous microscaffolds, enhancing cell proliferation, osteogenic differentiation, and bone regeneration. This construction approach holds the potential for extension to various other biomaterial types.Graphical

Surface micropatterning of 3D printed PCL scaffolds promotes osteogenic differentiation of BMSCs and regulates macrophage M2 polarization

Micropatterned structures on the surface of materials possessing biomimetic properties to mimic the extracellular matrix and induce cellular behaviors have been widely studied. However, it is still a major challenge to obtain internally stable and controllable micropatterned 3D scaffolds for bone repair and regeneration. In this study, 3D scaffolds with regular grating arrays using polycaprolactone (PCL) as a matrix material were prepared by combining 3D printing and soft lithography, and the effects of grating micropatterning on osteogenic differentiation of BMSCs and M1/M2 polarization of macrophages were investigated. The results showed that compared with the planar group and the 30um grating spacing group, PCL with a grating spacing of 20um significantly promoted the osteogenic differentiation of BMSCs, induced the polarization of RAW264.7 cells toward M2 type, and suppressed the expression of M1-type pro-inflammatory genes and markers. In conclusion, we successfully constructed PCL-based three-dimensional scaffolds with stable and controllable micrographs (grating arrays) inside, which possess excellent osteogenic properties and promote the formation of an immune microenvironment conducive to osteogenesis. This study is a step forward to the exploration of bone-filling materials affecting cell behavior, and makes a new contribution to the provision of high-quality materials.

Surface functionalization of 3D printed poly-ε-caprolactone by ultrashort laser mirostructuring and ZnO nanolayer deposition

Due to its mechanical properties and good biocompatibility, polycaprolactone (PCL) is a promising material for bone tissue regeneration. However, a major limitation to its use remains the lack of inherent antimicrobial properties and its susceptibility to bacterial colonisation and biofilm formation. A potent strategy for overcoming such issues is surface functionalisation at micro and nano level, which can have a great impact on cell-surface interaction without affecting the integrity of the material. This study presents a novel methodology for surface modification of polymers combining ultrashort laser microstructuring and atomic layer deposition of ZnO. For this purpose, the surface of 3D printed PCL scaffolds was treated with a femtosecond laser (λ=800 nm; τ=75 fs) in order to develop parallel microchannels onto which ZnO nanolayers were further deposited. The presence of ZnO on the laser structured and unstructured scaffolds was detected by X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDX). Both methods confirmed the successful layering as EDX further highlighted a trend that ZnO built up substantially more at the bottom of the microchannels rather than at the top of them. The obtained results would allow proceeding to the next step of the study – investigating the antimicrobial effect of the developed interfaces.

Nano-Topographically Guided, Biomineralized, 3D-Printed Polycaprolactone Scaffolds with Urine-Derived Stem Cells for Promoting Bone Regeneration.

Currently, biomineralization is widely used as a surface modification approach to obtain ideal material surfaces with complex hierarchical nanostructures, morphologies, unique biological functions, and categorized organizations. The fabrication of biomineralized coating for the surfaces of scaffolds, especially synthetic polymer scaffolds, can alter surface characteristics, provide a favorable microenvironment, release various bioactive substances, regulate the cellular behaviors of osteoblasts, and promote bone regeneration after implantation. However, the biomineralized coating fabricated by immersion in a simulated body fluid has the disadvantages of non-uniformity, instability, and limited capacity to act as an effective reservoir of bioactive ions for bone regeneration. In this study, in order to promote the osteoinductivity of 3D-printed PCL scaffolds, we optimized the surface biomineralization procedure by nano-topographical guidance. Compared with biomineralized coating constructed by the conventional method, the nano-topographically guided biomineralized coating possessed more mineral substances and firmly existed on the surface of scaffolds. Additionally, nano-topographically guided biomineralized coating possessed better protein adsorption and ion release capacities. To this end, the present work also demonstrated that nano-topographically guided biomineralized coating on the surface of 3D-printed PCL scaffolds can regulate the cellular behaviors of USCs, guide the osteogenic differentiation of USCs, and provide a biomimetic microenvironment for bone regeneration.

Interactions of neural-like cells with 3D-printed polycaprolactone with different inner diameters for neural regeneration

Background/purposePeripheral neural regeneration is an interesting and challenging field. The aim of this study was to investigate the interactions of neural-like PC12 cells and Poly-D-Lysine (PDL)-coated 3D-printed polycaprolactone (PCL) scaffolds with different inner diameters of half tubular array (HTA) (0, 200, 300, and 400 μm), respectively. Materials and methodsThis study used the fused deposition modeling (FDM) technique with 3D-printing to fabricate the thermoplastic polymer. Scaffold properties were measured by mechanical testing, and coating quality was observed under a scanning electron microscope (SEM). PC12 cell biocompatibility was examined by an MTT assay. Cell differentiation was evaluated by immunofluorescence staining. ResultsThe cell viability of PC12 cells on PDL-coated PCL scaffolds with a 200-μm inner diameter of HTA was shown with significant differences (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001) than other PCL groups at all experimental dates. The SEM observation showed that PDL-coated PCL scaffolds with 200-μm inner diameters of HTA promoted cell adhesion. An immunofluorescence staining of PC12 cells on the PDL-coated PCL scaffold with a 200-μm inner diameter of the HTA group showed that it stimulated PC12 cells for neurite formation much better than the other groups. ConclusionA PDL-coated PCL scaffold with a 200-μm inner diameter of HTA can promote the growth and differentiation of PC12 cells better than other groups. It indicated that PDL-coated PCL scaffolds with a 200-μm inner diameter HTA can be used for further neural regeneration application.

THE IMPACT OF METABOLISM DYSREGULATION IN SCAFFOLD-GUIDED LARGE-VOLUME BONE REGENERATION

The ability of the body to constantly maintain metabolism homeostasis while fulling the heightened energy and macromolecule demand is crucial to ensure successful tissue healing outcomes. Studies investigating the local metabolic environment during healing are scarce to date. Here, using Type 2 Diabetes (T2D) as a study model, we investigate the impact of metabolism dysregulation on scaffold-guided large-volume bone regeneration. Our study treated wild-type or T2D rats with 5 mm critical-sized femoral defects with 3D-printed polycaprolactone (PCL) scaffolds with 70% porosity. Metabolomics was leveraged for a holistic view of metabolism alteration as healing progress and correlated to regenerated bone tissue volume and quality assessed using micro-computed tomography (µ-CT), histology, and immunohistology. Semi-targeted metabolomics analysis indicated dysregulation in the glycolysis and TCA cycle – the main energy production pathways, in T2D compared to healthy animals. The abundance of metabolites substrates, i.e., amino acids – for protein/ extracellular matrix synthesis was also affected in T2D. Tissue-level metabolites observations aligned with morphological observation with less newly formed bone observed in T2D than wild-type rats. This study enlightens the metabolism landscape during scaffold-guided large-volume bone regeneration in wild-type vs. T2D to further guide the personalization of the scaffold to drive successful regeneration.

Internal and external co-induction pineal 3D printed scaffolds for bone and blood vessel regeneration

The precise structural design and reproducible manufacturing advantages of the 3D printed scaffold make it attract attention in clinical applications. However, the inability of scaffolds to achieve internal and external co-induced vascularized osteogenesis limits their application. After observing the ingenious and functionalized structural combination of "pinecone", this study prepared hydrogel microspheres encapsulating strontium ranelate (SrR)-dendrimer (PAMAM) as a functionalized "pine nuts" through microfluidic technology. The 3D-printed Polycaprolactone (PCL) scaffold was used as a framework in which hydrogel microspheres and a 3D-printed scaffold were cleverly combined. In this pinecone 3D-scaffold system, the slow release of SrR is beneficial to promote vascularization and osteogenic differentiation inside and outside the scaffold. Furthermore, the rat femoral defect model verified that the pinecone scaffold promoting the formation of internal vascular network, osteogenic differentiation and shortening the bone repair time in vivo. In summary, this pinecone degradable biomimetic composite scaffold with internal osteogenic differentiation and vascular activation functions has great potential for clinical demand in segmental bone defects.

Enhancing bone tissue engineering with 3D-Printed polycaprolactone scaffolds integrated with tragacanth gum/bioactive glass

Tissue-engineered bone substitutes, characterized by favorable physicochemical, mechanical, and biological properties, present a promising alternative for addressing bone defects. In this study, we employed an innovative 3D host-guest scaffold model, where the host component served as a mechanical support, while the guest component facilitated osteogenic effects. More specifically, we fabricated a triangular porous polycaprolactone framework (host) using advanced 3D printing techniques, and subsequently filled the framework's pores with tragacanth gum-45S5 bioactive glass as the guest component. Comprehensive assessments were conducted to evaluate the physical, mechanical, and biological properties of the designed scaffolds. Remarkably, successful integration of the guest component within the framework was achieved, resulting in enhanced bioactivity and increased strength. Our findings demonstrated that the scaffolds exhibited ion release (Si, Ca, and P), surface apatite formation, and biodegradation. Additionally, in vitro cell culture assays revealed that the scaffolds demonstrated significant improvements in cell viability, proliferation, and attachment. Significantly, the multi-compartment scaffolds exhibited remarkable osteogenic properties, indicated by a substantial increase in the expression of osteopontin, osteocalcin, and matrix deposition. Based on our results, the framework provided robust mechanical support during the new bone formation process, while the guest component matrix created a conducive micro-environment for cellular adhesion, osteogenic functionality, and matrix production. These multi-compartment scaffolds hold great potential as a viable alternative to autografts and offer promising clinical applications for bone defect repair in the future.

3D-Printed Medical-Grade Polycaprolactone (mPCL) Scaffold for the Surgical Treatment of Vaginal Prolapse and Abdominal Hernias.

The expected outcome after a scaffold augmented hernia repair is the regeneration of a tissue composition strong enough to sustain biomechanical function over long periods. It is hypothesised that melt electrowriting (MEW) medical-grade polycaprolactone (mPCL) scaffolds loaded with platelet-rich plasma (PRP) will enhance soft tissue regeneration in fascial defects in abdominal and vaginal sheep models. A pre-clinical evaluation of vaginal and abdominal hernia reconstruction using mPCL mesh scaffolds and polypropylene (PP) meshes was undertaken using an ovine model. Each sheep was implanted with both a PP mesh (control group), and a mPCL mesh loaded with PRP (experimental group) in both abdominal and vaginal sites. Mechanical properties of the tissue-mesh complexes were assessed with plunger tests. Tissue responses to the implanted meshes were evaluated via histology, immunohistochemistry and histomorphometry. At 6 months post-surgery, the mPCL mesh was less stiff than the PP mesh, but stiffer than the native tissue, while showing equitable collagen and vascular ingrowth when compared to PP mesh. The results of this pilot study were supportive of mPCL as a safe and effective biodegradable scaffold for hernia and vaginal prolapse repair, hence a full-scale long-term study (over 24-36 months) with an adequate sample size is recommended.

Construction of a novel cell-free tracheal scaffold promoting vascularization for repairing tracheal defects

Functional vascularization is crucial for maintaining the long-term patency of tissue-engineered trachea and repairing defective trachea. Herein, we report the construction and evaluation of a novel cell-free tissue-engineered tracheal scaffold that effectively promotes vascularization of the graft. Our findings demonstrated that exosomes derived from endothelial progenitor cells (EPC-Exos) enhance the proliferation, migration, and tube formation of endothelial cells. Taking advantage of the angiogenic properties of EPC-Exos, we utilized methacrylate gelatin (GelMA) as a carrier for endothelial progenitor cell exosomes and encapsulated them within a 3D-printed polycaprolactone (PCL) scaffold to fabricate a composite tracheal scaffold. The results demonstrated the excellent angiogenic potential of the methacrylate gelatin/vascular endothelial progenitor cell exosome/polycaprolactone tracheal scaffold. Furthermore, in vivo reconstruction of tracheal defects revealed the capacity of this composite tracheal stent to remodel vasculature. In conclusion, we have successfully developed a novel tracheal stent composed of methacrylate gelatin/vascular endothelial progenitor exosome/polycaprolactone, which effectively promotes angiogenesis for tracheal repair, thereby offering significant prospects for clinical and translational medicine.

Enhancing bone regeneration with bionic hydrolysis and biomimetic polydopamine coating on 3D-printed PCL scaffolds: A comparative study

Surface modification can enhance the biological properties of polycaprolactone (PCL) scaffolds. In this study, bionic hydrolysis and biomimetic polydopamine (PDA) coating were investigated, individually and in combination, to enhance the bioactivity of inner cube 3D-printed PCL scaffolds. The modified scaffolds were evaluated for their bioactivity, and the underlying mechanism was studied based on their physiochemical properties. The modifications significantly improved the surface roughness, hydrophilicity, surface adhesion ability, and biological properties of the scaffolds. The hydrolyzed PCL scaffolds exhibited micro-cracks and pits on their surface, with carboxyl and hydroxyl groups present. PDA, in the form of micro-particles with phenolic hydroxyl and amino groups, was coated onto the PDA-coated scaffolds. The combination-treated scaffolds had shallower pits, smaller particles, and lower levels of phenolic hydroxyl and amino groups. PDA coating demonstrated the best properties in promoting the adhesion, proliferation, and osteogenesis of rat bone marrow mesenchymal stem cells. Although the combination-treated scaffolds showed better cell proliferation than the hydrolyzed scaffolds, they did not exhibit a synergistic effect on osteogenic induction, instead weakening the osteogenic induction ability of the PDA-coating and hydrolysis treatments. Therefore, the material’s characteristics and the substantial variation of different chemical reactions must be considered during biological material modification.

3D-printed polycaprolactone scaffolds coated with beta tricalcium phosphate for bone regeneration

3D-printing technology is an important tool for the bone tissue engineering (BTE). The aim of this study was to investigate the interaction of polycaprolactone (PCL) scaffolds and modified mesh PCL coated with beta TCP (PCL/β-TCP) scaffolds with MG-63. This study used the fused deposition modeling (FDM) technique with the 3D printing technique to fabricate the thermoplastic polymer and composite scaffolds. Scaffold structure and coating quality were observed under a scanning electron microscope (SEM). MG-63 cells were injected and attached to the mesh-manufactured PCL scaffolds. The biocompatibility of mesh structured PCL and PCL/β-TCP scaffolds could be examined by measuring the viability of MG-63 cells of MTT assay. Bone cell differentiation was evaluated ALP activity by mineralization assay. The results showed that both mesh PCL scaffolds and PCL/β-TCP scaffolds were non-toxic to the cells. The ALP activities of cells in PCL/β-TCP scaffolds groups were significant differences and better than PCL groups in all groups at all experimental dates. The mineralization process was time-dependent, and significantly higher mineralization of osteosarcoma cells was observed on PCL/β-TCP scaffolds at experimental dates. We concluded that both meshes structured PCL and PCL/β-TCP scaffolds could promote the MG-63 cell growth, and PCL/β-TCP was better than the PCL scaffolds for the outcome of MG63 cell differentiation and mineralization.

A cell-free tissue-engineered tracheal substitute with sequential cytokine release maintained airway opening in a rabbit tracheal full circumferential defect model

In this study, a cell-free tissue-engineered tracheal substitute was developed, which is based on a 3D-printed polycaprolactone scaffold coated with a gelatin-methacryloyl (GelMA) hydrogel, with transforming growth factor-β1 (TGF-β) and stromal cell-derived factor-1α (SDF-1) sequentially embedded, to facilitate cell recruitment and differentiation toward chondrocyte-phenotype. TGF-β was loaded onto polydopamine particles, and then encapsulated into the GelMA together with SDF-1, and called G/S/P@T, which was used to coat 3D-printed PCL scaffold to form the tracheal substitute. A rapid release of SDF-1 was observed during the first week, followed by a slow and sustained release of TGF-β for approximately four weeks. The tracheal substitute significantly promoted the recruitment of mesenchymal stromal cells (MSCs) or human bronchial epithelial cells in vitro, and enhanced the ability of MSCs to differentiate towards chondrocyte phenotype. Implantation of the tissue-engineered tracheal substitute with a rabbit tracheal anterior defect model improved regeneration of airway epithelium, recruitment of endogenous MSCs and expression of markers of chondrocytes at the tracheal defect site. Moreover, the tracheal substitute maintained airway opening for 4 weeks in a tracheal full circumferential defect model with airway epithelium coverage at the defect sites without granulation tissue accumulation in the tracheal lumen or underneath. The promising results suggest that this simple, cell-free tissue-engineered tracheal substitute can be used directly after tracheal defect removal and should be further developed towards clinical application.