Scaffolds For Repair Research Articles

Improvement of Osteogenic Differentiation of Mouse Pre-Osteoblastic MC3T3-E1 Cells on Core-Shell Polylactic Acid/Chitosan Electrospun Scaffolds for Bone Defect Repair.

Electrospun hybrid scaffolds composed of synthetic and natural polymers have gained increasing interest in tissue engineering applications over the last decade. In this work, scaffolds composed of polylactic acid electrospun fibers, either treated (P-PLA) or non-treated (PLA) with air-plasma, were coated with high molecular weight chitosan to create a core-shell microfibrous structure. The effective thickness control of the chitosan layer was confirmed by gravimetric, spectroscopic (FTIR-ATR) and morphological (SEM) investigations. The chitosan coating increased the fiber diameter of the microfibrous scaffolds while the tensile mechanical tests, conducted in dry and wet environments, showed a reinforcing action of the coating layer on the scaffolds, in particular when deposited on P-PLA samples. The stability of the Chi coating on both PLA and P-PLA substrates was confirmed by gravimetric analysis, while their mineralization capacity was evaluated though scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) after immersing the scaffolds in simulated body fluids (SBF) at 37 °C for 1 week. Sample biocompatibility was investigated through cell viability assay and SEM analysis on mouse pre-osteoblastic MC3T3-E1 cells grown on scaffolds at different times (1, 7, 14 and 21 days). Finally, Alizarin Red assay and qPCR analysis suggested that the combination of plasma treatment and chitosan coating on PLA electrospun scaffolds influences the osteoblastic differentiation of MC3T3-E1 cells, thus demonstrating the great potential of P-PLA/chitosan hybrid scaffolds for bone tissue engineering applications.

Stem Cells and Bone Tissue Engineering.

Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in the incorporation with the host bone as well as its cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells that are delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells, including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells, urine-derived stem cells, stem cells from apical papilla, and induced pluripotent stem cells, for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles that are delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hoped that in the future, these preclinical results will translate into new regenerative therapies for bone defect repair.

3D printed polycaprolactone/β-tricalcium phosphate/carbon nanotube composite – Physical properties and biocompatibility

Three-dimensional (3D) printing is a bio-fabrication technique used to process tissue-engineered scaffolds for bone repair and remodeling. Polycaprolactone (PCL)/β-tricalcium phosphate (TCP) has been used as a base and osteoconductive biomaterial for bone tissue engineering in the past decades. The current study reveals the fabrication of a polycaprolactone (PCL)/β-tricalcium phosphate (TCP) scaffold by incorporating carbon nanotubes (CNT) via 3D printing. The physical properties and cytocompatibility of a new type of tissue engineering composite from polycaprolactone/β-tri-calcium phosphate/carbon nanotubes were investigated, and it was an absorbable scaffold prepared via furnace deposition 3D printing technology. The scaffold was designed with CAD software, and the composite material was fabricated via 3D printing. The printed composite material was tested for mechanical strength, scanning electron microscope (SEM) analysis, porosity calculation, systemic toxicity test, hemolysis rate determination, and effect on the proliferation of rat adipose-derived stem cells cultured in vitro. A composite scaffold with a length of 15 mm, width of 10 mm, and height of 5 mm was manufactured through CAD software drawing and 3D printing technology. Scanning electron microscopy measurements and analysis of the internal pore size of the stent are appropriate; the pores are interconnected, and the mechanical strength matches the strength of human cancellous bone. The calculated porosity of the stent was >60%, non-toxic, and non-hemolytic. The proliferation activity of the ADSC co-cultured with different scaffold materials was as follows: polycaprolactone/β-tricalcium phosphate/0.2% carbon nanotube scaffolds > polycaprolactone/β-tricalcium phosphate/0.1% carbon nanotube scaffolds > polycaprolactone/β-tricalcium phosphate/0.3% carbon nanotube scaffolds > polycaprolactone/β-tricalcium phosphate scaffolds (P < 0.05). The results showed that polycaprolactone/β-tricalcium phosphate/0.2% carbon nanotube scaffolds promoted the adhesion and proliferation of ADSC. The combination of 3D printing technology and CAD software can be used to print personalized composite stents, which have the characteristics of repeatability, high precision, and low cost. Through 3D printing technology, combining a variety of materials with each other can provide the greatest advantages of materials. The waste of resources was avoided. The prepared polycaprolactone/β-tri-calcium phosphate/0.2% carbon nanotube scaffold has a good pore structure and mechanical properties that mimic human cancellous bone, is non-toxic and non-hemolytic, and is effective in promoting ADSC proliferation in vitro. Given this correspondence, 3D printed scaffold shows good biocompatibility and strength, and the fabrication method provides a proof of concept for developing scaffolds for bone tissue engineering applications.

Usefulness of platelet-rich fibrin as a scaffold for meniscal repair: A non-randomized controlled cohort/follow-up study

BackgroundAlthough regenerative medicine treatment is still in its infancy in Japan, legislation within the past decade has provided opportunities to explore new treatment methods using regenerative medicine. We conducted a 2-year prospective follow-up study to statistically analyze treatment outcomes using platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) as effective scaffolds in meniscal repair.Questions/Purposes.1. Does the use of PRF and PRP for meniscal repair surgery regenerate the meniscus?2. Does augmentation of meniscal repair with PRF effectively improve knee function outcomes? MethodsThirty-five patients underwent arthroscopic meniscal repair with PRP and PRF using new devices with all-inside techniques. Among these, 31 patients were evaluated for clinical outcomes postoperatively, and magnetic resonance imaging (MRI) findings were evaluated. The variables were coded appropriately by creating a new column based on the Kellgren–Lawrence classification over time. Log transformation of different time points (pre, post 6, 12, or 24 months) in relation to Lysholm, International Knee Documentation Committee (IKDC), Japanese Orthopedic Association (JOA), and Tegner scores were performed. Follow-up arthroscopy using a needle scope was performed in some cases 2 years later. The PRP and PRF used were characterized using the Minimum Information for Studies Evaluating Biologics in Orthopaedics classification. ResultsOverall, 31 patients were evaluated (mean age = 39.1 ± 15.7 years; preoperative rehabilitation period = 9.5 ± 7.7 weeks). The PRP had mean platelet and white blood cell concentrations of approximately 5.5- and 3.6-fold, respectively. A significant association existed between sex and deformity deterioration but not in age between the two groups classified by deformity deterioration. Surgical intervention significantly and positively impacted knee function, although no significant changes were found in the activity of the participants over time. MRI findings showed no regeneration of the repaired meniscus; nevertheless, none of them worsened. Furthermore, a case where the traumatic cartilage defect was covered with fibrocartilage-like tissue as a secondary finding was observed. ConclusionsMeniscal repair surgery using PRP/PRF is an effective treatment option for improving knee function in patients with knee deformity. Level of evidenceLevel III, Non-randomized controlled cohort/follow-up study.

Three-Dimensional Bioprinting of Strontium-Modified Controlled Assembly of Collagen Polylactic Acid Composite Scaffold for Bone Repair.

In recent years, the incidence of bone defects has been increasing year by year. Bone transplantation has become the most needed surgery after a blood transfusion and shows a rising trend. Three-dimensional-printed implants can be arbitrarily shaped according to the defects of tissues and organs to achieve perfect morphological repair, opening a new way for non-traumatic repair and functional reconstruction. In this paper, strontium-doped mineralized collagen was first prepared by an in vitro biomimetic mineralization method and then polylactic acid was homogeneously blended with the mineralized collagen to produce a comprehensive bone repair scaffold by a gas extrusion 3D printing method. Characterization through scanning electron microscopy, X-ray diffraction, and mechanical testing revealed that the strontium-functionalized composite scaffold exhibits an inorganic composition and nanostructure akin to those of human bone tissue. The scaffold possesses uniformly distributed and interconnected pores, with a compressive strength reaching 21.04 MPa. The strontium doping in the mineralized collagen improved the biocompatibility of the scaffold and inhibited the differentiation of osteoclasts to promote bone regeneration. This innovative composite scaffold holds significant promise in the field of bone tissue engineering, providing a forward-thinking solution for prospective bone injury repair.

Fabrication of Rosuvastatin-Incorporated Polycaprolactone -Gelatin Scaffold for Bone Repair: A Preliminary In Vitro Study.

Rosuvastatin (RSV) is a hydrophilic, effective statin with a long half-life that stimulates bone regeneration. The present study aims to develop a new scaffold and controlled release system for RSV with favourable properties for bone tissue engineering (BTE). In this experimental study, high porous polycaprolactone (PCL)-gelatin scaffolds that contained different concentrations of RSV (0 mg/10 ml, 0.1 mg/10 ml, 0.5 mg/10 ml, 2.5 mg/10 ml, 12.5 mg/10 ml, and 62.5 mg/10 ml) were fabricated by the thermally-induced phase separation (TIPS) method. Mechanical and biological properties of the scaffolds were evaluated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), compressive strength, porosity, MTT, alkaline phosphatase (ALP) activity, water contact angle, degradation rate, pH alteration, blood clotting index (BCI), and hemocompatibility. SEM analysis confirmed that the porous structure of the scaffolds contained interconnected pores. FTIR results showed that the RSV structure was maintained during the scaffold's fabrication. RSV (up to 62.5 mg/10 ml) increased compressive strength (16.342 ± 1.79 MPa), wettability (70.2), and degradation rate of the scaffolds. Scaffolds that contained 2.5 mg/10 ml RSV had the best effect on the human umbilical cord mesenchymal stem cell (HUC-MSCs) survival, hemocompatibility, and BCI. As a sustained release system, only 31.68 ± 0.1% of RSV was released from the PCL-Gelatin-2.5 mg/10 ml RSV scaffold over 30 days. In addition, the results of ALP activity showed that RSV increased the osteogenic differentiation potential of the scaffolds. PCL-Gelatin-2.5 mg/10 ml RSV scaffolds have favorable mechanical, physical, and osteogenic properties for bone tissue and provide a favorable release system for RSV. They can mentioned as a a promising strategy for bone regeneration that should be further assessed in animals and clinical studies.

Tuning the properties of all natural polymeric scaffolds for tendon repair with cellulose microfibers

Rotator cuff injuries affect a large percentage of the population worldwide. Surgical repair has rates of failure of up to 70%, and existing materials used in the reinforcement of injuries often lack appropriate mechanical properties and biodegradability. There is a clinical need for tendon biomaterials that enable cell attachment and proliferation, while supporting mechanically the injury site. In this work, we develop a novel all-natural polymeric scaffold for applications in the supraspinatus tendon of the shoulder. The unidirectional freezing technique is applied to a chitosan-gelatine matrix containing varying cellulose concentrations, followed by crosslinking with genipin. The viability of the technique using a custom 3D printed mould is evaluated. The scaffolds' morphology and mechanical properties are extensively characterized: the ultimate tensile strength of the material with 20% cellulose was found to increase 6-fold compared to scaffolds without cellulose; significant effects on the microstructure of the scaffold were evidenced via scanning electron microscopy. Furthermore, the biocompatibility of the materials was characterized with both porcine tendon derived cells and normal human dermal fibroblasts. All scaffolds are highly biocompatible, the incorporation of cellulose results in higher cell metabolic activity values and density of cells on the surface of the material. Scaffolds containing 20% cellulose fibers were found to possess the optimal biomechanical properties for applications in rotator cuff tendon repair.

A hydrogel derived from skin secretion of Andrias davidianus to facilitate bone regeneration

Bone regeneration relies heavily on balancing osteogenesis and osteoclastogenesis. Meeting the challenge of creating bone repair scaffolds with dual functionalities has long been elusive in bone tissue engineering. This study addresses these challenges through the utilization of a unique hydrogel that capitalizes on the dynamics of disulfide bonding to convert the skin secretion of Andrias davidianus (SSAD) into hydrolysate. This hydrolysate serves as the foundation for the construction of a novel SSAD protein hydrogel for bone regeneration, achieved through a photo-redox reaction under visible light crosslinking. The innovative SSAD protein hydrogel not only exhibits exceptional biocompatibility but also significantly enhances bone mineralization and angiogenesis in vitro. RNA sequencing delves into the underlying mechanisms governing the regulation of osteogenesis and osteoclastogenesis by the hydrogel. In vivo experiments conclusively demonstrate the potential of the SSAD protein hydrogel. It expedites vascularization within the defect area and synergistically facilitates the repair of bone defects. Furthermore, the SSAD hydrogel exhibits notable antimicrobial properties, effectively reducing the risk of implant-related infections in vivo. In summary, this research introduces a valuable and promising method for fabricating protein biomaterials that contribute to bone repair by promoting both bone and blood vessel growth while simultaneously inhibiting osteoclast formation.

Biomimetic mineralization of platelet lysate/oxidized dextran cryogel as a macroporous 3D composite scaffold for bone repair

Scaffold development approaches using autologous sources for tissue repair are of great importance in obtaining bio-active/-compatible constructs. Platelet-rich plasma (PRP) containing various growth factors and platelet lysate (PL) derived from PRP are autologous products that have the potential to accelerate the tissue repair response by inducing a transient inflammatory event. Considering the regenerative capacity of PRP and PL, PRP/PL-based scaffolds are thought to hold great promise for tissue engineering as a natural source of autologous growth factors and a provider of mechanical support for cells. Here, a bio-mineralized PRP-based scaffold was developed using oxidized dextran (OD) and evaluated for future application in bone tissue engineering. Prepared PL/OD scaffolds were incubated in simulated body fluid (SBF) for 7, 14 and 21 d periods. Mineralized PL/OD scaffolds were characterized using Fourier transform infrared spectroscopy, x-ray diffraction spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis, porosity and compression tests. SEM and energy-dispersive x-ray spectroscopy analyses revealed mineral accumulation on the PL/OD scaffold as a result of SBF incubation. In vitro cytotoxicity and in vitro hemolysis tests revealed that the scaffolds were non-toxic and hemocompatible. Additionally, human osteoblasts (hOBs) exhibited good attachment and spreading behavior on the scaffolds and maintained their viability throughout the culture period. The alkaline phosphatase activity assay and calcium release results revealed that PL/OD scaffolds preserved the osteogenic properties of hOBs. Overall, findings suggest that mineralized PL/OD scaffold may be a promising scaffold for bone tissue engineering.

Injectable and Microporous Microgel Assembly with Sequential Bioactive Factor Release for the Endogenous Repair of Nucleus Pulposus

AbstractHarnessing endogenous stem/progenitor cells to enhance extracellular matrix (ECM) deposition in the nucleus pulposus (NP) is considered as a potential treatment for intervertebral disc degeneration (IVDD), but is limited by the lack of suitable scaffolds for cell infiltration and growth, as well as the tailored release of bioactive factors. Herein, an injectable cell‐free microgel assembly (MA‐TNS) with interconnected microporous structure is developed to recruit stem/progenitor cells and induce the differentiation of the recruited cells by releasing stromal cell‐derived factor‐1α (SDF‐1α) and transforming growth factor‐β1 (TGF‐β1) sequentially. TGF‐β1 is initially loaded by the chondroitin sulfate/gelatin nanoparticles. Together with SDF‐1α, these nanoparticles are co‐encapsulated into the photo‐cross‐linked microgels, which are then assembled into a microporous scaffold via dynamic boronate ester bonds. An initial rapid release of SDF‐1α followed by a sustained release of TGF‐β1 lasting over 28 days is achieved. MA‐TNS significantly promotes the recruitment, infiltration, and chondrocyte‐like differentiation of marrow mesenchymal stem cells in vitro. Furthermore, in vivo experiments on rats and cynomolgus monkeys prove that MA‐TNS can inhibit IVDD and recover ECM deposition markedly, thereby enabling long‐term NP reconstruction. The resulting efficacy in rats and nonhuman primates supports that MA‐TNS is a promising scaffold for intervertebral disc repair and regeneration.

Bone morphogenetic protein-2 and pulsed electrical stimulation synergistically promoted osteogenic differentiation on MC-3T3-E1 cells.

Electrical stimulation (ES) plays an important role in regulating cell osteoblast differentiation. As a noninvasive rehabilitation therapy method, Es has a unique role in postoperative recovery. Bone morphogenetic protein-2 (BMP-2) is the most commonly used bioactive molecule in in situ tissue engineering scaffolds, and it plays an important regulatory role in the whole process of bone injury repair. In this study, the osteogenic regulation of MC-3T3-E1 cells was studied by combining pulsed electrical stimulation (PES) and different concentrations of BMP-2. The results showed that PES and BMP-2 could synergically promote the proliferation of MC-3T3-E1 cells. The qPCR results of osteoblast-related genes showed that PES was synergistic with BMP-2 to promote osteoblast differentiation mainly through the regulation of the Smad/BMP and insulin like growth factor 1 (IGF1) signaling pathways. The expression level of alkaline phosphatase (ALP) and alizarin red staining further demonstrated the synergistic effect of PES and BMP-2 on promoting osteogenic differentiation and mineralization of cells. PES and BMP-2 could also synergically promote cell proliferation, expression of collagen I (COL-I) and ALP, and cell mineralization on the 3D-printed polylactic acid scaffold. These results suggest that the use of PES can enhance the osteogenic effect of in situ bone repair scaffolds containing BMP-2, reduce the dose of BMP-2 alone, and reduce the possible side effects of high-dose BMP-2 in vivo.

Functionalized 3D Hydroxyapatite Scaffold by Fusion Peptides-Mediated Small Extracellular Vesicles of Stem Cells for Bone Tissue Regeneration.

3D printing technology offers extensive applications in tissue engineering and regenerative medicine (TERM) because it can create a three-dimensional porous structure with acceptable porosity and fine mechanical qualities that can mimic natural bone. Hydroxyapatite (HA) is commonly used as a bone repair material due to its excellent biocompatibility and osteoconductivity. Small extracellular vesicles (sEVs) derived from bone marrow mesenchymal stem cells (BMSCs) can regulate bone metabolism and stimulate the osteogenic differentiation of stem cells. This study has designed a functionalized bone regeneration scaffold (3D H-P-sEVs) by combining the biological activity of BMSCs-sEVs and the 3D-HA scaffold to improve bone regeneration. The scaffold utilizes the targeting of fusion peptides to increase the loading efficiency of sEVs. The composition, structure, mechanical properties, and in vitro degradation performance of the 3D H-P-sEVs scaffolds were examined. The composite scaffold demonstrated good biocompatibility, substantially increased the expression of osteogenic-related genes and proteins, and had a satisfactory bone integration effect in the critical skull defect model of rats. In conclusion, the combination of EVs and 3D-HA scaffold via fusion peptide provides an innovative composite scaffold for bone regeneration and repair, improving osteogenic performance.

Silicon and gadolinium co-doped hydroxyapatite/PLGA scaffolds with osteoinductive and MRI dual functions.

Introduction: An ideal bone repair scaffold should have dual functions of osteoinductive ability and in vivo imaging. In this study, the simultaneous substitution of silicon (Si) and gadolinium (Gd) in hydroxyapatite (HA) as potential multifunctional bone graft materials has been successfully developed. Methods: A series of HA nanoparticles (HA NPs) doped with different proportions of Si and Gd were prepared. The chemical structure and phase composition of the materials were analyzed using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The microstructure, magnetic properties, surface potential, and cytotoxicity of the materials were also analyzed. The magnetic resonance imaging (MRI) effect of Gd&Si-HA/poly(lactic-co-glycolic acid) (Gd&Si-HA/PLGA) composite materials was evaluated. Osteogenic-related gene expression, alkaline phosphatase (ALP) level, and mineralization capacity of MC3T3-E1 cultured on Gd&Si-HA/PLGA composite materials were also detected. Results and Discussion: The 1.5Gd&Si-HA@PLGA group showed good ability to promote osteogenic differentiation of cells. The MRI effect of the 1.5Gd&Si-HA@PLGA scaffold was observable. This HA material containing Si and Gd co-doping has a broad application prospect in the field of bone tissue engineering owing to its ability to enhance osteoinductive property and improve MRI effect.

The effects of heat and hydrogen peroxide treatment on the osteoinductivity of demineralized cortical bone: a potential method for preparing tendon/ligament repair scaffolds.

Recent studies have indicated that demineralized cortical bone (DCB) may be used to repair tendons and ligaments, such as the patellar tendon and anterior cruciate ligament (ACL). Hydrogen peroxide (H2O2) has been shown to reduce the osteoinductivity of DCB, and heat treatment may also decrease the osteoinductivity of DCB. The purpose of this study was (i) to determine whether heat treatment reduces the osteoinductivity of DCB and (ii) to compare the effectiveness of heat treatment and H2O2 treatment on BMP-2 inactivation. DCB was prepared by immersion in 0.6 N hydrochloric acid, and DCB-H and DCB-HO were prepared by heat treatment (70°C for 8 h) and H2O2 treatment (3% H2O2 for 8 h), respectively. The surface topographies, elemental distributions and histological structures of the scaffolds were observed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and histological staining. The viability and osteogenic differentiation of TDSCs cultured on the scaffolds were evaluated via live/dead cell staining and Cell Counting Kit-8 (CCK-8) testing, real-time polymerase chain reaction (RT-PCR) and western bolt (WB) analysis, alkaline phosphatase activity (ALP) and alizarin red S (ARS) staining. The intramuscular implantation of the scaffolds in rats was also used to evaluate the effect of heat treatment and H2O2 treatment on the osteoinductivity of DCB. Our results demonstrated that both treatments removed BMP-2 and osteocalcin (OCN) within the DCB and that DCB-H and DCB-HO had good cytocompatibility and reduced the osteogenic differentiation of TDSCs. Moreover, the in vivo results indicated that the DCB-H and DCB-HO groups had smaller areas of osteoid formation than did the DCB group, and the DCB-HO group had the smallest area among the three groups. Our study demonstrated that heat treatment could reduce the osteoinductivity of DCB, and that H2O2 treatment was more effective than heat treatment.

Application of metal-organic frameworks-based functional composite scaffolds in tissue engineering.

With the rapid development of materials science and tissue engineering, a variety of biomaterials have been used to construct tissue engineering scaffolds. Due to the performance limitations of single materials, functional composite biomaterials have attracted great attention as tools to improve the effectiveness of biological scaffolds for tissue repair. In recent years, metal-organic frameworks (MOFs) have shown great promise for application in tissue engineering because of their high specific surface area, high porosity, high biocompatibility, appropriate environmental sensitivities and other advantages. This review introduces methods for the construction of MOFs-based functional composite scaffolds and describes the specific functions and mechanisms of MOFs in repairing damaged tissue. The latest MOFs-based functional composites and their applications in different tissues are discussed. Finally, the challenges and future prospects of using MOFs-based composites in tissue engineering are summarized. The aim of this review is to show the great potential of MOFs-based functional composite materials in the field of tissue engineering and to stimulate further innovation in this promising area.

3D-printed PCL@BG scaffold integrated with SDF-1α-loaded hydrogel for enhancing local treatment of bone defects

BackgroundThe long-term nonunion of bone defects is always a difficult problem in orthopaedics treatment. Artificial bone implants made of polymeric materials are expected to solve this problem due to their suitable degradation rate and good biocompatibility. However, the lack of mechanical strength, low osteogenic induction ability and poor hydrophilicity of these synthetic polymeric materials limit their large-scale clinical application.ResultsIn this study, we used bioactive glass (BG) (20%, W/W) and polycaprolactone (PCL, 80%, W/W) as raw materials to prepare a bone repair scaffold (PCL@BG20) using fused deposition modelling (FDM) three-dimensional (3D) printing technology. Subsequently, stromal cell-derived factor-1α (SDF-1α) chemokines were loaded into the PCL@BG20 scaffold pores with gelatine methacryloyl (GelMA) hydrogel. The experimental results showed that the prepared scaffold had a porous biomimetic structure mimicking that of cancellous bone, and the compressive strength (44.89 ± 3.45 MPa) of the scaffold was similar to that of cancellous bone. Transwell experiments showed that scaffolds loaded with SDF-1α could promote the recruitment of bone marrow stromal cells (BMSCs). In vivo data showed that treatment with scaffolds containing SDF-1α and BG (PCL@BG-GelMA/SDF-1α) had the best effect on bone defect repair compared to the other groups, with a large amount of new bone and mature collagen forming at the bone defect site. No significant organ toxicity or inflammatory reactions were observed in any of the experimental groups.ConclusionsThe results show that this kind of scaffold containing BG and SDF-1α serves the dual functions of recruiting stem cell migration in vivo and promoting bone repair in situ. We envision that this scaffold may become a new strategy for the clinical treatment of bone defects.

A Ti3C2 MXene-integrated near-infrared-responsive multifunctional porous scaffold for infected bone defect repair.

Infected bone defect repair has long been a major challenge in orthopedic surgery. Apart from bacterial contamination, excessive generation of reactive oxygen species (ROS), and lack of osteogenesis ability also threaten the defect repair process. However, few strategies have been proposed to address these issues simultaneously. Herein, we designed and fabricated a near-infrared (NIR)-responsive, hierarchically porous scaffold to address these limitations in a synergetic manner. In this design, polymethyl methacrylate (PMMA) and polyethyleneimine (PEI) were used to fabricate the porous PMMA/PEI scaffolds via the anti-solvent vapor-induced phase separation (VIPS) process. Then, Ti3C2 MXenes were anchored on the scaffolds through the dopamine-assisted co-deposition process to obtain the PMMA/PEI/polydopamine (PDA)/MXene scaffolds. Under NIR laser irradiation, the scaffolds were able to kill bacteria through the direct contact-killing and synergetic photothermal effect of Ti3C2 MXenes and PDA. Moreover, MXenes and PDA also endowed the scaffolds with excellent ROS-scavenging capacity and satisfying osteogenesis ability. Our experimental results also confirmed that the PMMA/PEI/PDA/MXene scaffolds significantly promoted new bone formation in an infected mandibular defect model. We believe that our study provides new insights into the treatment of infected bone defects.

A 3D printable gelatin methacryloyl/chitosan hydrogel assembled with conductive PEDOT for neural tissue engineering

In neural tissue engineering, biomaterial scaffolds that have high conductivity and customized structures are crucial in promoting nerve regeneration. Poly(3,4-ethylenedioxythiophene) (PEDOT) has emerged as a promising conductive polymer with excellent chemical stability and biocompatibility. However, traditional three-dimensional (3D) printing of PEDOT-based conductive scaffolds faces challenges in limited printing resolution, poor solubility, and brittleness of conductive materials. Herein, digital light processing (DLP) printing was used to fabricate complex hydrogel structures using gelatin methacryloyl (GelMA) and chitosan (CS) while incorporating PEDOT nanoparticles through interfacial polymerization to create conducting pathways within a hydrogel structure. The integration of PEDOT significantly enhanced the electrical conductivity and mechanical properties of the GelMA/CS hydrogel while preserving printed details. The GelMA/CS-PEDOT hydrogel promoted cell proliferation and facilitated axon outgrowth of PC12 cells and Schwann cells during in vitro culture. Moreover, in vitro direct current electrical stimulation promoted axon elongation of PC12 cells cultured on a conductive substrate. In vivo studies used a conductive nerve conduit to repair a 10-mm rat sciatic nerve defect, validating the efficacy of GelMA/CS-PEDOT scaffold in peripheral nerve injury repair. These findings highlight the significant potential of conductive GelMA/CS-PEDOT hydrogel in the field of neural tissue engineering.

Cell-Derived Matrix: Production, Decellularization, and Application of Wound Repair.

Chronic nonhealing wounds significantly reduce patients' quality of life and are a major burden on healthcare systems. Over the past few decades, tissue engineering materials have emerged as a viable option for wound healing, with cell-derived extracellular matrix (CDM) showing remarkable results. The CDM's compatibility and resemblance to the natural tissue microenvironment confer distinct advantages to tissue-engineered scaffolds in wound repair. This review summarizes the current processes for CDM preparation, various cell decellularization protocols, and common characterization methods. Furthermore, it discusses the applications of CDM in wound healing, including skin defect and wound repair, angiogenesis, and engineered vessels, and offers perspectives on future developments.

A responsive cascade drug delivery scaffold adapted to the therapeutic time window for peripheral nerve injury repair.

Peripheral nerve injury (PNI) is a common clinical challenge, requiring timely and orderly initiation of synergistic anti-inflammatory and reparative therapy. Although the existing cascade drug delivery system can realize sequential drug release through regulation of the chemical structure of drug carriers, it is difficult to adjust the release kinetics of each drug based on the patient's condition. Therefore, there is an urgent need to develop a cascade drug delivery system that can dynamically adjust drug release and realize personalized treatment. Herein, we developed a responsive cascade drug delivery scaffold (RCDDS) which can adapt to the therapeutic time window, in which Vitamin B12 is used in early controllable release to suppress inflammation and nerve growth factor promotes regeneration by cascade loading. The RCDDS exhibited the ability to modulate the drug release kinetics by hierarchically opening polymer chains triggered by ultrasound, enabling real-time adjustment of the anti-inflammatory and neuroregenerative therapeutic time window depending on the patient's status. In the rat sciatic nerve injury model, the RCDDS group was able to achieve neural repair effects comparable to the autograft group in terms of tissue structure and motor function recovery. The development of the RCDDS provides a useful route toward an intelligent cascade drug delivery system for personalized therapy.