Bionic Scaffold Research Articles

Mechanical memory based biofabrication of hierarchical elastic cardiac tissue

Mimicking the multilayered, anisotropic, elastic structure of cardiac tissues for controlled guidiance of 3D cellular orientation is essential in designing bionic scaffolds for cardiac tissue biofabrication. Here, a hierarchically organized, anisotropic, wavy and conductive polycaprolactone/Au scaffold was created in a facile fashion based on mechanical memory during fabrication. The bionic 3D scaffold shows good biocompatibility, excellent biomimetic mechanical properties that guide myoblast alignment, support the hyperelastic behavior observed in native cardiac muscle tissue, and promote myotube maturation, which holds potential for cardiac muscle engineering and the establishment of anin vitroculture platform for drug screening.

Natural loofah sponge inspired 3D printed bionic scaffolds promote personalized bone defect regeneration

Critical-sized bone defects pose serious health concerns for patients. Clinically, the use of functionalized bone implants has emerged as an effective solution. However, the rapid advancement in drug and biomaterials has led to an increasing design cost, triggering discussions in the field about how to efficiently create customized functional bone implants. Inspired by the unique structure of natural loofah sponges that effectively deliver nutrients to seeds, we designed a functionalized bone implant emulating this structure. Drug-release gradients were achieved through the application of different concentrations of hydrogels within the composite scaffold. This approach allowed active substances to be released outwardly during the early stage of bone repair, sustaining a local drug micro-environment within the implant scaffold that promotes angiogenesis and osteogenic differentiation in damaged areas. In vivo experiments showed that our loofah sponge bionic scaffold outperformed traditional hydroxyapatite scaffolds by promoting both bone and vascular regeneration. We expect the design of loofah sponge bionic scaffold could potentially deliver an effective strategy in the development of functionalized bone implants.

Application and progress of bionic scaffolds in nerve repair: a narrative review

Nerve injury can result in severe damage and potentially permanent disability, imposing substantial physical, psychological, and economic burdens on affected individuals and their families. Despite advances in surgical repair techniques, the functional recovery of nerves remains suboptimal. The current therapeutic approaches for nerve injury exhibit limited efficacy in restoring function, underscoring the imperative for the development of innovative treatment modalities. In recent years, bionics has emerged as a promising field in medicine, particularly in the treatment and rehabilitation of nerve injuries. We review the advances in the application of bionic technology within the realm of nerve injury treatment, encompassing bionic nerve scaffolds, nerve regeneration materials, and nerve modulation techniques. We delve into how these technologies may facilitate the repair and functional restoration of nerve tissues, as well as the challenges they encounter in clinical translation and their prospective directions for future development. Furthermore, we explore the convergence of bionic technology with existing therapeutic strategies and discuss the potential for interdisciplinary collaboration to catalyze innovation in nerve injury treatment. The integration of bionics with conventional methods may offer a synergistic approach, enhancing the efficacy of nerve repair and rehabilitation processes.

Supramolecular Composite Hydrogel Loaded with CaF2 Nanoparticles Promotes the Recovery of Periodontitis Bone Resorption.

Treatments to reduce periodontal inflammation and rescue periodontitis bone resorption have been of interest to researchers. Bone tissue engineering materials have been gradually used in the treatment of bone defects, but periodontal bone tissue regeneration still faces challenges. Considering the biocompatibility factor, constructing bionic scaffolds with natural extracellular matrix properties is an ideal therapeutic pathway. Based on the pathological mechanism of periodontitis, in this study, short peptide and nanometer inorganic particles were comingled to construct NapKFF-nano CaF2 supramolecular composite hydrogels with different ratios. Material characterization experiments confirmed that the composite hydrogel had suitable mechanical properties and a three-dimensional structure that can function in the resorption region of the alveolar bone and provide spaces for cell proliferation and adhesion. The release of low concentrations of fluoride and calcium ions has been shown to have positive biological effects in both in vivo and in vitro experiments. Vitro experiments confirmed that the composite hydrogel had good biocompatibility and promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Microbiological experiments confirmed that the composite hydrogel inhibited the activity of periodontal pathogenic bacteria. In animal studies, composite hydrogel applied to periodontitis rats in vivo can effectively repair alveolar bone resorption. This composite hydrogel has a simple preparation method and is inexpensive to produce, yet it has antibacterial and osteogenesis-promoting incremental effects, which makes it well suited for the treatment of periodontitis bone resorption, providing a new strategy for periodontal bone tissue engineering.

Glucosamine sulfate-loaded nanofiber reinforced carboxymethyl chitosan sponge for articular cartilage restoration

Cartilage is severely limited in self-repair after damage, and tissue engineering scaffold transplantation is considered the most promising strategy for cartilage regeneration. However, scaffolds without cells and growth factors, which can effectively avoid long cell culture times, high risk of infection, and susceptibility to contamination, remain scarce. Hence, we developed a cell- and growth factor-dual free hierarchically structured nanofibrous sponge to mimic the extracellular matrix, in which the encapsulated core–shell nanofibers served both as mechanical supports and as long-lasting carriers for bioactive biomass molecules (glucosamine sulfate). Under the protection of the nanofibers in this designed sponge, glucosamine sulfate could be released continuously for at least 30 days, which significantly accelerated the repair of cartilage tissue in a rat cartilage defect model. Moreover, the nanofibrous sponge based on carboxymethyl chitosan as the framework could effectively fill irregular cartilage defects, adapt to the dynamic changes during cartilage movement, and maintain almost 100 % elasticity even after multiple compression cycles. This strategy, which combines fiber freeze-shaping technology with a controlled-release method for encapsulating bioactivity, allows for the assembly of porous bionic scaffolds with hierarchical nanofiber structure, providing a novel and safe approach to tissue repair.

Enhancing Osteogenic Differentiation of Dental Pulp Stem Cells with Covalently Bonded All‐Carbon Scaffolds

AbstractThe regeneration of bone tissue is a complex process requiring innovative biomaterials with enhanced osteogenic properties to facilitate successful tissue engineering. Herein, a 3D bionic scaffold comprised of covalently bound graphene/carbon nanotube monoliths are present (3DGp/CNTs) exhibiting long‐range ordered porous characteristics, showcasing promising attributes for bone tissue applications. The lightweight, all‐carbon scaffolds not only demonstrate excellent mechanical performance in the hydrated state but also mimic the structural and functional features of the extracellular matrix, actively promoting cellular adhesion, proliferation, and differentiation. Significantly, the osteogenic differentiation of dental pulp stem cells (DPSCs) is observed, as evidenced by the upregulation of RUNX2, OSX, BSP, ALP, OPN, and OCN expression. This notable outcome can be attributed to the synergistic effect of 3DGp/CNTs, which create a conducive microenvironment for DPSCs and promote osteogenic differentiation by activating the BMP pathway. This observation elucidates the mechanism through which 3DGp/CNTs induce DPSC mineralization. The combination of these advantages, along with its straightforward and cost‐effective preparation technique, positions 3DGp/CNTs as a promising candidate for dental clinical engineering.

Creating a bionic scaffold via light-curing liquid crystal ink to reveal the role of osteoid-like microenvironment in osteogenesis

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.

Fabrication of a Triple-Layer Bionic Vascular Scaffold via Hybrid Electrospinning.

Tissue engineering aims to develop bionic scaffolds as alternatives to autologous vascular grafts due to their limited availability. This study introduces a novel wet-electrospinning fabrication technique to create small-diameter, uniformly aligned tubular scaffolds. By combining this innovative method with conventional electrospinning, a bionic tri-layer scaffold that mimics the zonal structure of vascular tissues is produced. The inner and outer layers consist of PCL/Gelatin and PCL/PLGA fibers, respectively, while the middle layer is crafted using PCL through Wet Vertical Magnetic Rod Electrospinning (WVMRE). The scaffold's morphology is analyzed using Scanning Electron Microscopy (SEM) to confirm its bionic structure. The mechanical properties, degradation profile, wettability, and biocompatibility of the scaffold are also characterized. To enhance hemocompatibility, the scaffold is crosslinked with heparin. The results demonstrate sufficient mechanical properties, good wettability of the inner layer, proper degradability of the inner and middle layers, and overall good biocompatibility. In conclusion, this study successfully develops a small-diameter tri-layer tubular scaffold that meets the required specifications.

Design and optimization of Anisotropy–Inspired AlSi10Mg metamaterials with tailored mechanics and mass transport properties in tissue engineering

Metamaterials are widely used for achieving tailored multi–physical properties. However, it is challenging to satisfy multiple property requirements simultaneously. For example, the mechanical and mass transport properties of bionic scaffolds have to be compromised. In this work, 3D–printed metamaterials with adjustable topological features are proposed, and a topological optimization strategy for coordinating multiple properties is developed. Tradeoffs between the mechanics, energy absorption capacity, and mass transport properties are accomplished under given a porosity. Anisotropic metamaterials with permeabilities of 2.34 ∼ 3.44 × 10-7 m2 and elastic moduli of 1.37 ∼ 3.14 GPa were obtained, and the gradient scaffolds were further designed to realize adjustable local characteristics. The optimized design technique described here can serve as an effective way to design more complex multilayered scaffolds with structural characteristics and biomechanical properties similar to those of natural tissue, so as to achieve an unprecedented level of tailoring multi–physics properties in tissue engineering, especially in the design of gradient scaffolds. Our study also represents advances in property decoupling, individual customization and collaborative design of metamaterials, which can be generalized to fluid and heat transport fields.

Trilayered biomimetic hydrogel scaffolds with dual-differential microenvironment for articular osteochondral defect repair

Commonly, articular osteochondral tissue exists significant differences in physiological architecture, mechanical function, and biological microenvironment. However, the development of biomimetic scaffolds incorporating upper cartilage, middle tidemark-like, and lower subchondral bone layers for precise articular osteochondral repair remains elusive. This study proposed here a novel strategy to construct the trilayered biomimetic hydrogel scaffolds with dual-differential microenvironment of both mechanical and biological factors. The cartilage-specific microenvironment was achieved through the grafting of kartogenin (KGN) into gelatin via p-hydroxyphenylpropionic acid (HPA)-based enzyme crosslinking reaction as the upper cartilage layer. The bone-specific microenvironment was achieved through the grafting of atorvastatin (AT) into gelatin via dual-crosslinked network of both HP-based enzyme crosslinking and glycidyl methacrylate (GMA)-based photo-crosslinking reactions as the lower subchondral bone layer. The introduction of tidemark-like middle layer is conducive to the formation of well-defined cartilage-bone integrated architecture. The in vitro experiments demonstrated the significant mechanical difference of three layers, successful grafting of drugs, good cytocompatibility and tissue-specific induced function. The results of in vivo experiments also confirmed the mechanical difference of the trilayered bionic scaffold and the ability of inducing osteogenesis and chondrogenesis. Furthermore, the articular osteochondral defects were successfully repaired using the trilayered biomimetic hydrogel scaffolds by the activation of endogenous recovery, which offers a promising alternative for future clinical treatment.

Synergistic large segmental bone repair by 3D printed bionic scaffolds and engineered ADSC nanovesicles: Towards an optimized regenerative microenvironment

Achieving sufficient bone regeneration in large segmental defects is challenging, with the structure of bone repair scaffolds and their loaded bioactive substances crucial for modulating the local osteogenic microenvironment. This study utilized digital laser processing (DLP)-based 3D printing technology to successfully fabricate high-precision methacryloylated polycaprolactone (PCLMA) bionic bone scaffold structures. Adipose-derived stem cell-engineered nanovesicles (ADSC-ENs) were uniformly and stably modified onto the bionic scaffold surface using a perfusion device, constructing a conducive microenvironment for tissue regeneration and long bone defect repair through the scaffold's structural design and the vesicles' biological functions. Scanning electron microscopy (SEM) examination of the scaffold surface confirmed the efficient loading of ADSC-ENs. The material group loaded with vesicles (PCLMA-BAS-ENs) demonstrated good cell compatibility and osteogenic potential when analyzed for the adhesion and osteogenesis of primary rabbit bone marrow mesenchymal stem cells (BMSCs) on the material surface. Tested in a 15 mm critical rabbit radial defect model, the PCLMA-BAS-ENs scaffold facilitated near-complete bone defect repair after 12 weeks. Immunofluorescence and proteomic results indicated that the PCLMA-BAS-ENs scaffold significantly improved the osteogenic microenvironment at the defect site in vivo, promoted angiogenesis, and enhanced the polarization of macrophages towards M2 phenotype, and facilitated the recruitment of BMSCs. Thus, the PCLMA-BAS-ENs scaffold was proven to significantly promote the repair of large segmental bone defects. Overall, this strategy of combining engineered vesicles with highly biomimetic scaffolds to promote large-segment bone tissue regeneration holds great potential in orthopedic and other regenerative medicine applications.

Lysophosphatidic Acid/Polydopamine-Modified nHA Composite Scaffolds for Enhanced Osteogenesis via Upregulating the Wnt/Beta-Catenin Pathway.

Guided bone regeneration (GBR) technology has been widely used for the regeneration of periodontal bone defects. However, the limited mechanical properties and bone regeneration potential of the currently available GBR membranes often limit their repair effectiveness. In this paper, serum-derived growth factor lysophosphatidic acid (LPA) nanoparticles and dopamine-decorative nanohydroxyapatite (pDA/nHA) particles were double-loaded into polylactic-glycolic acid/polycaprolactone (PLGA/PCL) scaffolds as an organic/inorganic biphase delivery system, namely, PP-pDA/nHA-LPA scaffolds. Physicochemical properties and osteogenic ability in vitro and in vivo were performed. Scanning electron microscopy and mechanical tests showed that the PP-pDA/nHA-LPA scaffolds had a 3D bionic scaffold structure with improved mechanical properties. In vitro cell experiments demonstrated that the PP-pDA/nHA-LPA scaffolds could significantly enhance the attachment, proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. In vivo, the PP-pDA/nHA-LPA scaffolds exhibited great cytocompatibility and cell recruitment ability in 2- and 4-week subcutaneous implantation experiments and significantly promoted bone regeneration in the periodontal defect scaffold implantation experiment. Moreover, LPA-loaded scaffolds were confirmed to enhance osteogenic activities by upregulating the expression of β-catenin and further activating the Wnt/β-catenin pathway. These results demonstrate that the biphase PP-pDA/nHA-LPA delivery system is a promising material for the GBR.

Bioactive Conjugated Polymer‐Based Biodegradable 3D Bionic Scaffolds for Facilitating Bone Defect Repair (Adv. Healthcare Mater. 7/2024)

Bioactive Conjugated Polymer‐Based Biodegradable 3D Bionic Scaffolds for Facilitating Bone Defect Repair (Adv. Healthcare Mater. 7/2024)

Hierarchical Scaffold with Directional Microchannels Promotes Cell Ingrowth for Bone Regeneration.

Bone regenerative scaffolds with a bionic natural bone hierarchical porous structure provide a suitable microenvironment for cell migration and proliferation. Here, a bionic scaffold (DP-PLGA/HAp) with directional microchannels is prepared by combining 3D printing and directional freezing technology. The 3D printed framework provides structural support for new bone tissue growth, while the directional pore embedded in the scaffolds provides an express lane for cell migration and nutrition transport, facilitating cell growth and differentiation. The hierarchical porous scaffolds achieve rapid infiltration and adhesion of bone marrow mesenchymal stem cells (BMSCs) and improve the expression of osteogenesis-related genes. The rabbit cranial defect experiment presents significant new bone formation, demonstrating that DP-PLGA/HAp offers an effective means to guide cranial bone regeneration. The combination of 3D printing and directional freezing technology might be a promising strategy for developing bone regenerative biomaterials.

Plant-derived exosomes extracted from Lycium barbarum L. loaded with isoliquiritigenin to promote spinal cord injury repair based on 3D printed bionic scaffold.

Plant-derived exosomes (PEs) possess an array of therapeutic properties, including antitumor, antiviral, and anti-inflammatory capabilities. They are also implicated in defensive responses to pathogenic attacks. Spinal cord injuries (SCIs) regeneration represents a global medical challenge, with appropriate research concentration on three pivotal domains: neural regeneration promotion, inflammation inhibition, and innovation and application of regenerative scaffolds. Unfortunately, the utilization of PE in SCI therapy remains unexplored. Herein, we isolated PE from the traditional Chinese medicinal herb, Lycium barbarum L. and discovered their inflammatory inhibition and neuronal differentiation promotion capabilities. Compared with exosomes derived from ectomesenchymal stem cells (EMSCs), PE demonstrated a substantial enhancement in neural differentiation. We encapsulated isoliquiritigenin (ISL)-loaded plant-derived exosomes (ISL@PE) from L. barbarum L. within a 3D-printed bionic scaffold. The intricate construct modulated the inflammatory response following SCI, facilitating the restoration of damaged axons and culminating in ameliorated neurological function. This pioneering investigation proposes a novel potential route for insoluble drug delivery via plant exosomes, as well as SCI repair. The institutional animal care and use committee number is UJS-IACUC-2020121602.

Progress in methods for evaluating Schwann cell myelination and axonal growth in peripheral nerve regeneration via scaffolds.

Peripheral nerve injury (PNI) is a neurological disorder caused by trauma that is frequently induced by accidents, war, and surgical complications, which is of global significance. The severity of the injury determines the potential for lifelong disability in patients. Artificial nerve scaffolds have been investigated as a powerful tool for promoting optimal regeneration of nerve defects. Over the past few decades, bionic scaffolds have been successfully developed to provide guidance and biological cues to facilitate Schwann cell myelination and orientated axonal growth. Numerous assessment techniques have been employed to investigate the therapeutic efficacy of nerve scaffolds in promoting the growth of Schwann cells and axons upon the bioactivities of distinct scaffolds, which have encouraged a greater understanding of the biological mechanisms involved in peripheral nerve development and regeneration. However, it is still difficult to compare the results from different labs due to the diversity of protocols and the availability of innovative technologies when evaluating the effectiveness of novel artificial scaffolds. Meanwhile, due to the complicated process of peripheral nerve regeneration, several evaluation methods are usually combined in studies on peripheral nerve repair. Herein, we have provided an overview of the evaluation methods used to study the outcomes of scaffold-based therapies for PNI in experimental animal models and especially focus on Schwann cell functions and axonal growth within the regenerated nerve.

Bioactive Conjugated Polymer-Based Biodegradable 3D Bionic Scaffolds for Facilitating Bone Defect Repair.

Bone defect regeneration is one of the great clinical challenges. Suitable bioactive composite scaffolds with high biocompatibility, robust new-bone formation capability and degradability are still required. This work designs and synthesizes an unprecedented bioactive conjugated polymer PT-C3 -NH2 , demonstrating low cytotoxicity, cell proliferation/migration-promoting effect, as well as inducing cell differentiation, namely regulating angiogenesis and osteogenesis to MC3T3-E1 cells. PT-C3 -NH2 is incorporated into polylactic acid-glycolic acid (PLGA) scaffolds, which is decorated with caffeic acid (CA)-modified gelatin (Gel), aiming to improve the surface water-wettability of PLGA and also facilitate to the linkage of conjugated polymer through catechol chemistry.A3D composite scaffoldPLGA@GC-PT is then generated. This scaffolddemonstrates excellent bionic structures with pore size of 50-300µm and feasible biodegradation ability. Moreover, it also exhibites robust osteogenic effect to promote osteoblast proliferation and differentiation in vitro, thus enabling the rapid regeneration of bone defects in vivo. Overall, this study provides a new bioactive factor and feasible fabrication approach of biomimetic scaffold for bone regeneration.

Bionic peptide scaffold in situ polarization and recruitment of M2 macrophages to promote peripheral nerve regeneration.

Tissue regeneration requires exogenous and endogenous signals, and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells. The short-distance peripheral nerve showed a spontaneous regenerative phenomenon, which was initiated by the guiding role of macrophages. However, it cannot sufficiently restore long-distance nerve injury by itself. Based on this principle, we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves. Furthermore, a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles (EVs). The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner. The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells, neuron growth and motor function recovery. Meanwhile, the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction. Overall, we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve. This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment, favoring long-distance peripheral nerve regeneration. It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration, which facilitating the development of pro-regenerative biomaterials.

Emerging biotechnologies and biomedical engineering technologies for hearing reconstruction.

Hearing impairment is a global health problem that affects social communications and the economy. The damage and loss of cochlear hair cells and spiral ganglion neurons (SGNs) as well as the degeneration of neurites of SGNs are the core causes of sensorineural hearing loss. Biotechnologies and biomedical engineering technologies provide new hope for the treatment of auditory diseases, which utilizes biological strategies or tissue engineering methods to achieve drug delivery and the regeneration of cells, tissues, and even organs. Here, the advancements in the applications of biotechnologies (including gene therapy and cochlear organoids) and biomedical engineering technologies (including drug delivery, electrode coating, electrical stimulation and bionic scaffolds) in the field of hearing reconstruction are presented. Moreover, we summarize the challenges and provide a perspective on this field.

3D-printed PCL scaffolds with anatomy-inspired bionic stratified structures for the treatment of growth plate injuries

The growth plate is a cartilaginous tissue with three distinct zones. Resident chondrocytes are highly organized in a columnar structure, which is critical for the longitudinal growth of immature long bones. Once injured, the growth plate may potentially be replaced by bony bar formation and, consequently, cause limb abnormalities in children. It is well-known that the essential step in growth plate repair is the remolding of the organized structure of chondrocytes. To achieve this, we prepared an anatomy-inspired bionic Poly(ε-caprolactone) (PCL) scaffold with a stratified structure using three-dimensional (3D) printing technology. The bionic scaffold is engineered by surface modification of NaOH and collagen Ⅰ (COL Ⅰ) to promote cell adhesion. Moreover, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are loaded in the most suitable ratio of 1:3 for growth plate reconstruction. Based on the anatomical structure of the growth plate, the bionic scaffold is designed to have three regions, which are the small-, medium-, and large-pore-size regions. These pore sizes are used to induce BMSCs to differentiate into similar structures such as the growth plate. Remarkably, the X-ray and histological results also demonstrate that the cell-loaded stratified scaffold can successfully rebuild the structure of the growth plate and reduce limb abnormalities, including limb length discrepancies and angular deformities in vivo. This study provides a potential method of preparing a bioinspired stratified scaffold for the treatment of growth plate injuries.