Polycaprolactone Scaffolds Research Articles

Enhanced In Vitro Biocompatible Polycaprolactone/Nano-Hydroxyapatite Scaffolds with Near-Field Direct-Writing Melt Electrospinning Technology.

Polycaprolactone (PCL) scaffold is a common biological material for tissue engineering, owing to its good biocompatibility, biodegradability and plasticity. However, it is not suitable for osteoblast adhesion and regeneration of bone tissue due to its non-biological activity, poor mechanical strength, slow degradation speed, smooth surface and strong hydrophobicity. To improve the mechanical properties and biocompatibility of PCL scaffold, the PCL/nHA scaffolds were prepared by melting and blending different proportions of nano-hydroxyapatite (nHA) with PCL by the near-field direct-writing melt electrospinning technology in this study. The morphology, porosity, mechanical properties and in vitro biocompatibility of the PCL/nHA scaffolds were studied. The results showed that when the proportion of nHA was less than or equal to 25%, PCL/nHA composite scaffolds were easily formed in which bone marrow mesenchymal stem cells proliferated successfully. When the proportion of nHA was 15%, the PCL/nHA composite scaffolds had excellent structural regularity, good fiber uniformity, outstanding mechanical stability and superior biocompatibility. The PCL/nHA composite scaffolds were ideal scaffold materials, which would broaden their applications for bone tissue engineering.

Polycaprolactone-Based 3D-Printed Scaffolds as Potential Implant Materials for Tendon-Defect Repair.

Chronic tendon ruptures are common disorders in orthopedics. The conventional surgical methods used to treat them often require the support of implants. Due to the non-availability of suitable materials, 3D-printed polycaprolactone (PCL) scaffolds were designed from two different starting materials as suitable candidates for tendon-implant applications. For the characterization, mechanical testing was performed. To increase their biocompatibility, the PCL-scaffolds were plasma-treated and coated with fibronectin and collagen I. Cytocompatibility testing was performed using L929 mouse fibroblasts and human-bone-marrow-derived mesenchymal stem cells. The mechanical testing showed that the design adaptions enhanced the mechanical stability. Cell attachment was increased in the plasma-treated specimens compared to the control specimens, although not significantly, in the viability tests. Coating with fibronectin significantly increased the cellular viability compared to the untreated controls. Collagen I treatment showed an increasing trend. The desired cell alignment and spread between the pores of the construct was most prominent on the collagen-I-coated specimens. In conclusion, 3D-printed scaffolds are possible candidates for the development of tendon implants. Enhanced cytocompatibility was achieved through surface modifications. Although adaptions in mechanical strength still require alterations in order to be applied to human-tendon ruptures, we are optimistic that a suitable implant can be designed.

New dual-function in situ bone repair scaffolds promote osteogenesis and reduce infection

BackgroundThe treatment of infectious bone defects is a difficult problem to be solved in the clinic. In situ bone defect repair scaffolds with anti-infection and osteogenic abilities can effectively deal with infectious bone defects. In this study, an in situ polycaprolactone (PCL) scaffold containing ampicillin (Amp) and Mg microspheres was prepared by 3D printing technology.ResultsMg and Amp were evenly distributed in PCL scaffolds and could be released slowly to the surrounding defect sites with the degradation of scaffolds. In vitro experiments demonstrated that the PCL scaffold containing Mg and Amp (PCL@Mg/Amp) demonstrated good cell adhesion and proliferation. The osteogenic genes collagen I (COL-I) and Runx2 were upregulated in cells grown on the PCL@Mg/Amp scaffold. The PCL@Mg/Amp scaffold also demonstrated excellent antibacterial ability against E. coli and S. aureus. In vivo experiments showed that the PCL@Mg/Amp scaffold had the strongest ability to promote tibial defect repair in rats compared with the other groups of scaffolds.ConclusionsThis kind of dual-function in situ bone repair scaffold with anti-infection and osteogenic abilities has good application prospects in the field of treating infectious bone defects.

Electrospun PCL/fibrin scaffold as a bone implant improved the differentiation of human adipose-derived mesenchymal stem cells into osteo-like cells

Bone remodeling is not able to repair the major injuries caused by trauma, cancer, etc. Bone tissue engineering is aimed to provide implants for bone repair or replacement. To approach such a purpose, polymeric scaffolds along with stem cells are used to fabricate a supportive matrix mimicking in vivo microenvironment. Here, we developed an in vivo-like matrix based on polycaprolactone (PCL) and fibrin to enhance the differentiation of human adipose-derived mesenchymal stem cells into osteo-like cells (AD-MSCs). PCL scaffold was fabricated by electrospinning and coated with fibrin. AD-MSCs were cultured and differentiate on PCL and PCL/fibrin. The viability of cultured cells in comparison with tissue culture plate (TCPS) was evaluated by MTT assay on days 1, 2, and 3 of differentiation. The differentiation was compared to TCPS on days 7, 14, and 21 of differentiation. To evaluate the differentiation efficiency, calcium content, alkaline phosphatase (ALP), and expression of RUNX-2, Collagene-I, Osteocalcin, and Osteonectin were assessed in differentiated cells. A slight increase in cell viability was observed in the TCPS group on day 3 of differentiation. Higher calcium content and ALP activity were observed in PCL and PCL/fibrin groups, respectively. The expression of osteogenic genes was higher in the PCL/fibrin group on days 7, 14, and 21 of differentiation. It seems PCL acts synergistically with fibrin to make an in vivo-like microenvironment and enhanced the differentiation of AD-MSCs into osteo-like cells.

Breast Tissue Restoration after the Partial Mastectomy Using Polycaprolactone Scaffold.

As breast conserving surgery increases in the surgical treatment of breast cancer, partial mastectomy is also increasing. Polycaprolactone (PCL) is a polymer that is used as an artifact in various parts of the human body based on the biocompatibility and mechanical properties of PCL. Here, we hypothesized that a PCL scaffold can be utilized for the restoration of breast tissue after a partial mastectomy. To demonstrate the hypothesis, a PCL scaffold was fabricated by 3D printing and three types of spherical PCL scaffold including PCL scaffold, PCL scaffold with collagen, and the PCL scaffold with breast tissue fragment were implanted in the rat breast defect model. After 6 months of implantation, the restoration of breast tissue was observed in the PCL scaffold and the expression of collagen in the PCL scaffold with collagen was seen. The expression of TNF-α was significantly increased in the PCL scaffold, but the expression of IL-6 showed no significant difference in all groups. Through this, it showed the possibility of using it as a method to conveniently repair tissue defects after partial mastectomy of the human body.

The novel approach to physico-chemical modification and cytocompatibility enhancement of fibrous polycaprolactone (PCL) scaffolds using soft X-ray/extreme ultraviolet (SXR/EUV) radiation and low-temperature, SXR/EUV induced, nitrogen and oxygen plasmas

The fundamental aspect of the fabrication of microporous, fibrous biomaterials in form of scaffolds is the optimization of their surface properties to enhance cellular response. In this work, a novel approach to physico-chemical modification and bioactivity enhancement of electrospun fibrous polycaprolactone (PCL) nonwovens using soft X-ray/extreme ultraviolet (SXR/EUV) irradiation and exposure to a low-temperature, SXR/EUV induced, nitrogen and oxygen plasmas is presented for the first time.Chemical alterations and morphology of the fibrous structure of irradiated PCL mats were examined using X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), respectively. The impact of introduced changes on viability, morphology, and adhesion of L929 mouse fibroblasts was examined. It was found that simultaneous interaction of SXR/EUV radiation and N2 or O2 photoionized plasmas led to strong chemical decomposition of the surface of fibrous PCL mats. Also, mats’ spatial porous structure was not damaged and the fibers were not broken or fused. All modified samples demonstrated cyto-compatible and non-cytotoxic properties. Enhancement of L929 cell adhesion and increased proliferation were also observed.

On-demand delivery of protein drug from 3D-printed implants.

Here, we constructed 3D-printed multiunit implants to enable remote light-controlled protein drug delivery in a spatiotemporal manner. Multiunit implants were designed to be 3D printed using polycaprolactone, lauric acid, and melanin as a matrix, and a polycaprolactone scaffold as a multiunit divider. As a model drug, insulin was loaded to each unit of the implant. The 3D printing yielded a rectangular matrix with multiunit sectors segregated by polycaprolactone lanes. Irradiation with near infrared light (NIR) triggered controlled release of insulin from the irradiated locus: Upon NIR irradiation, heat generated from the melanin melted the polycaprolactone/lauric acid matrix to release insulin from the scaffold. In the absence of melanin in the matrix, the implant did not show NIR-responsive insulin release. When lauric acid was absent from the matrix, the NIR-irradiated unit did not undergo dismantling. When the insulin-loaded multiunit implant was applied to a mouse diabetic model and irradiated with NIR, repetitive insulin release resulted in an efficient decrease of the blood glucose level over multiple days. Together, these results suggest that 3D printing technology-based multi-dosing of insulin on demand can enable convenient treatment of diabetes through external NIR irradiation, potentially avoiding the pain and discomfort of repeated insulin injections.

3D-printed composite scaffold with gradient structure and programmed biomolecule delivery to guide stem cell behavior for osteochondral regeneration.

The fabrication of osteochondral scaffolds with both structural and biochemical cues to regulate endogenous bone marrow-derived mesenchymal stem cells (BMSCs) behavior for cartilage and subchondral bone regeneration is still a challenge. To this end, a composite scaffold (BE-PSA) with gradient structure and programmed biomolecule delivery was prepared by fused deposition modeling (FDM) 3D printing and multi-material-based modification. The 3D-printed polycaprolactone (PCL) scaffold included upper pores of 200μm for cartilage regeneration and lower pores of 400μm for bone regeneration. For a sequential modulation of BMSCs behavior, fast-degrading sodium alginate (SA) hydrogel was used to deliver a burst release of E7 peptide to enhance BMSCs migration within 72h, while a slowly-degrading silk fibroin (SF) porous matrix was used to provide a sustained release of B2A peptide to improve BMSCs dual-lineage differentiation lasting for >300h, depending on the different degradation rates of SA hydrogel and SF matrix. The BE-PSA scaffold had good biocompatibility and could improve the migration and osteogenic/chondrogenic differentiation of BMSCs. Benefiting from the synergistic effects of spatial structures and programmed biomolecule delivery, the BE-PSA scaffold showed enhanced cartilage and subchondral bone regeneration in rabbit osteochondral defect model. This work not only provides a promising scaffold to guide BMSCs behavior for osteochondral regeneration but also offers a method for the fabrication of tissue engineering biomaterials based on the structural and biochemical modification.

Direct 3D printing of decellularized matrix embedded composite polycaprolactone scaffolds for cartilage regeneration.

Treatment options for large osteochondral injuries (OCIs) are limited by donor tissue scarcity, morbidity, and anatomic mismatch. 3D printing technology can produce patient-specific scaffolds to address these large defects. Thermoplastics like polycaprolactone (PCL) offer necessary mechanical properties, but lack bioactivity. We fabricated 3D printed PCL scaffolds embedded with polylactic acid microspheres containing decellularized cartilage matrix (DM). DM incorporation within polylactic acid microspheres prevented its thermal degradation during the 3D printing process. The scaffolds replicated the mechanical properties of native cartilage and demonstrated controlled release of DM proteins. Human mesenchymal stem cells (hMSCs) seeded on the composite scaffolds with DM and cultured in basal media self-assembled into aggregates mimicking mesenchymal condensates during embryonic development. The DM composite scaffolds also induced higher expression of biochemical markers of cartilage development than controls, providing evidence for their translational application in the treatment of OCIs. The present study demonstrates the potential of direct incorporation of DM with thermoplastics for 3D printing of patient-specific scaffolds for osteochondral regeneration.

3D-Printed PCL Scaffolds Combined with Juglone for Skin Tissue Engineering

Skin diseases are commonly treated with antihistamines, antibiotics, laser therapy, topical medications, local vitamins, or steroids. Since conventional treatments for wound healing (skin allografts, amnion, xenografts, etc.) have disadvantages such as antigenicity of the donor tissue, risk of infection, or lack of basement membrane, skin tissue engineering has become a popular new approach. The current study presents the design and fabrication of a new wound-dressing material by the addition of Juglone (5-hydroxy-1,4-naphthoquinone) to a 25% Polycaprolactone (PCL) scaffold. Juglone (J) is a significant allelochemical found in walnut trees and, in this study is used as a bioactive material. The effects of different amounts of J (1.25, 2.5, 5, 7.5, and 10 mg) on the biocompatibility, mechanical, chemical, thermal, morphological, and antimicrobial properties of the 3D-printed 25% PCL scaffolds were investigated. The addition of J increased the pore diameter of the 25% PCL scaffold. The maximum pore size (290.72 ± 14 µm) was observed for the highest amount of J (10 mg). The biocompatibility tests on the scaffolds demonstrated biocompatible behavior from the first day of incubation, the 25% PCL/7.5 J scaffold having the highest viability value (118%) among all of the J-loaded scaffolds. Drug release of J into phosphate buffered saline (PBS) at pH 7.4 showed that J was completely released from all 25% PCL/J scaffolds within 7 days of incubation.

Assessing the response of human primary macrophages to defined fibrous architectures fabricated by melt electrowriting.

The dual role of macrophages in the healing process depends on macrophage ability to polarize into phenotypes that can propagate inflammation or exert anti-inflammatory and tissue-remodeling functions. Controlling scaffold geometry has been proposed as a strategy to influence macrophage behavior and favor the positive host response to implants. Here, we fabricated Polycaprolactone (PCL) scaffolds by Melt Electrowriting (MEW) to investigate the ability of scaffold architecture to modulate macrophage polarization.Primary human macrophages unpolarized (M0) or polarized into M1, M2a, and M2c phenotypes were cultured on PCL films and MEW scaffolds with pore geometries (square, triangle, and rhombus grid) characterized by different angles.M0, M2a, and M2c macrophages wrapped along the fibers, while M1 macrophages formed clusters with rounded cells. Cell bridges were formed only for angles up to 90°. No relevant differences were found among PCL films and 3D scaffolds in terms of surface markers. CD206 and CD163 were highly expressed by M2a and M2c macrophages, with M2a macrophages presenting also high levels of CD86. M1 macrophages expressed moderate levels of all markers. The rhombus architecture promoted an increased release by M2a macrophages of IL10, IL13, and sCD163 compared to PCL films. The proangiogenic factor IL18 was also upregulated by the rhombus configuration in M0 and M2a macrophages compared to PCL films.The interesting findings obtained for the rhombus architecture represent a starting point for the design of scaffolds able to modulate macrophage phenotype, prompting investigations addressed to verify their ability to facilitate the healing process in vivo.

Cartilage regeneration using improved surface electrospun bilayer polycaprolactone scaffolds loaded with transforming growth factor-beta 3 and rabbit muscle-derived stem cells.

Polycaprolactone (PCL) has recently received significant attention due to its mechanical strength, low immunogenicity, elasticity, and biodegradability. Therefore, it is perfectly suitable for cartilage tissue engineering. PCL is relatively hydrophobic in nature, so its hydrophilicity needs to be enhanced before its use in scaffolding. In our study, first, we aimed to improve the hydrophilicity properties after the network of the bilayer scaffold was formed by electrospinning. Electrospun bilayer PCL scaffolds were treated with ozone and further loaded with transforming growth factor-beta 3 (TGFβ3). In vitro studies were performed to determine the rabbit muscle-derived stem cells’ (rMDSCs) potential to differentiate into chondrocytes after the cells were seeded onto the scaffolds. Statistically significant results indicated that ozonated (O) scaffolds create a better environment for rMDSCs because collagen-II (Coll2) concentrations at day 21 were higher than non-ozonated (NO) scaffolds. In in vivo studies, we aimed to determine the cartilage regeneration outcomes by macroscopical and microscopical/histological evaluations at 3- and 6-month time-points. The Oswestry Arthroscopy Score (OAS) was the highest at both mentioned time-points using the scaffold loaded with TGFβ3 and rMDSCs. Evaluation of cartilage electromechanical quantitative parameters (QPs) showed significantly better results in cell-treated scaffolds at both 3 and 6 months. Safranin O staining indicated similar results as in macroscopical evaluations—cell-treated scaffolds revealed greater staining with safranin, although an empty defect also showed better results than non-cell-treated scaffolds. The scaffold with chondrocytes represented the best score when the scaffolds were evaluated with the Mankin histological grading scale. However, as in previous in vivo evaluations, cell-treated scaffolds showed better results than non-cell-treated scaffolds. In conclusion, we have investigated that an ozone-treated scaffold containing TGFβ3 with rMDSC is a proper combination and could be a promising scaffold for cartilage regeneration.

Three-Dimensional Printing of Customized Scaffolds with Polycaprolactone-Silk Fibroin Composites and Integration of Gingival Tissue-Derived Stem Cells for Personalized Bone Therapy.

Regenerative biomaterials play a crucial role in the success of maxillofacial reconstructive procedures. Yet today, limited options are available when choosing polymeric biomaterials to treat critical size bony defects. Further, there is a requirement for 3D printable regenerative biomaterials to fabricate customized structures confined to the defect site. We present here a 3D printable composite formulation consisting of polycaprolactone (PCL) and silk fibroin microfibers and have established a robust protocol for fabricating customized 3D structures of complex geometry with the composite. The 3D printed composite scaffolds demonstrated higher compressive modulus than 3D printed scaffolds of PCL alone. Furthermore, the compressive modulus of PCL-Antheraea mylitta (AM) silk scaffolds is higher than that of the PCL-Bombyx mori (BM) silk scaffolds at their respective ratios. Compressive modulus of PCL-25AM silk scaffolds (73.4 MPa) is higher than that of PCL-25BM silk scaffolds (65.1 MPa). Compressive modulus of PCL-40AM silk scaffolds (106.1 MPa) is higher than that of PCL-40BM silk scaffolds (77.7 MPa). Moreover, we have isolated, characterized, and integrated human gingival mesenchymal stem cells (hGMSCs), an effective autologous cell source, onto the 3D printed scaffolds to evaluate their bone regeneration potential. The results demonstrated that PCL-silk microfiber composite scaffolds of Antheraea mylitta origin showed much higher bioactivity than the Bombyx mori ones because of arginine-glycine-aspartic acid (RGD) sequences present in the Antheraea mylitta silk fibroin protein favoring cell attachment and proliferation. By day 14, the metabolic activity of hGMSCs was highest in PCL-40AM (4.5 times higher than that at day 1). In addition, to show the translational potential of this work, we have fabricated a patient defect-specific model (mandible) using the CT scan obtained by the micro-CT imaging to understand the printability of the composite for fabricating complex structures to restore maxillofacial bony defects with precision when applied in a clinical scenario.

In Vivo Evaluation of PCL Vascular Grafts Implanted in Rat Abdominal Aorta.

Electrospun tissue-engineered grafts made of biodegradable materials have become a perspective search field in terms of vascular replacement, and more research is required to describe their in vivo transformation. This study aimed to give a detailed observation of hemodynamic and structural properties of electrospun, monolayered poly-ε-caprolactone (PCL) grafts in an in vivo experiment using a rat aorta replacement model at 10, 30, 60 and 90 implantation days. It was shown using ultrasound diagnostic and X-ray tomography that PCL grafts maintain patency throughout the entire follow-up period, without stenosis or thrombosis. Vascular compliance, assessed by the resistance index (RI), remains at the stable level from the 10th to the 90th day. A histological study using hematoxylin-eosin (H&E), von Kossa and Russell–Movat pentachrome staining demonstrated the dynamics of tissue response to the implant. By the 10th day, an endothelial monolayer was forming on the graft luminal surface, followed by the gradual growth and compaction of the neointima up to the 90th day. The intense inflammatory cellular reaction observed on the 10th day in the thickness of the scaffold was changed by the fibroblast and myofibroblast penetration by the 30th day. The cellularity maximum was reached on the 60th day, but by the 90th day the cellularity significantly (p = 0.02) decreased. From the 60th day, in some samples, the calcium phosphate depositions were revealed at the scaffold-neointima interface. Scanning electron microscopy showed that the scaffolds retained their fibrillar structure up to the 90th day. Thus, we have shown that the advantages of PCL scaffolds are excellent endothelialization and good surgical outcome. The disadvantages include their slow biodegradation, ineffective cellularization, and risks for mineralization and intimal hyperplasia.

Polycaprolactone scaffolds as a biomaterial for cementoblast delivery: An in vitro study.

To define the potential of polycaprolactone (PCL) scaffold for cementoblast delivery. Dental cementum is critical for tooth attachment and position, and its regenerative capabilities remain unpredictable. PCL scaffolds were manufactured by the electrospinning technique at 10% and 20% (w/v) and seeded with cementoblasts (OCCM-30). Scaffolds were characterized for their morphology and biological performance by scanning electron microscopy (SEM), confocal and conventional histology, cytocompatibility (PrestoBlue assay), gene expression (type I collagen - Col1; bone sialoprotein - Bsp; runt-related transcription factor 2 - Runx-2; alkaline phosphatase - Alpl; osteopontin - Opn; osteocalcin - Ocn, osterix - Osx), and the potential to induce extracellular matrix deposition and mineralization in vitro. Overall, data analysis showed that PCL scaffolds allowed cell adhesion and proliferation, modulated the expression of key markers of cementoblasts, and led to enhanced extracellular matrix deposition and calcium deposition as compared to the control group. Altogether, our findings allow concluding that PCL scaffolds are a viable tool to culture OCCM-30 cells, leading to an increased potential to promote mineralization in vitro. Further studies should be designed in order to define the clinical relevance of cementoblast-loaded PCL scaffolds to promote new cementum formation.

Hydrothermal synthesis of hydroxyapatite nanorods and their use in PCL bone scaffold

It is urgently needed to synthesize hydroxyapatite (HAP) nanorods with controllable size to mimic the morphology and size of natural human bone mineral for bone regeneration. In this study, HAP nanorods with size closed to natural human bone mineral were synthesized via hydrothermal method by changing hydrothermal temperature. Then they were introduced into biopolymer polycaprolactone (PCL) scaffold fabricated by selective laser sintering (SLS) to enhance its properties. The results revealed that the lower hydrothermal temperature was more favorable for HAP crystals to grow along c-axis at the length direction, while the increase in temperature was more favorable for the crystal to grow along a-axis at the width direction. The well-crystallized HAP nanorods obtained by hydrothermal method at 160 °C for 8 h had a diameter of 30 nm and a length of 200 nm. The introduction of 10 wt% HAP nanorods into PCL scaffold enhanced the tensile strength and compressive strength by 98.38% and 127.60% than the PCL scaffold. Meanwhile, the PCL/10%HAP scaffold could induce the deposition of apatites with a Ca/P ratio of 1.67 on its surface, which implied that the scaffold possessed excellent bioactivity. Besides, the scaffold exhibited good biocompatibility for cell attachment, spreading and proliferation.

3D bioprinting in airway reconstructive surgery: A pilot study

ObjectivesOpen surgery is a reliable choice for congenital subglottic stenosis, that represents the third most common congenital anomaly of the larynx. One of the procedures performed is anterior laryngotracheal reconstruction (LTR) with anterior rib graft. The objective of this preliminary study was to evaluate the potential of 3D printing technology for the realization of laryngo-tracheal scaffold in Polycaprolactone (PCL) implanted in vivo in ovine animal model. MethodsA 3D computer model of a laryngeal graft and a tracheal graft was designed and printed with PCL through 3D additive manufacturing technology. The scaffolds were seeded with autologous mesenchymal stem cells and cultured in vitro for up to 14 days. Anterior graft LTR with 3D printed scaffolds was performed on 5 sheep. The animals underwent endoscopic examinations at the first, 3rd, 6th, and 12th weeks after surgery and before sacrifice. The integration of the material was evaluated by the pathologist. ResultsTwo animals showed a favourable postoperative course and were sacrificed at 6 months postoperatively. In these cases, we observed endoscopically a complete integration of the cellularized PCL scaffold into the peri-implant tissues, and the pathologist found the growth of respiratory epithelium on the scaffold's inner surface. Other two animals showed a difficult post-operative recovery characterized by respiratory distress resulting in early sacrifice on postoperative days 31 and 33. In these animals we found a poor integration of the grafts into the tracheal structure, and a better integration of the laryngeal scaffold. The last animal developed a wound abscess and was sacrificed 80 days after surgery. We observed, in this case, a poor scaffold integration and an acute inflammatory reaction. ConclusionsFrom the preliminary data obtained we found that the excessive stiffness of the material, along with the anatomical features of the sheep, is a major limitation of this study. It will be necessary in the future to create a new biocompatible, more flexible and elastic graft, to achieve greater integration into surrounding tissues. Bioconstructed grafts could simplify surgery for the treatment of laryngo-tracheal stenosis, particularly in the treatment of long tracheal stenoses, which have, at the moment, very complex surgical options. Level of evidenceNA.

3D printed MXene (Ti2AlN)/polycaprolactone composite scaffolds for in situ maxillofacial bone defect repair

Obtaining a safe and reliable scaffold that can be rapidly fabricated and used for clinical bone defect repair has always been a challenge. In this study, polycaprolactone (PCL) composite scaffolds with various MXene (Ti2AlN) contents were prepared using 3D printing technology. The effects of different contents of Ti2AlN on the mechanical properties, hydrophilicity, cytocompatibility, and osteogenic differentiation ability were systematically studied and analysed. In vitro experiments showed that scaffolds containing 5% Ti2AlN (PCL@5#Ti2AlN) obtained the best cell adhesion and proliferation ability and significantly upregulated the alkaline phosphatase (ALP) level. In vivo experiments of tibial defect repair in rats showed that the PCL scaffold containing 5% Ti2AlN (PCL@5#Ti2AlN) could significantly promote the formation of new bone, and the experimental results of rabbit maxillofacial bone defect repair further proved that the PCL@5#Ti2AlN scaffold could effectively promote the repair of bone defects. Transcriptome analysis indicated that Ti2AlN may promote osteogenic differentiation by the Wnt/β-catenin signaling pathway and calcium-binding proteins. These findings suggest that Ti2AlN/PCL composite scaffolds with improved in situ bone repair ability represent an intelligent strategy for bone defect repair.

Functionalized 3D-Printed ST2/Gelatin Methacryloyl/Polcaprolactone Scaffolds for Enhancing Bone Regeneration with Vascularization.

Growth factors were often used to improve the bioactivity of biomaterials in order to fabricate biofunctionalized bone grafts for bone defect repair. However, supraphysiological concentrations of growth factors for improving bioactivity could lead to serious side effects, such as ectopic bone formation, radiculitis, swelling of soft tissue in the neck, etc. Therefore, safely and effectively applying growth factors in bone repair biomaterials comes to be an urgent problem that needs to be addressed. In this study, an appropriate concentration (50 ng/mL) of Wnt3a was used to pretreat the 3D-bioprinting gelatin methacryloyl(GelMA)/polycaprolactone(PCL) scaffold loaded with bone marrow stromal cell line ST2 for 24 h. This pretreatment promoted the cell proliferation, osteogenic differentiation, and mineralization of ST2 in the scaffold in vitro, and enhanced angiogenesis and osteogenesis after being implanted in critical-sized mouse calvarial defects. On the contrary, the inhibition of Wnt/β-catenin signaling in ST2 cells reduced the bone repair effect of this scaffold. These results suggested that ST2/GelMA/PCL scaffolds pretreated with an appropriate concentration of Wnt3a in culture medium could effectively enhance the osteogenic and angiogenic activity of bone repair biomaterials both in vitro and in vivo. Moreover, it would avoid the side effects caused by the supraphysiological concentrations of growth factors. This functionalized scaffold with osteogenic and angiogenic activity might be used as an outstanding bone substitute for bone regeneration and repair.

Effect of addition of Layered Double Hydroxides (LDH) on mechanical and biological properties of electrospun polycaprolactone scaffold

Effect of addition of Layered Double Hydroxides (LDH) on mechanical and biological properties of electrospun polycaprolactone scaffold