3D-printed Scaffolds Research Articles

PLLA/(MWCNTs-ZnO)@PDA composite with NIR-light induced shape memory effect, antibacterial properties and 3D printability

PLLA based shape-memory polymer composites with multifunctions have attracted growing attention in biomedical applications. Generally, a single nanofiller has the problem of insufficient functionalization and easy aggregation. Therefore, we design and fabricate polydopamine (PDA) surface modified MWCNTs-ZnO hybrid nanostructure ((MWCNTs-ZnO)@PDA). The dispersion of (MWCNTs-ZnO)@PDA in PLLA is improved in comparison with the pristine MWCNTs or ZnO. The results indicate that the (MWCNTs-ZnO)@PDA nanosystem shows a synergistic effect on the mechanical properties and photothermal properties of the composites. Comparative analysis with neat PLLA demonstrates a remarkable 17% increase in tensile strength and a 19% increase in elongation at break for PLLA/(MWCNTs-ZnO)@PDA composite. Additionally, the composites exhibit excellent NIR light-induced shape memory effects with a shape recovery ratio reaching 100%. Moreover, PLLA/(MWCNTs-ZnO)@PDA composites show favorable antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, the polymer composites display good 3D printability, and the 3D-printed porous scaffold possesses high compressive strength and modulus. Also, the PLLA/(MCNTs-ZnO)@PDA scaffold can be compressed into a compact size and recover its original shape under NIR light irradiation. This work provides an approach to prepare novel shape-memory polymer composites with multifunctions including high strength, light-induced shape-recovery, antibacterial properties and printability.

3D-Printed Chitosan-Based Scaffolds with Scutellariae baicalensis Extract for Dental Applications.

The plant material Scutellariae baicalensis radix, which is rich in flavones (baicalin), possesses antibacterial, antifungal, antioxidant, and anti-inflammatory properties. This work aimed to develop a 3D-printed chitosan-based hydrogel rich in Scutellariae baicalensis extract as an innovative approach for the personalized treatment of periodontal diseases. Chitosan-based hydrogels were prepared, and the printability of the prepared hydrogels was determined. The hydrogel with 2.5% w/v of high molecular-weight chitosan (CS), 2% w/v gelatin (Gel), and 10% w/w of extract (Ex) presented the best printability, producing smooth and uniform scaffolds. It was proved that the CS/Gel/Ex hydrogel was stabilized by hydrogen bonds and remained in amorphous dispersion in the 3D-printed structures (confirmed by ATR-FTIR and XRPD). Due to the amorphization of the active substance, a significant increase in the release of baicalin in vitro was observed. It was demonstrated that there was an initial burst release and a continuous release profile (n = 3). Higuchi kinetic was the most likely baicalin release kinetic. The second fit, the Korsmeyer-Peppas kinetics model, showed coupled diffusion of the active ingredient in the hydrated matrix and polymer relaxation regulated release, with n values ranging from 0.45 to 0.89. The anti-inflammatory properties of 3D-printed scaffolds were assessed as the ability to inhibit the activity of the hyaluronidase enzyme. Activity was assessed as IC50 = 63.57 ± 4.98 mg hydrogel/mL (n = 6). Cytotoxicity tests demonstrated the biocompatibility of the material. After 24 h of exposure to the 2.5CS/2Gel/10Ex scaffold, fibroblasts migrated toward the scratch, closed the "wound" by 97.1%, and significantly accelerated the wound healing process. The results render the 3D-printed CS/Gel/extract scaffolds as potential candidates for treating periodontal diseases.

In vivo research on 3D-printed composite PLGA and PDLLA-HA absorbable scaffolds for repairing radius defects in rabbits.

Despite being an important research topic in oral biomaterials, few studies have demonstrated the differences between poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and poly(d,l-lactic acid)/hydroxyapatite (PDLLA/HA). In this study, PLGA/HA and PDLLA/HA scaffolds were prepared using three-dimensional (3D) printing technology and implanted into radius defects in rabbits to assess their effects on bone regeneration. In this study, 6 mm × 4 mm bone defects were generated in the bilateral radii of rabbits. 3D-printed PLGA/HA and PDLLA/HA scaffolds were implanted into the defects. X-ray imaging, micro-computed tomography, and hematoxylin-eosin staining were performed to observe the degradation of the materials, the presence of new bone, and bone remodeling in the bone defect area. The PLGA/HA scaffolds displayed complete degradation at 20 weeks, whereas PDLLA/HA scaffolds exhibited incomplete degradation. Active osteoblasts were detected in both groups. The formation of new bone, bone marrow cavity reconstruction, and cortical bone remodeling were better in the PLGA/HA group than in the PDLLA/HA group. PLGA/HA scaffolds performed better than PDLLA/HA scaffolds in repairing bone defects, making the former scaffolds more suitable as bone substitutes at the same high molecular weight.

Investigation of 3D Printed Bioresorbable Vascular Scaffold Crimping Behavior.

The rise in additive manufacturing (AM) offers myriad opportunities for 3D-printed polymeric vascular scaffolds, such as customization and on-the-spot manufacturing, in vivo biodegradation, incorporation of drugs to prevent restenosis, and visibility under X-ray. To maximize these benefits, informed scaffold design is critical. Polymeric bioresorbable vascular scaffolds (BVS) must undergo significant deformation prior to implantation in a diameter-reduction process known as crimping which enables minimally invasive surgery. Understanding the behavior of vascular scaffolds in this step provides twofold benefits: first, it ensures the BVS is able to accommodate stresses occurring during this process to prevent failure, and further, it provides information on the radial strength of the BVS, a key metric to understanding its post-implant performance in the artery. To capitalize on the fast manufacturing speed AM provides, a low time cost solution for understanding scaffold performance during this step is necessary. Through simulation of the BVS crimping process in ABAQUS using experimentally obtained bulk material properties, we have developed a qualitative analysis tool which is capable of accurately comparing relative performance trends of varying BVS designs during crimping in a fraction of the time of experimental testing, thereby assisting in the integration of informed design into the additive manufacturing process.

Fused Deposition Modeling 3D-Printed Scaffolds for Bone Tissue Engineering Applications: A Review.

The emergence of bone tissue engineering as a trend in regenerative medicine is forcing scientists to create highly functional materials and scaffold construction techniques. Bone tissue engineering uses 3D bio-printed scaffolds that allow and stimulate the attachment and proliferation of osteoinductive cells on their surfaces. Bone grafting is necessary to expedite the patient's condition because the natural healing process of bones is slow. Fused deposition modeling (FDM) is therefore suggested as a technique for the production process due to its simplicity, ability to create intricate components and movable forms, and low running costs. 3D-printed scaffolds can repair bone defects in vivo and in vitro. For 3D printing, variousmaterials including metals, polymers, and ceramics are often employed but polymeric biofilaments are promising candidates for replacing non-biodegradable materials due to their adaptabilityand environment friendliness. This review paper majorly focuses on the fused deposition modeling approach for the fabrication of 3D scaffolds. In addition, it also provides information on biofilaments used in FDM 3D printing, applications, and commercial aspects of scaffolds in bone tissue engineering.

An explainable machine learning-based probabilistic framework for the design of scaffolds in bone tissue engineering.

Recently, 3D-printed biodegradable scaffolds have shown great potential for bone repair in critical-size fractures. The differentiation of the cells on a scaffold is impacted among other factors by the surface deformation of the scaffold due to mechanical loading and the wall shear stresses imposed by the interstitial fluid flow. These factors are in turn significantly affected by the material properties, the geometry of the scaffold, as well as the loading and flow conditions. In this work, a numerical framework is proposed to study the influence of these factors on the expected osteochondral cell differentiation. The considered scaffold is rectangular with a 0/90 lay-down pattern and a four-layered strut made of polylactic acid with a 5% steel particle content. The distribution of the different types of cells on the scaffold surface is estimated through a scalar stimulus, calculated by using a mechanobioregulatory model. To reduce the simulation time for the computation of the stimulus, a probabilistic machine learning (ML)-based reduced-order model (ROM) is proposed. Then, a sensitivity analysis is performed using the Shapley additive explanations to examine the contribution of the various parameters to the framework stimulus predictions. In a final step, a multiobjective optimization procedure is implemented using genetic algorithms and the ROM, aiming to identify the material parameters and loading conditions that maximize the percentage of surface area populated by bone cells while minimizing the area corresponding to the other types of cells and the resorption condition. The results of the performed analysis highlight the potential of using ROMs for the scaffold design, by dramatically reducing the simulation time while enabling the efficient implementation of sensitivity analysis and optimization procedures.

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

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

3D-printed piezoelectric scaffolds composed of uniform core-shell structured BaTiO3@ bioactive glasses particles for bone regeneration

The piezoelectric property and biocompatibility of barium titanate (BTO) is exceptional, whereas its biological activity is limited. Bioactive glasses (BG) are widely recognized for osteoinductive bioactivities. Hence, it is meaningful to explore the reasonable design of BTO and BG combinations to achieve bioactive piezoelectric tissue engineering scaffolds that mimic natural bone. In this study, homogeneous core-shell particles of BTO wrapped in BG layer were firstly fabricated via a sol-gel process. Various BG weight ratios (5 wt%, 10 wt%, and 15 wt%) in BTO@BG particles have been able to achieve the shell thickness in the range of 4 nm–16 nm. Furthermore, the composite particles were three-dimensionally printed into porous scaffolds through gas extrusion using polyvinyl pyrrolidone as binders. The composite scaffolds have been extensively characterized with respect to their physical and functional properties. Desirable piezoelectric scaffolds (BTO@15BG-S) with compressive strength at ∼66 MPa, and piezoelectric constant (d33) of ∼1.1 pC/N were obtained after sintering and polarization. Our findings indicated that higher sintering temperatures led to denser scaffolds with reduced porosity, increased compressive strength and higher d33 constant. Additionally, an increase in the amount of BG coating promoted scaffold calcination via melt filling in pores, while reduced the piezoelectric constant d33. Among all scaffolds, BTO@15BG-S exhibited superior ability to induce apatite formation when sintered at 1250 °C and soaked in simulated body fluid for 7 days. In vitro culture rat bone marrow mesenchymal stem cells (rBMSCs) and cellular assessments confirmed that polarized piezoelectric ceramic scaffolds could effectively enhance cell adhesion, proliferation, and osteogenic differentiation compared to unpolarized scaffolds. An increase in BG coating amount enhanced the capacity of piezoelectric ceramic scaffolds to upgrade osteogenesis activities of rBMSCs. These results rendered BTO@BG-S composite scaffolds promising candidate in the field of bone repair.

Apoptotic extracellular vesicles derived from hypoxia-preconditioned mesenchymal stem cells within a modified gelatine hydrogel promote osteochondral regeneration by enhancing stem cell activity and regulating immunity

Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.Graphical

Cellulose nanocrystals-strengthened, anti-drying, and anti-freezing hydrogels for human motion sensing and 3D printing

Recently, stretchable hydrogels have been widely applied in flexible wearable devices. However, their stability, sensitivity, and mechanical properties still remain significant shortcomings. In this work, a double-network and conductive hydrogel formed by sodium alginate and poly(vinyl alcohol) in a glycerol-water system is developed. The network consists of poly(vinyl alcohol) and sodium alginate with rod-like cellulose nanocrystals as a supporting structure, which provides enhanced mechanical properties such as high tensile strength (2.4 MPa), high toughness (4.61 MJ/m3), high compressive strength (7.83 MPa), as well as excellent fatigue resistance. On one hand, due to the incorporation of salt, the hydrogels are endowed with good electrical conductivity. On the other hand, since the hydrogels exhibit the ability to sense pressure and strain, it is considered to be a sensor that can be used to monitor various movements of human bodies. It is worth mentioning that the addition of glycerol provides the hydrogels good anti-freezing properties, and the hydrogels have an operating temperature tolerance as low as −25 °C, which allows the hydrogels to work well even in winter. In addition, the hydrogel solution has good injectability, gelling rate controllability, and biocompatibility, which makes it a good candidate in 3D printing. In summary, the hydrogel developed in this study has good application scenarios for applications such as electronic skin, flexible wearable devices, strain sensors, and 3D-printed scaffolds.

Vitamin D3 Release from MgO Doped 3D Printed TCP Scaffolds for Bone Regeneration.

Regenerating bone tissue in critical-sized craniofacial bone defects remains challenging and requires the implementation of innovative bone implants with early stage osteogenesis and blood vessel formation. Vitamin D3 is incorporated into MgO-doped 3D-printed scaffolds for defect-specific and patient-specific implants in low load-bearing areas. This novel bone implant also promotes early stage osteogenesis and blood vessel development. Our results show that vitamin D3-loaded MgO-doped 3D-printed scaffolds enhance osteoblast cell proliferation 1.3-fold after being cultured for 7 days. Coculture studies on osteoblasts derived from human mesenchymal stem cells (hMSCs) and osteoclasts derived from monocytes show the upregulation of genes related to osteoblastogenesis and the downregulation of RANK-L, which is essential for osteoclastogenesis. Release of vitamin D3 also inhibits osteoclast differentiation by 1.9-fold after a 21-day culture. After 6 weeks, vitamin D3 release from MgO-doped 3D-printed scaffolds enhances the new bone formation, mineralization, and angiogenic potential. The multifunctional 3D-printed scaffolds can improve early stage osteogenesis and blood vessel formation in craniofacial bone defects.

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 osteogenic drug, i.e., pargyline (PGL) in a controllable manner. Together, our scaffold displayed an on-demand sequential release of those two drugs and could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models. Altogether, this scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.

3D Printing Cervical Implant Scaffolds Incorporated with Drug-Loaded Carboxylated Chitosan Microspheres for Long-Term Anti-HPV Protein Delivery.

As attempting personalized medicine, 3D-printed tissue engineering scaffolds are employed to combine with therapeutic proteins/peptides especially in the clinical treatment of infectious diseases, genetic diseases, and cancers. However, current drug-loading methods, such as immersion and encapsulation, usually lead to the burst release of the drugs. To address these issues, we proposed an integrated strategy toward the long-term controlled release of protein. In this study, patient-customized 3D scaffolds incorporated with drug-loaded microspheres were printed to realize the effective delivery of the anti-human papillomavirus (anti-HPV) protein after cervical conization in the treatment of cervical cancer. The 3D-printed scaffold could provide mechanical support to the defect site and ensure local release of the drug to avoid systemic administration. Meanwhile, microspheres serve as functional components to prevent the inactivation of proteins, as well as regulate their release period to meet the time requirement of different treatment courses. The research also utilized bovine serum albumin as a model protein to validate the feasibility of these scaffolds as a generic technology platform. The bioactivity of the released anti-HPV protein was validated using a pseudovirus model, which demonstrated that the microsphere encapsulation would not cause protein denaturation during the scaffold fabrication process. Besides, 3D-printed scaffolds incorporated with carboxylated chitosan microspheres were biocompatible and beneficial for cell attachment, which have been demonstrated by favorable cell viability and better coverage results for HeLa and HFF-1. This study highlights the great potential of scaffolds incorporated with microspheres to serve as tissue engineering candidate products with the function of effective protein delivery in a long-term controlled manner and personalized shapes for clinical trials.

3D-Printed Magnesium Peroxide-Incorporated Scaffolds with Sustained Oxygen Release and Enhanced Photothermal Performance for Osteosarcoma Multimodal Treatments.

The hypoxic microenvironment in osteosarcoma inevitably compromises the antitumor effect and local bone defect repair, suggesting an urgent need for sustained oxygenation in the tumor. The currently reported oxygen-releasing materials have short oxygen-releasing cycles, harmful products, and limited antitumor effects simply by improving hypoxia. Therefore, the PCL/nHA/MgO2/PDA-integrated oxygen-releasing scaffold with a good photothermal therapy effect was innovatively constructed in this work to achieve tumor cell killing and bone regeneration functions simultaneously. The material distributes MgO2 powder evenly on the scaffold material through 3D printing technology and achieves the effect of continuous oxygen release (more than 3 weeks) through its slow reaction with water. The in vitro and in vivo results also indicate that the scaffold has good biocompatibility and sustained-release oxygen properties, which can effectively induce the proliferation and osteogenic differentiation of bone mesenchymal stem cells, achieving excellent bone defect repair. At the same time, in vitro cell experiments and subcutaneous tumorigenesis experiments also confirmed that local oxygen supply can promote osteosarcoma cell apoptosis, inhibit proliferation, and reduce the expression of heat shock protein 60, thereby enhancing the photothermal therapy effect of polydopamine and efficiently eliminating osteosarcoma. Taken together, this integrated functional scaffold provides a unique and efficient approach for antitumor and tumor-based bone defect repair for osteosarcoma treatment.

Advanced Bioresin Formulation for 3D-Printed Bone Scaffolds: PCLDMA and p-PLA Integration.

In bone tissue engineering, scaffold attributes such as pore dimensions and mechanical strength are crucial. This study synthesized polycaprolactone dimethacrylate (PCLDMA) from polycaprolactone (PCL), incorporating epichlorohydrin (Epi-PCL) and methacryloyl chloride (Meth-Cl). PCLDMA was blended with polylactic acid (p-PLA) to 3D-print bone scaffolds using stereolithography (SLA). Analytical techniques included nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and compression testing. Degradation kinetics and cell viability were investigated using human osteoblast (HOB) cells. Findings revealed PCLDMA/p-PLA composite scaffold superiority over the original polymers. Notably, PCLDMA-60 (60% PCLDMA, 40% p-PLA) displayed optimal properties. Compressive strength varied from 0.019 to 16.185 MPa, porosity from 2% to 50%, and degradation rates from 0% to 0.4% over three days. Cell viability assays affirmed biocompatibility across various PCLDMA ratios. In conclusion, PCLDMA/p-PLA composite scaffolds, particularly PCLDMA-60, show great potential in bone tissue engineering.

Multidimensional 3D-Printed Scaffolds and Regeneration of Intrabony Periodontal Defects: A Systematic Review.

The utilization of regenerative techniques in periodontology involves tailoring tissue engineering principles to suit the oral cavity's unique environment. Advancements in computer-assisted technology, specifically utilizing cone beam computed tomography (CBCT), enabled the fabrication of 3D-printed scaffolds. The current review aims to explore whether 3D-printed scaffolds are effective in promoting osteogenesis in patients with periodontal defects. A thorough exploration was undertaken across seven electronic databases (PubMed, Scopus, ScienceDirect, Google Scholar, Cochrane, Web of Science, Ovid) to detect pertinent research in accordance with specified eligibility criteria, aligning with the PRISMA guidelines. Two independent reviewers undertook the screening and selection of manuscripts, executed data extraction, and evaluated the bias risk using the Newcastle-Ottawa Scale for non-randomized clinical trials and SYRCLE's risk of bias tool for animal studies. Initially, 799 articles were identified, refined by removing duplicates. After evaluating 471 articles based on title and abstract, 18 studies remained for full-text assessment. Eventually, merely two manuscripts fulfilled all the eligibility criteria concerning human trials. Both studies were prospective non-randomized clinical trials. Moreover, 11 animal studies were also included. The use of multidimensional, 3D-printed, customized scaffolds appears to stimulate periodontal regeneration. While the reported results are encouraging, additional studies are required to identify the ideal characteristics of the 3D scaffold to be used in the regeneration of periodontal tissue.

The Role of Cone Beam Computed Tomography in Periodontology: From 3D Models of Periodontal Defects to 3D-Printed Scaffolds.

The treatment of osseous defects around teeth is a fundamental concern within the field of periodontology. Over the years, the method of grafting has been employed to treat bone defects, underscoring the necessity for custom-designed scaffolds that precisely match the anatomical intricacies of the bone cavity to be filled, preventing the formation of gaps that could allow the regeneration of soft tissues. In order to create such a patient-specific scaffold (bone graft), it is imperative to have a highly detailed 3D representation of the bone defect, so that the resulting scaffold aligns with the ideal anatomical characteristics of the bone defect. In this context, this article implements a workflow for designing 3D models out of patient-specific tissue defects, fabricated as scaffolds with 3D-printing technology and bioabsorbable materials, for the personalized treatment of periodontitis. The workflow is based on 3D modeling of the hard tissues around the periodontal defect (alveolar bone and teeth), scanned from patients with periodontitis. Specifically, cone beam computed tomography (CBCT) data were acquired from patients and were used for the reconstruction of the 3D model of the periodontal defect. The final step encompasses the 3D printing of these scaffolds, employing Fused Deposition Modeling (FDM) technology and 3D-bioprinting, with the aim of verifying the design accuracy of the developed methodοlogy. Unlike most existing 3D-printed scaffolds reported in the literature, which are either pre-designed or have a standard structure, this method leads to the creation of highly detailed patient-specific grafts. Greater accuracy and resolution in the macroarchitecture of the scaffolds were achieved during FDM printing compared to bioprinting, with the standard FDM printing profile identified as more suitable in terms of both time and precision. It is easy to follow and has been successfully employed to create 3D models of periodontal defects and 3D-printed scaffolds for three cases of patients, proving its applicability and efficiency in designing and fabricating personalized 3D-printed bone grafts using CBCT data.

Avastin-Loaded 3D-Printed Alginate Scaffold as an Effective Antiadhesive Barrier to Prevent Postsurgical Adhesion Bands Formation.

Postoperative adhesion can cause complications, such as pain and organ blockage, in the abdominal regions. To address this issue, surgical techniques and antiadhesive treatments are applied. Given the significant role of vascularization in adhesion band formation, Avastin (Ava) that targets vascular endothelial growth factor (VEGF) can be applied to prevent peritoneal adhesion bands. Moreover, Alginate (Alg), a natural polysaccharide, is a promising physical barrier to prevent adhesion bands. Incorporating Ava into Alg hydrogel in a form of 3D-printed scaffold (Alg/Ava) has potential to suppress inflammation and angiogenesis, leading to reduce peritoneal adhesion bands. Following physical, morphological, and biocompatibility evaluations, the efficacy of Alg and Ava alone and their combination in Alg/Ava on the formation of postsurgical adhesions is evaluated. Upon confirming physical stability and sustained release of Ava, the Alg/Ava scaffold effectively diminishes both the extent and strength of adhesion bands. Histopathological examination shows that the reduction in fibrosis and inflammation is responsible for preventing adhesion bands by the Alg/Ava scaffold. Additionally, the cytokine assessment reveals that this is due to the inhibition in the secretion of VEGF and Interleukin 6 suppressing vascularization and inflammatory pathways. This study suggests that a 3D-printed Alg/Ava scaffold has great potential to prevent the postsurgical adhesion bands.

Mn Single-Atom Nanozyme Functionalized 3D-Printed Bioceramic Scaffolds for Enhanced Antibacterial Activity and Bone Regeneration.

Infective bone defect is increasingly threatening human health. How to achieve the optimal antibacterial activity and regenerative repair of infective bone defect simultaneously is a huge challenge in clinic. Herein, this work reports a rational integration of Mn single-atom nanozyme into the 3D-printed bioceramic scaffolds (Mn/HSAE@BCP scaffolds). The integrated Mn/HSAE@BCP scaffolds can catalyze the conversion of H2O2 to produce hydroxyl radical (•OH) and superoxide anion (O2 •-) through cascade reaction. Besides, the prominent thermal conversion efficiency of Mn/HSAE@BCP scaffolds can be utilized for sonodynamic therapy (SDT). The synergetic strategy of chemodynamic therapy (CDT)/SDT enables the sufficient generation of reactive oxygen species (ROS) to kill Staphylococcus aureus (S. aureus) or Escherichia coli (E. coli). Furthermore, the enhanced antibacterial efficacy of Mn/HSAE@BCP scaffolds is beneficial to upregulate the expression of osteogenesis-related markers (such as collagen 1(COL1), Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteoprotegerin (OPG)) in vitro and further promote bone regeneration in vivo. The results demonstrate the good potential of Mn/HSAE@BCP scaffolds for the enhanced antibacterial activity and bone regeneration, which provide an effective method for the treatment of clinical infective bone defect.

A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration

BackgroundCoordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities.ResultsHerein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-β (TGF-β) signaling pathway.ConclusionOverall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.Graphical