3D Bioplotter Research Papers
Co-culture bioprinting of tissue-engineered bone-periosteum biphasic complex for repairing critical-sized skull defects in rabbits
Tissue engineering based on bioprinting technology has broad prospects in the treatment of critical-sized bone defect. Nevertheless, it is challenging to construct composite tissues or organs with structural integrity. Periosteum and stem cells are important in bone regeneration, and it has been shown that co-culture engineering system could successfully repair bone defects. Here, a strategy of co-culture bioprinting was proposed, and a tissue-engineered bone-periosteum biphasic complex was designed. Poly-L-lactic acid/hydroxyapatite (PLLA/HA) was used to construct the supporting scaffold of bone phase. Gelatin methacryl (GelMA) loaded with rabbit bone mesenchymal stem cells (BMSCs) and periosteum-derived stem cells (PDSCs) were used to…
A 3D-printed PCL/PEI/DNA bioactive scaffold for chemotherapy drug capture in vivo
Systemic chemotherapy after surgery is necessary to control tumor recurrence, but the severe side effects caused by chemotherapeutic drugs pose a great threat to patients’ health. In this study, we originally develop a porous scaffold used for chemotherapy drug capture by using 3D printing technology. The scaffold is mainly composed of poly (ε-caprolactone) (PCL) and polyetherimide (PEI) with a mass ratio of 5/1. Subsequently, the printed scaffold is modified with DNA through the strong electrostatic integration between DNA and PEI to endow the scaffold with the specific absorption to doxorubicin (DOX, a widely used chemotherapy drug). The results show that…
Dual-functional 3D-printed composite scaffold for inhibiting bacterial infection and promoting bone regeneration in infected bone defect models
Infection is one of the pivotal causes of nonunion in large bone defect after trauma or tumor resection. Three-dimensional (3D) composite scaffold with multifunctional-therapeutic properties offer many advantages over allogenic or xenogenic bone grafting for the restoration of challenging infected bone defects. In the previous study, we demonstrated that quaternized chitosan (HACC)-grafted polylactide-co-glycolide (PLGA)/hydroxyapatite (HA) scaffold (PLGA/HA/HACC) via 3D-printing technique exhibited significantly improved antimicrobial and osteoconductive property in vitro, together with good biocompatibility in vivo. Hence, the present study further investigated whether such an innovative bone substitute could effectively inhibit the bacterial biofilm formation and promote bone regeneration in vivo.…
3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration
Although several bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules for enhanced bone regeneration have been recently developed, the manipulation of on-demand release profiles of different biomolecules during bone regeneration remains challenging. Herein, a 3D-printed dual-drug-loaded biomimetic scaffold to regulate the host stem cell recruitment and osteogenic differentiation in a two-stage process for bone regeneration was successfully fabricated. First, a chemotactic small-molecule drug, namely, simvastatin (SIM) was directly incorporated into the hydroxyapatite/collagen bioink for printing and could be rapidly released during the early stage of bone regeneration. Further, near-infrared (NIR)-light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the…
Synergistic effects of calcium silicate/zinc silicate dual compounds and in-situ interconnected pores on promoting bone regeneration of composite scaffolds
Rapid bone regeneration in implants is important for successful transplantation. In this regard, we report the development of calcium silicate/zinc silicate (CS/ZS) dual-compound-incorporated calcium phosphate cement (CPC) scaffolds with a three-dimensional poly (lactic-co-glycolic acid) network that synergistically promote bone regeneration. In vitro results demonstrated that the incorporation of CS/ZS dual compounds into the CPC significantly promoted the osteogenic differentiation of stem cells compared to the addition of CS or ZS alone. Moreover, the bone-regeneration efficacy of the composite scaffolds was validated by filling in femur condyle defects in rabbits, which showed that the scaffolds with CS and ZS possessed a…
Self-setting calcium phosphate cement scaffolds with pre-forming and in-situ forming interconnected macropores: Comparative study in vitro and in vivo
Creating interconnected macropores in calcium phosphate cement (CPC) is an effective strategy to promote its degradation and osteogenesis. However, little attention has been given to the osteogenic effect of the CPC scaffolds with pre-forming and in-situ forming interconnected macropores. Herein, two types of CPC scaffolds were prepared by infiltrating CPC pastes into 3D-printed polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) networks. Meanwhile, the sacrificial PCL network within CPC was dissolved to obtain the CPC scaffold with approximately 300 μm macropores, whereas the PLGA network was retained within the CPC to obtain the PLGA/CPC scaffold. The results indicated that the PLGA/CPC scaffold…
3D printed PLGA scaffold with nano-hydroxyapatite carrying linezolid for treatment of infected bone defects
Background Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD). Methods PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone…
Correlation between Ca Release and Osteoconduction by 3D-Printed Hydroxyapatite-Based Templates
The application of hydroxyapatite (HA)-based templates is quite often seen in bone tissue engineering since that HA is an osteoconductive bioceramic material, which mimics the inorganic component of mineralized tissues. However, the reported osteoconductivity varies in vitro and in vivo, and the levels of calcium (Ca) release most favorable to osteoconduction have yet to be determined. In this study, HA-based templates were fabricated by melt-extrusion 3D-printing and characterized in order to determine a possible correlation between Ca release and osteoconduction. The HA-based templates were blended with poly(lactide-co-trimethylene carbonate) (PLATMC) at three different HA ratios: 10, 30, and 50%. The printability…
Silk fibroin/polyacrylamide-based tough 3D printing scaffold with strain sensing ability and chondrogenic activity
Cartilage tissue plays an important role in our life activities. The poor self-repair capacity makes cartilage tissue engineering an urgent clinical demand. Among them, the development of tissue engineering scaffolds with both biomimetic features and microenvironment signal sensing abilities could significantly promote the development of cartilage tissue engineering. While most of the reported cartilage scaffolds have no intelligent sensing features. Herein, a ternary composite 3D printing scaffold with both strain sensing ability and desired mechanical property was developed, by using regenerated silk fibroin (RSF) and polyacrylamide (PAM) as main matrixes, and oxidized bacterial cellulose nanofibers (OBC) as filler. Then, the…
Three-Dimensional Bioprinting of a Structure-, Composition-, and Mechanics-Graded Biomimetic Scaffold Coated with Specific Decellularized Extracellular Matrix to Improve the Tendon-to-Bone Healing
Healing of a damaged tendon-to-bone enthesis occurs through the formation of fibrovascular scar tissue with greatly compromised histological and biomechanical properties instead of the regeneration of a new enthesis due to the lack of graded tissue-engineering zones in the interface during the healing process. In the present study, a structure-, composition-, and mechanics-graded biomimetic scaffold (GBS) coated with specific decellularized extracellular matrix (dECM) (GBS-E) aimed to enhance its cellular differentiation inducibilities was fabricated using a three-dimensional (3-D) bioprinting technique. In vitro cellular differentiation studies showed that from the tendon-engineering zone to the bone-engineering zone in the GBS, the tenogenic differentiation…
Meniscal fibrocartilage regeneration inspired by meniscal maturational and regenerative process
Meniscus is a complex and crucial fibrocartilaginous tissue within the knee joint. Meniscal regeneration remains to be a scientific and translational challenge. We clarified that mesenchymal stem cells (MSCs) participated in meniscal maturation and regeneration using MSC-tracing transgenic mice model. Here, inspired by meniscal natural maturational and regenerative process, we developed an effective and translational strategy to facilitate meniscal regeneration by three-dimensionally printing biomimetic meniscal scaffold combining autologous synovium transplant, which contained abundant intrinsic MSCs. We verified that this facilitated anisotropic meniscus–like tissue regeneration and protected cartilage from degeneration in large animal model. Mechanistically, the biomechanics and matrix stiffness up-regulated…
Enhanced osteochondral repair with hyaline cartilage formation using an extracellular matrix-inspired natural scaffold
Osteochondral defects pose a great challenge and a satisfactory strategy for their repair has yet to be identified. In particular, poor repair could result in the generation of fibrous cartilage and subchondral bone, causing the degeneration of osteochondral tissue and eventually leading to repair failure. Herein, taking inspiration from the chemical elements inherent in the natural extracellular matrix (ECM), we proposed a novel ECM-mimicking scaffold composed of natural polysaccharides and polypeptides for osteochondral repair. By meticulously modifying natural biopolymers to form reversible guest–host and rigid covalent networks, the scaffold not only exhibited outstanding biocompatibility, cell adaptability, and biodegradability, but also…
Augmented Repair and Regeneration of Critical Size Rabbit Calvaria Defects with 3D Printed Silk Fibroin Microfibers Reinforced PCL Composite Scaffolds
Treatment of critical size defects is quite challenging, often requiring autologous bone grafts for bone regeneration. A massive volume of autologous bone is essential during this process to fill the defect leading to donor site morbidity. Although 3D printed PCL scaffolds are frequently utilised for bone correction procedures, there have been reports of delayed PCL biodegradation and inadequate bone tissue formation. To enhance the regenerative potential, in this study, silk in the form of silk fibroin microfibers are reinforced into the PCL matrix to form the composite. Two silk variations were used: Antheraea mylitta and Bombyx mori, and has been…
Loose Pre-Cross-Linking Mediating Cellulose Self-Assembly for 3D Printing Strong and Tough Biomimetic Scaffolds
The lack of an effective printable ink preparation method and the usual mechanically weak performance obstruct the functional 3D printing hydrogel exploitation and application. Herein, we propose a gentle pre-cross-linking strategy to enable a loosely cross-linked cellulose network for simultaneously achieving favorable printability and a strong hydrogel network via mediating the cellulose self-assembly. A small amount of epichlorohydrin is applied to (i) slightly pre-cross-link the cellulose chains for forming the percolating network to regulate the rheological properties and (ii) form the loosely cross-linked points to mediate the cellulose chains’ self-assembly for achieving superior mechanical properties. The fabrication of the complex…
3D-printed regenerative polycaprolactone/silk fibroin osteogenic and chondrogenic implant for treatment of hip dysplasia
Hip dysplasia is a developmental disorder that resulted in insufficient acetabular coverage. Current surgical treatments are technically demanding, complex, invasive, and often lead to associated complications. Therefore, the development of regenerative implants that fit to the bone and induce osteogenesis and chondrogenesis is in high demand. In this study, an implant was developed in which the osteogenic part was 3D printed using polycaprolactone (PCL), crosslinked with dopamine, and subjected to surface mineralization; while the chondrogenic part was prepared using silk fibroin (SF) and bone morphogenetic protein 2. Physical and chemical characterization of the implant was conducted using energy dispersive spectrometry…
3D bioprinting of multilayered scaffolds with spatially differentiated ADMSCs for rotator cuff tendon-to-bone interface regeneration
Regeneration of the gradient structure of the tendon-to-bone interface is still a significant clinical challenge. This study reports a novel therapeutic method combining three-dimensional (3D) bioprinting and melt electrospinning writing techniques to regenerate a functional tendon-to-bone interface. We generated biomimetic multilayered scaffolds with 3D-bioprinted pre-differentiated autologous adipose-derived mesenchymal stem cells (ADMSC), which recapitulated compositional and cellular structures of the interface. The hydrogel-based bioinks offered high cell viability and proliferative capability for rabbit ADMSCs. The hydrogels with pre-differentiated (into tenogenic, chondrogenic, and osteogenic lineages) or undifferentiated rabbit ADMSCs were 3D-bioprinted into zonal-specific constructs to mimic the structure of the tendon-to-bone interface.…
3D-printed composite scaffold with anti-infection and osteogenesis potential against infected bone defects
In the field of orthopedics, an infected bone defect is a refractory disease accompanied by bone infection and defects as well as aggravated circulation. There are currently no personalized scaffolds that can treat bone infections using local stable and sustained-release antibiotics while providing mechanical support and bone induction to promote bone repair in the process of absorption in vivo. In our previous study, rifampicin/moxifloxacin-poly lactic-co-glycolic acid (PLGA) microspheres were prepared and tested for sustained release and antibacterial activity. The composite scaffold of poly-L-lactic acid (PLLA)/Pearl had a positive effect on mechanics supports and promoted osteogenesis. Therefore, in this study, the…
Contact osteogenesis by biodegradable 3D-printed poly(lactide-co-trimethylene carbonate)
Background To support bone regeneration, 3D-printed templates function as temporary guides. The preferred materials are synthetic polymers, due to their ease of processing and biological inertness. Poly(lactide-co-trimethylene carbonate) (PLATMC) has good biological compatibility and currently used in soft tissue regeneration. The aim of this study was to evaluate the osteoconductivity of 3D-printed PLATMC templates for bone tissue engineering, in comparison with the widely used 3D-printed polycaprolactone (PCL) templates. Methods The printability and physical properties of 3D-printed templates were assessed, including wettability, tensile properties and the degradation profile. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were used to evaluate osteoconductivity and…
Solvent Mediating the in Situ Self-Assembly of Polysaccharides for 3D Printing Biomimetic Tissue Scaffolds
Intensively studied 3D printing technology is frequently hindered by the effective printable ink preparation method. Herein, we propose an elegant and gentle solvent consumption strategy to slowly disrupt the thermodynamic stability of the biopolymer (polysaccharide: cellulose, chitin, and chitosan) solution to slightly induce the molecule chains to in situ self-assemble into nanostructures for regulating the rheological properties, eventually achieving the acceptable printability. The polysaccharides are dissolved in the alkali/urea solvent. The weak Lewis acid fumed silica (as solvent mediator) is used to (i) slowly and partially consume the alkali/urea solvent to induce the polysaccharide chains to self-assemble into nanofibers to…
Three-Dimensional Printing of Calcium Carbonate/Hydroxyapatite Scaffolds at Low Temperature for Bone Tissue Engineering
Three-dimensional (3D) printing technology has been applied to fabricate bone tissue engineering scaffolds for a wide range of materials with precisely control over scaffold structures. Coral is a potential bone repair and bone replacement material. Due to the natural source limitation of coral, we developed a fabrication protocol for 3D printing of calcium carbonate (CaCO3) nanoparticles for coral replacement in the application of bone tissue engineering. Up to 80% of CaCO3 nanoparticles can be printed with high resolution using poly-l-lactide as a blender. The scaffolds were subjected to a controlled hydrothermal process for incomplete conversion of carbonate to phosphate to…
The effect of enhanced bone marrow in conjunction with 3D-printed PLA-HA in the repair of critical-sized bone defects in a rabbit model
Background: Traditionally, the iliac crest has been the most common harvesting site for autologous bone grafts; however, it has some limitations, including poor bone availability and donor-site morbidity. This study sought to explore the effect of enhanced bone marrow (eBM) in conjunction with three-dimensional (3D)-printed polylactide–hydroxyapatite (PLA-HA) scaffolds in the repair of critical-sized bone defects in a rabbit model. Methods: First, 3D-printed PLA-HA scaffolds were fabricated and evaluated using micro-computed tomography (µCT) and scanning electron microscopy (SEM). Twenty-seven New Zealand white rabbits were randomly divided into 3 groups (n=9 per group), and the defects were treated using 3D-printed PLA-HA scaffolds…
The effect of induced membranes combined with enhanced bone marrow and 3D PLA-HA on repairing long bone defects in vivo
The repair of large bone defects has always been a challenge, especially with respect to regeneration capacity and autogenous bone availability. To address this problem, we fabricated a 3D-printed polylactic acid (PLA) and hydroxyapatite (HA) scaffold (3D-printed PLA-HA, providing scaffold) loaded with enhanced bone marrow (eBM, providing seed cells) combined with induced membrane (IM, providing grow factors) to repair large radial defects in rabbits. in vitro assays, we demonstrated that 3D-printed PLA-HA had excellent biocompatibility, as shown by co-culturing with mesenchymal stem cells (MSCs); eBM-derived MSCs exhibited considerable differentiation potential, as shown in trilineage differentiation assays. To investigate bone formation…
3D printed silk-gelatin hydrogel scaffold with different porous structure and cell seeding strategy for cartilage regeneration
Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics. However, most hydrogels offer limited cell growth and tissue formation ability due to their submicron- or nano-sized gel networks, which restrict the supply of oxygen, nutrients and inhibit the proliferation and differentiation of encapsulated cells. In recent years, 3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds. In this study, we fabricated a macroporous hydrogel scaffold through horseradish peroxidase (HRP)-mediated crosslinking of silk fibroin (SF) and tyramine-substituted gelatin (GT) by extrusion-based low-temperature 3D printing. Through physicochemical characterization,…
Functional reconstruction of injured corpus cavernosa using 3D-printed hydrogel scaffolds seeded with HIF-1α-expressing stem cells
Injury of corpus cavernosa results in erectile dysfunction, but its treatment has been very difficult. Here we construct heparin-coated 3D-printed hydrogel scaffolds seeded with hypoxia inducible factor-1α (HIF-1α)-mutated muscle-derived stem cells (MDSCs) to develop bioengineered vascularized corpora. HIF-1α-mutated MDSCs significantly secrete various angiogenic factors in MDSCs regardless of hypoxia or normoxia. The biodegradable scaffolds, along with MDSCs, are implanted into corpus cavernosa defects in a rabbit model to show good histocompatibility with no immunological rejection, support vascularized tissue ingrowth, and promote neovascularisation to repair the defects. Evaluation of morphology, intracavernosal pressure, elasticity and shrinkage of repaired cavernous tissue prove that…
Biomechanically, structurally and functionally meticulously tailored polycaprolactone/silk fibroin scaffold for meniscus regeneration
Meniscus deficiency, the most common and refractory disease in human knee joints, often progresses to osteoarthritis (OA) due to abnormal biomechanical distribution and articular cartilage abrasion. However, due to its anisotropic spatial architecture, complex biomechanical microenvironment, and limited vascularity, meniscus repair remains a challenge for clinicians and researchers worldwide. In this study, we developed a 3D printing-based biomimetic and composite tissue-engineered meniscus scaffold consisting of polycaprolactone (PCL)/silk fibroin (SF) with extraordinary biomechanical properties and biocompatibility. We hypothesized that the meticulously tailored composite scaffold could enhance meniscus regeneration and cartilage protection. Methods: The physical property of the scaffold was characterized by…
Heparan sulfate loaded polycaprolactone-hydroxyapatite scaffolds with 3D printing for bone defect repair
With the increasing applications of 3D printing technology in biomedical field, the composition or additives of the related materials has become critical for the next development. In the current study, we have prepared 3D printed polycaprolactone-hydroxyapatite (PCL-HA) porous scaffolds with loaded heparan sulfate (HS), in order to reveal the reparative effect of different concentrations of HS on the healing of bone defects. As a result, the scaffold itself showed sound compression resistance, air porosity and good biocompatibility. From both in vitro and in vivo experiments, the scaffold with low concentration of HS led to positive effects in promoting osteoblast maturation…
The application of BMP-12-overexpressing mesenchymal stem cells loaded 3D-printed PLGA scaffolds in rabbit rotator cuff repair
This study investigates if the application of bone marrow-derived mesenchymal stem cells (BM-MSCs) loaded 3D-printed scaffolds could improve rotator cuff repair. The polylactic-co-glycolic acid (PLGA) scaffolds were fabricated by 3D print technology. Rabbit BM-MSCs were transfected with a recombinant adenovirus encoding bone morphogenic protein 12 (BMP-12). The effect of BM-MSCs loaded PLGA scaffolds on tendon-bone healing was assessed by biomechanical testing and histological analysis in a rabbit rotator cuff repair model. We found that the PLGA scaffolds had good biocompatible and biodegradable property. Overexpression of BMP-12 increased the mRNA and protein expression of tenogenic genes in BM-MSCs cultured with DMEM…
Novel Strategy to Accelerate Bone Regeneration of Calcium Phosphate Cement by Incorporating 3D Plotted Poly(lactic‐co‐glycolic acid) Network and Bioactive Wollastonite
Inefficient bone regeneration of self‐hardening calcium phosphate cement (CPC) increases the demand for interconnected macropores and osteogenesis‐stimulated substances. It remains a challenge to fabricate porous CPC with interconnected macropores while maintaining its advantages, such as plasticity. Herein, pastes containing CPC and wollastonite (WS) are infiltrated into a 3D plotted poly(lactic‐co‐glycolic acid) (PLGA) network to fabricate plastic CPC‐based composite cement (PLGA/WS/CPC). The PLGA/WS/CPC recovers the plasticity of CPC after being heated above the glass transition temperature of PLGA. The presence of the 3D PLGA network significantly increases the flexibility of CPC in prophase and generates 3D interconnected macropores in situ upon…
Bio-fabrication of peptide-modified alginate scaffolds: Printability, mechanical stability and neurite outgrowth assessments
Peripheral nerve tissue requires appropriate biochemical and physical cues to guide the regeneration process after injury. Bioprinted peptide-conjugated sodium alginate (PCSA) scaffolds have the potential to provide physical and biochemical cues simultaneously. Such scaffolds need characterisation in terms of printability, mechanical stability, and biological performance to refine and improve application in nerve tissue regeneration. In this study, it was hypothesized that 3D scaffold printed with low concentrated multiple PCSA precursor would be supportive for axon outgrowth. Therefore, a 2% (w/v) alginate precursor was conjugated with either arginine-glycine-aspartate (RGD) or tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptides, or a mixture of RGD and YIGSR (1:2)…
3D printed biofunctionalized scaffolds for microfracture repair of cartilage defects
While articular cartilage defects affect millions of people worldwide from adolescents to adults, the repair of articular cartilage defects still remains challenging due to the limited endogenous regeneration of the tissue and poor integration with implants. In this study, we developed a 3D-printed scaffold functionalized with aggrecan that supports the cellular fraction of bone marrow released from microfracture, a widely used clinical procedure, and demonstrated tremendous improvement of regenerated cartilage tissue quality and joint function in a lapine model. Optical coherence tomography (OCT) revealed doubled thickness of the regenerated cartilage tissue in the group treated with our aggrecan functionalized scaffold…
Zein regulating apatite mineralization, degradability, in vitro cells responses and in vivo osteogenesis of 3D-printed scaffold of n-MS/ZN/PCL ternary composite
Bioactive and degradable scaffolds of nano magnesium silicate (n-MS)/zein (ZN)/poly(caprolactone) (PCL) ternary composites were prepared by 3D-printing method. The results showed that the 3D-printed scaffolds possessed controllable pore structure, and pore morphology, pore size, porosity and pore interconnectivity of the scaffolds can be efficiently adjusted. In addition, the apatite-mineralization ability of the scaffolds in simulated body fluids was obviously improved with the increase of ZN content, in which the scaffold with 20 w% ZN (C20) possessed excellent apatite-mineralization ability. Moreover, the degradability of the scaffolds was significantly enhanced with the increase of ZN content in the scaffolds. The degradation of…
3D printing of pearl/CaSO4 composite scaffolds for bone regeneration
The development of biomaterials with high osteogenic ability for fast osteointegration with a host bone is of great interest. In this study, pearl/CaSO4 composite scaffolds were fabricated using three-dimensional (3D) printing, followed by a hydration process. The pearl/CaSO4 scaffolds showed uniform interconnected macropores (∼400 μm), high porosity (∼60%), and enhanced compressive strength. With CaSO4 scaffolds as a control, the biological properties of the pearl/CaSO4 scaffolds were evaluated in vitro and in vivo. The results showed that the pearl/CaSO4 scaffolds possessed a good apatite-forming ability and stimulated the proliferation and differentiation of rat bone mesenchymal stem cells (rBMSCs), as well as…
Micro-precise spatiotemporal delivery system embedded in 3D printing for complex tissue regeneration
Three dimensional (3D) printing has emerged as an efficient tool for tissue engineering and regenerative medicine, given its advantages for constructing custom-designed scaffolds with tunable microstructure/physical properties. Here we developed a micro-precise spatiotemporal delivery system embedded in 3D printed scaffolds. PLGA microspheres (μS) were encapsulated with growth factors (GFs) and then embedded inside PCL microfibers that constitute custom-designed 3D scaffolds. Given the substantial difference in the melting points between PLGA and PCL and their low heat conductivity, μS were able to maintain its original structure while protecting GF’s bioactivities. Micro-precise spatial control of multiple GFs was achieved by interchanging dispensing…
3D-printed hierarchical scaffold for localized isoniazid/rifampin drug delivery and osteoarticular tuberculosis therapy
After surgical treatment of osteoarticular tuberculosis (TB), it is necessary to fill the surgical defect with an implant, which combines the merits of osseous regeneration and local multi-drug therapy so as to avoid drug resistance and side effects. In this study, a 3D-printed macro/meso-porous composite scaffold is fabricated. High dosages of isoniazid (INH)/rifampin (RFP) anti-TB drugs are loaded into chemically modified mesoporous bioactive ceramics in advance, which are then bound with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) through a 3D printing procedure. The composite scaffolds show greatly prolonged drug release time compared to commercial calcium phosphate scaffolds either in vitro or in vivo.…
Three-dimensionally plotted MBG/PHBHHx composite scaffold for antitubercular drug delivery and tissue regeneration
A suitable drug-loaded scaffold that can postoperatively release an antituberculosis drug efficiently in a lesion area and help repair a bone defect is very important in the clinical treatment of bone tuberculosis (TB). In this study, a composite drug-loaded cylindrical scaffold was prepared by using three-dimensional printing technology in combination with the mesoporous confinement range, surface chemical groups, and gradual degradation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). This achieves the slow release of a drug for as long as possible. We implanted the drug-loaded compound scaffold into New Zealand rabbits’ femur defect model to study the in vivo drug release performance and osteogenic ability.…
The Application of Three-Dimensional Printing in Animal Model of Augmentation Rhinoplasty
The role of three-dimensional (3D) printing has expanded in diverse areas in medicine. As plastic surgery needs to fulfill the different demands from diverse individuals, the applications of tailored 3D printing will become indispensable. In this study, we evaluated the feasibility of using 3D-printed polycaprolactone (PCL) scaffold seeded with fibrin/chondrocytes as a new dorsal augmentation material for rhinoplasty. The construct was surgically implanted on the nasal dorsum in the subperiosteal plane of six rabbits. The implants were harvested 4 and 12 weeks after implantation and evaluated by gross morphological assessment, radiographic imaging, and histologic examination. The initial shape of the…
Tissue‐Engineered Tracheal Reconstruction Using Three‐Dimensionally Printed Artificial Tracheal Graft: Preliminary Report
Three-dimensional printing has come into the spotlight in the realm of tissue engineering. We intended to evaluate the plausibility of 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded and cultured. A half-pipe-shaped 3DP polycaprolactone scaffold was coated with the MSCs seeded in fibrin. The half-pipe tracheal graft was implanted on a 10 × 10-mm artificial tracheal defect in four rabbits. Four and eight weeks after the operation, the reconstructed sites were evaluated bronchoscopically, radiologically, histologically, and functionally. None of the four rabbits showed any…
In‐vivo behavior of Si‐hydroxyapatite/polycaprolactone/DMB scaffolds fabricated by 3D printing
Scaffolds made of polycaprolactone and nanocrystalline silicon-substituted hydroxyapatite have been fabricated by 3D printing rapid prototyping technique. To asses that the scaffolds fulfill the requirements to be considered for bone grafting applications, they were implanted in New Zealand rabbits. Histological and radiological studies have demonstrated that the scaffolds implanted in bone exhibited an excellent osteointegration without the interposition of fibrous tissue between bone and implants and without immune response after 4 months of implantation. In addition, we have evaluated the possibility of improving the scaffolds efficiency by incorporating demineralized bone matrix during the preparation by 3D printing. When demineralized bone…
A biomimetic growth factor delivery strategy for enhanced regeneration of iliac crest defects
The importance of provision of growth factors in the engineering of tissues has long been shown to control the behavior of the cells within the construct and several approaches were applied toward this end. In nature, more than one type of growth factor is known to be effective during the healing of tissue defects and their peak concentrations are not always simultaneous. One of the most recent strategies includes the delivery of a combination of growth factors with the dose and timing to mimic the natural regeneration cascade. The sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 which are…
Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study
Background A common approach for tissue regeneration is cell delivery, for example by direct transplantation of stem or progenitor cells. An alternative, by recruitment of endogenous cells, needs experimental evidence. We tested the hypothesis that the articular surface of the synovial joint can regenerate with a biological cue spatially embedded in an anatomically correct bioscaffold. Methods In this proof of concept study, the surface morphology of a rabbit proximal humeral joint was captured with laser scanning and reconstructed by computer-aided design. We fabricated an anatomically correct bioscaffold using a composite of poly-ɛ-caprolactone and hydroxyapatite. The entire articular surface of unilateral…
Rapid prototyping of anatomically shaped, tissue-engineered implants for restoring congruent articulating surfaces in small joints
Background: Preliminary studies investigated advanced scaffold design and tissue engineering approaches towards restoring congruent articulating surfaces in small joints. Materials and methods: Anatomical femoral and tibial cartilage constructs, fabricated by three-dimensional fibre deposition (3DF) or compression moulding/particulate leaching (CM), were evaluated in vitro and in vivo in an autologous rabbit model. Effects of scaffold pore architecture on rabbit chondrocyte differentiation and mechanical properties were evaluated following in vitro culture and subcutaneous implantation in nude mice. After femoral and tibial osteotomy and autologous implantation of tissue-engineered constructs in rabbit knee joints, implant fixation and joint articulation were evaluated. Results: Rapid prototyping…