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Graphene oxide (GO), a carbon-based nanomaterial, presents significant potential across biomedical fields such as bioimaging, drug delivery, biosensors, and phototherapy. This study examines the effects of integrating GO into poly(lactic-co-glycolic acid) (PLGA) scaffolds on human immune cell function. Our results demonstrate that high concentrations of GO reduce the viability of peripheral blood mononuclear cells (PBMCs) following stimulation with anti-CD3 antibody. This reduction extends to T lymphocyte activation, evident from the diminished proliferative response to T cell receptor engagement and impaired differentiation into T helper subsets and regulatory T cells. Interestingly, although GO induces a minimal response in resting monocytes, but it significantly affects both the viability and the differentiation potential of monocytes induced to mature toward M1 pro-inflammatory and M2-like immunoregulatory macrophages. This study seeks to address a critical gap by investigating the in vitro immunomodulatory effects of PLGA scaffolds incorporating various concentrations of GO on primary immune cells, specifically PBMCs isolated from healthy donors. Our findings emphasize the need to optimize the GO to PLGA ratios and scaffold design to advance PLGA-GO-based biomedical applications. STATEMENT OF SIGNIFICANCE: Graphene oxide (GO) holds immense promise for biomedical applications due to its unique properties. However, concerns regarding its potential to trigger adverse immune responses remain. This study addresses this critical gap by investigating the in vitro immunomodulatory effects of PLGA scaffolds incorporating increasing GO concentrations on human peripheral blood mononuclear cells (PBMCs). By elucidating the impact on cell viability, T cell proliferation and differentiation, and the maturation/polarization of antigen-presenting cells, this work offers valuable insights for designing safe and immunologically compatible GO-based biomaterials for future clinical translation.
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Grafito , Leucocitos Mononucleares , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Andamios del Tejido , Grafito/química , Grafito/farmacología , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Andamios del Tejido/química , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Monocitos/efectos de los fármacos , Monocitos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunologíaRESUMEN
Commercially available bioactive glasses (BAGs) are exclusively used in powder form, due to their tendency to crystallize. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. This study investigates the potential of 1393B20 scaffolds to support bone regeneration and mineralization in vitro and in vivo, in comparison to silicate 1393. Both scaffolds supported human adipose stem cells proliferation, either in direct contact for the 1393, or mainly around for the 1393B20. Similarly, both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. In addition, these scaffolds supported bone regeneration and osteoclast/osteoblast activity in vivo in critical-sized rat calvarial defect. Nevertheless, mineralization and collagen formation were significantly enhanced for the 1393B20, at 3-months post-implantation, assigned to faster and more complete dissolution of the scaffolds. Thus, 1393B20 demonstrates greater promise for bone tissue engineering certainly due to its time-controlled release of boron and silicon. STATEMENT OF SIGNIFICANCE: Bioactive glasses (BAGs) show great promise in bone tissue engineering as they effectively bond with bone tissue, fostering integration and regeneration. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. Both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. The presence of boron in the 1393B20 enhanced mineralization and collagen formation in vivo compared to 1393, probably due to its faster dissolution rate. Here, 1393B20 demonstrated greater promise for bone tissue engineering compared to the well-known 1393 BAG.
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Regeneración Ósea , Boro , Diferenciación Celular , Vidrio , Osteogénesis , Silicatos , Andamios del Tejido , Andamios del Tejido/química , Silicatos/química , Silicatos/farmacología , Regeneración Ósea/efectos de los fármacos , Animales , Vidrio/química , Boro/química , Boro/farmacología , Humanos , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ratas , Masculino , Células Madre/citología , Células Madre/metabolismo , Ratas Sprague-Dawley , Ratas WistarRESUMEN
Bone tissue engineering (BTE) aims to promote bone regeneration by means of the synergistic effect of biomaterials, cells, and other factors, as potential alternative to conventional treatments for bone fractures. To this aim, a composite material was developed, based on collagen type I, strontium-enriched mesoporous bioactive glasses, and hydroxyapatite nanorods as bioactive and biomimetic components. Nanostructured scaffolds were 3D printed and subsequently chemically crosslinked with genipin to improve mechanical properties and stability. The developed nanostructured system was maintained in culture until 3 weeks with a co-culture of human bone cells to provide anex vivomodel of bone microenvironment and examine the cellular crosstalk and signaling pathways through paracrine cell activities. Human osteoblasts (OBs), derived from trabecular bone, and human osteoclast precursors (OCs), isolated from buffy coat samples were involved, with OBs seeded on the scaffold and OC precursors seeded in a transwell device. When compared to the material without inorganic components, the bioactive and biomimetic scaffold positively influenced cell proliferation and cell metabolic activity, boosting alkaline phosphatase activity of OBs, and reducing OC differentiation. Thus, the bioactive and biomimetic system promoted an enhanced cellular response, highlighting its potential application in BTE.
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Materiales Biocompatibles , Diferenciación Celular , Proliferación Celular , Durapatita , Nanotubos , Osteoblastos , Osteoclastos , Impresión Tridimensional , Estroncio , Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Humanos , Andamios del Tejido/química , Estroncio/química , Osteoblastos/citología , Osteoclastos/citología , Osteoclastos/metabolismo , Durapatita/química , Nanotubos/química , Diferenciación Celular/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Vidrio/química , Huesos/metabolismo , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Colágeno/química , Técnicas de Cocultivo , Células Cultivadas , Fosfatasa Alcalina/metabolismo , IridoidesRESUMEN
Inflammatory responses play a central role in coordinating biomaterial-mediated tissue regeneration. However, precise modulation of dynamic variations in microenvironmental inflammation post-implantation remains challenging. In this study, the traditional ß-tricalcium phosphate-based scaffold is remodeled via ultrathin MXene-Ti3C2 decoration and Zn2+/Sr2+ ion-substitution, endowing the scaffold with excellent reactive oxygen species-scavenging ability, near-infrared responsivity, and enhanced mechanical properties. The induction of mild hyperthermia around the implant via periodic near-infrared irradiation facilitates spatiotemporal regulation of inflammatory cytokines secreted by a spectrum of macrophage phenotypes. The process initially amplifies the pro-inflammatory response, then accelerates M1-to-M2 macrophage polarization transition, yielding a satisfactory pattern of osteo-immunomodulation during the natural bone healing process. Later, sustained release of Zn2+/Sr2+ ions with gradual degradation of the 3D scaffold maintains the favorable reparative M2-dominated immunological microenvironment that supports new bone mineralization. Precise temporal immunoregulation of the bone healing process by the intelligent 3D scaffold enhances bone regeneration in a rat cranial defect model. This strategy paves the way for the application of ß-tricalcium phosphate-based materials to guide the dynamic inflammatory and bone tissue responses toward a favorable outcome, making clinical treatment more predictable and durable. The findings also demonstrate that near-infrared irradiation-derived mild hyperthermia is a promising method of immunomodulation.
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When treating orthopaedic damage or illness and accidental fracture, bone grafting remains the gold standard of treatment. In cases where this approach does not seem achievable, bone tissue engineering can offer scaffolding as a substitute. Defective and fractured bone tissue is extracted and substituted with porous scaffold structures to aid in the process of tissue regeneration. 3D bioprinting has demonstrated enormous promise in recent years for producing scaffold structures with the necessary capabilities. In order to create composite biomaterial inks for 3D bioprinting, three different materials were combined such as silk fibroin, bone particles, and synthetic biopolymer poly (ε-caprolactone) (PCL). These biomaterials were used to fabricate the two composites scaffolds such as: silk fibroin + bovine bone (SFB) and silk fibroin + bovine bone + Polycaprolactone (SFBP). The biomechanical, structural, and biological elements of the manufactured composite scaffolds were characterized in order to determine their suitability as a possible biomaterial for the production of bone tissue. The in vitro bioactivity of the two composite scaffolds was assessed in the simulated body fluids, and the swelling and degradation characteristics of the two developed scaffolds were analyzed separately over time. The results showed that the mechanical durability of the composite scaffolds was enhanced by the bovine bone particles, up to a specific concentration in the silk fibroin matrix. Furthermore, the incorporation of bone particles improved the bioactive composite scaffolds' capacity to generate hydroxyapatite in vitro. The combined findings show that the two 3D printed bio-composites scaffolds have the required mechanical strength and may be applied to regeneration of bone tissue and restoration, since they resemble the characteristics of native bone.
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Materiales Biocompatibles , Fibroínas , Ensayo de Materiales , Impresión Tridimensional , Andamios del Tejido , Fibroínas/química , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Bovinos , Andamios del Tejido/química , Huesos/cirugía , Fenómenos Mecánicos , Poliésteres/química , Pruebas Mecánicas , Prótesis e ImplantesRESUMEN
The in vitro evaluation of 3D scaffolds for bone tissue engineering in mono-cultures is a common practice; however, it does not represent the native complex nature of bone tissue. Co-cultures of osteoblasts and osteoclasts, without the addition of stimulating agents for monitoring cellular cross-talk, remains a challenge. In this study, a growth factor-free co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and human peripheral blood mononuclear cells (hPBMCs) has been established and used for the evaluation of 3D-printed scaffolds for bone tissue engineering. The scaffolds were produced from PLLA/PCL/PHBV polymeric blends, with two composite materials produced through the addition of 2.5% w/v nanohydroxyapatite (nHA) or strontium-substituted nanohydroxyapatite (Sr-nHA). Cell morphology data showed that hPBMCs remained undifferentiated in co-culture, while no obvious differences were observed in the mono- and co-cultures of hBM-MSCs. A significantly increased alkaline phosphatase (ALP) activity and osteogenic gene expression was observed in co-culture on Sr-nHA-containing scaffolds. Tartrate-resistant acid phosphatase (TRAP) activity and osteoclastogenic gene expression displayed significantly suppressed levels in co-culture on Sr-nHA-containing scaffolds. Interestingly, mono-cultures of hPBMCs on Sr-nHA-containing scaffolds indicated a delay in osteoclasts formation, as evidenced from TRAP activity and gene expression, demonstrating that strontium acts as an osteoclastogenesis inhibitor. This co-culture study presents an effective 3D model to evaluate the regenerative capacity of scaffolds for bone tissue engineering, thus minimizing time-consuming and costly in vivo experiments.
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Introduction: Bone defects remain a thorny challenge that clinicians have to face. At present, scaffolds prepared by 3D printing are increasingly used in the field of bone tissue repair. Polylactic acid (PLA) has good thermoplasticity, processability, biocompatibility, and biodegradability, but the PLA is brittle and has poor osteogenic performance. Beta-tricalcium phosphate (ß-TCP) has good mechanical properties and osteogenic induction properties, which can make up for the drawbacks of PLA. Methods: In this study, photocurable biodegradable polylactic acid (bio-PLA) was utilized as the raw material to prepare PLA/ß-TCP slurries with varying ß-TCP contents (ß-TCP dosage at 0%, 10%, 20%, 30%, 35% of the PLA dosage, respectively). The PLA/ß-TCP scaffolds were fabricated using liquid crystal display (LCD) light-curing 3D printing technology. The characterization of the scaffolds was assessed, and the biological activity of the scaffold with the optimal compressive strength was evaluated. The biocompatibility of the scaffold was assessed through CCK-8 assays, hemocompatibility assay and live-dead staining experiments. The osteogenic differentiation capacity of the scaffold on MC3T3-E1 cells was evaluated through alizarin red staining, alkaline phosphatase (ALP) detection, immunofluorescence experiments, and RT-qPCR assays. Results: The prepared scaffold possesses a three-dimensional network structure, and with an increase in the quantity of ß-TCP, more ß-TCP particles adhere to the scaffold surface. The compressive strength of PLA/ß-TCP scaffolds exhibits a trend of initial increase followed by decrease with an increasing amount of ß-TCP, reaching a maximum value of 52.1 MPa at a 10% ß-TCP content. Degradation rate curve results indicate that with the passage of time, the degradation rate of the scaffold gradually increases, and the pH of the scaffold during degradation shows an alkaline tendency. Additionally, Live/dead staining and blood compatibility experiments suggest that the prepared PLA/ß-TCP scaffold demonstrates excellent biocompatibility. CCK-8 experiments indicate that the PLA/ß-TCP group promotes cell proliferation, and the prepared PLA/ß-TCP scaffold exhibits a significant ability to enhance the osteogenic differentiation of MC3T3-E1 cells in vitro. Discussion: 3D printed LCD photocuring PLA/ß-TCP scaffolds could improve surface bioactivity and lead to better osteogenesis, which may provide a unique strategy for developing bioactive implants in orthopedic applications.
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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.
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Osteogénesis , Andamios del Tejido , Animales , Conejos , Regeneración Ósea , Durapatita/farmacología , Impresión TridimensionalRESUMEN
Surgically addressing tumors poses a challenge, requiring a tailored, multidisciplinary approach for each patient based on the unique aspects of their case. Innovative therapeutic regimens combined to reliable reconstructive methods can contribute to an extended patient's life expectancy. This study presents a detailed comparative investigation of near-infrared therapy protocols, examining the impact of non-fractionated and fractionated irradiation regimens on cancer treatment. The therapy is based on the implantation of graphene oxide/poly(lactic-co-glycolic acid) three-dimensional printed scaffolds, exploring their versatile applications in oncology by the examination of pro-inflammatory cytokine secretion, immune response, and in vitro and in vivo tumor therapy. The investigation into cell death patterns (apoptosis vs necrosis) underlines the pivotal role of protocol selection underscores the critical influence of treatment duration on cell fate, establishing a crucial parameter in therapeutic decision-making. In vivo experiments corroborated the profound impact of protocol selection on tumor response. The fractionated regimen emerged as the standout performer, achieving a substantial reduction in tumor size over time, surpassing the efficacy of the non-fractionated approach. Additionally, the fractionated regimen exhibited efficacy also in targeting tumors in proximity but not in direct contact to the scaffolds. Our results address a critical gap in current research, highlighting the absence of a standardized protocol for optimizing the outcome of photodynamic therapy. The findings underscore the importance of personalized treatment strategies in achieving optimal therapeutic efficacy for precision cancer therapy.
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In the burgeoning domain of orthopedic therapeutic research, Platelet-Rich Plasma (PRP) has firmly established its position, transforming paradigms ranging from tissue regeneration to the management of chondral lesions. This review delves into PRP's recent integrations with cutting-edge interventions such as 3D-printed scaffolds, its role in bone and cartilage defect management, and its enhanced efficacy when combined with molecules like Kartogenin (KGN) for fibrocartilage zone repair. Significant attention is paid to tissue engineering for meniscal interventions, where a combination of KGN, PRP, and bone marrow-derived mesenchymal stem cells are under exploration. Within the sphere of osteochondral regenerative therapy, the synergy of PRP with Bone Marrow Aspirate Concentrate (BMAC) represents a noteworthy leap towards cartilage regeneration. The innovative incorporation of PRP with biomaterials like hydroxyapatite and graphene oxide further underscores its versatility in supporting structural integrity and ensuring sustained growth factor release. However, while PRP's autologous and nontoxic nature makes it an inherently safe option, concerns arising from its preparation methods, particularly with bovine thrombin, necessitate caution. As of 2023, despite the burgeoning promise of PRP in bone healing, the quest for its standardization, optimization, and substantiation through rigorous clinical trials continues. This comprehensive review elucidates the contemporary applications, challenges, and future trajectories of PRP in orthopedics, aiming to spotlight areas primed for further research and exploration.
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Procedimientos de Cirugía Plástica , Plasma Rico en Plaquetas , Humanos , Animales , Bovinos , Cicatrización de Heridas , Materiales Biocompatibles , Artrodesis , Plasma Rico en Plaquetas/química , Plasma Rico en Plaquetas/metabolismoRESUMEN
Current clinical treatment of periodontitis alleviates periodontal symptoms and helps to keep the disease under control for extended periods. Despite this, a significant destruction of the tooth's underlying bone tissue often takes place progressively. Herein, we present a two-way therapeutic approach for local delivery of antibacterial agents and bone tissue regeneration, incorporating ~1% w/w tetracycline hydrochloride (TCH) into a 3D-printed scaffold composed of poly(ε-caprolactone) (PCL). Samples were assessed for their morphological, physicochemical, pharmacokinetic, and antibacterial properties. Furthermore, osteoprecursor cells (MC3T3-E1) were employed to evaluate the osteoinductive potential of the drug-loaded scaffolds. Cell proliferation, viability, and differentiation were determined on all cell-seeded scaffolds. At the end of the culture, PCL-TCH scaffolds promoted abundant collagen organic matrix, demonstrating augmented alkaline phosphatase (ALP) activity and areas of accumulated mineralised bone tissue, despite their belayed cell proliferation. Based on the observed effectiveness of the PCL-TCH scaffolds to inhibit Staphylococcus aureus, these constructs could serve as an alternative bioactive implant that supports bacterial inhibition and favours a 3D microenvironment for bone tissue regeneration in severe periodontitis.
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Periodontitis , Andamios del Tejido , Humanos , Andamios del Tejido/química , Ingeniería de Tejidos , Osteogénesis , Poliésteres/química , Huesos , Antibacterianos/farmacología , Regeneración Ósea , Tetraciclina/farmacología , Periodontitis/tratamiento farmacológico , Impresión TridimensionalRESUMEN
Approximately 50% of the adult global population is projected to suffer from some form of metabolic disease by 2050, including metabolic syndrome and diabetes mellitus. At the same time, this trend indicates a potential increase in the number of patients who will be in need of implant-supported reconstructions of specific bone regions subjected to inflammatory states. Moreover, physiological conditions associated with dysmetabolic subjects have been suggested to contribute to the severity of bone loss after bone implant insertion. However, there is a perspective evidence strengthening the hypothesis that custom-fabricated bioengineered scaffolds may produce favorable bone healing effects in case of altered endocrine or metabolic conditions. This perspective review aims to share a comprehensive knowledge of the mechanisms implicated in bone resorption and remodelling processes, which have driven researchers to develop metallic implants as the cobalt-chromium (Co-Cr) bioscaffolds, presenting optimized geometries that interact in an effective way with the osteogenetic precursor cells, especially in the cases of perturbed endocrine or metabolic conditions.
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Current treatments for repairing articular cartilage defects are limited. However, pro-chondrogenic hydrogels formulated using articular cartilage matrix components (such as hyaluronic acid (HA) and collagen type II (Col II)), offer a potential solution if they could be injected into the defect via minimally invasive arthroscopic procedures, or used as bioinks to 3D print patient-specific customised regenerative scaffolds-potentially combined with cells. However, HA and Col II are difficult to incorporate into injectable/3D printable hydrogels due to poor physicochemical properties. This study aimed to overcome this by developing an articular cartilage matrix-inspired pro-chondrogenic hydrogel with improved physicochemical properties for both injectable and 3D printing (3DP) applications. To achieve this, HA was methacrylated to improve mechanical properties and mixed in a 1:1 ratio with Col I, a Col I/Col II blend or Col II. Col I possesses superior mechanical properties to Col II and so was hypothesised to enhance hydrogel mechanical properties. Rheological analysis showed that the pre-gels had viscoelastic and shear thinning properties. Subsequent physicochemical analysis of the crosslinked hydrogels showed that Col II inclusion resulted in a more swollen and softer polymer network, without affecting degradation time. While all hydrogels exhibited exemplary injectability, only the Col I-containing hydrogels had sufficient mechanical stability for 3DP applications. To facilitate 3DP of multi-layered scaffolds using methacrylated HA (MeHA)-Col I and MeHA-Col I/Col II, additional mechanical support in the form of a gelatin slurry support bath freeform reversible embedding of suspended hydrogels was utilised. Biological analysis revealed that Col II inclusion enhanced hydrogel-embedded MSC chondrogenesis, thus MeHA-Col II was selected as the optimal injectable hydrogel, and MeHA-Col I/Col II as the preferred bioink. In summary, this study demonstrates how tailoring biomaterial composition and physicochemical properties enables development of pro-chondrogenic hydrogels with potential for minimally invasive delivery to injured articular joints or 3DP of customised regenerative implants for cartilage repair.
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Cartílago Articular , Ácido Hialurónico , Humanos , Ácido Hialurónico/química , Cartílago Articular/metabolismo , Hidrogeles/farmacología , Hidrogeles/química , Colágeno Tipo II/metabolismo , Condrogénesis , Ingeniería de TejidosRESUMEN
Alveolar ridge augmentation is an important dental procedure to increase the volume of bone tissue in the alveolar ridge before the installation of a dental implant. To meet the high demand for bone grafts for alveolar ridge augmentation and to overcome the limitations of autogenous bone, allografts, and xenografts, researchers are developing bone grafts from synthetic materials using novel fabrication techniques such as 3D printing. To improve the clinical performance of synthetic bone grafts, stem cells with osteogenic differentiation capability can be loaded into the grafts. In this pilot study, we propose a novel bone graft which combines a 3D-printed polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold with adipose-derived mesenchymal stem cells (AD-MSCs) that can be harvested, processed and implanted within the alveolar ridge augmentation surgery. We evaluated the novel bone graft in a porcine lateral alveolar defect model. Radiographic analysis revealed that the addition of AD-MSCs to the PCL-TCP scaffold improved the bone volume in the defect from 18.6% to 28.7% after 3 months of healing. Histological analysis showed the presence of AD-MSCs in the PCL-TCP scaffold led to better formation of new bone and less likelihood of fibrous encapsulation of the scaffold. Our pilot study demonstrated that the loading of AD-MSCs improved the bone regeneration capability of PCL-TCP scaffolds, and our novel bone graft is suitable for alveolar ridge augmentation.
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Lactobacilli, play a beneficial role in the female reproductive tract (FRT), regulating pH via lactic acid metabolism to help maintain a healthy environment. Bacterial vaginosis (BV) is characterized by a dysregulated flora in which anaerobes such as Gardnerella vaginalis (Gardnerella) create a less acidic environment. Current treatment focuses on antibiotic administration, including metronidazole, clindamycin, or tinidazole; however, lack of patient compliance as well as antibiotic resistance may contribute to 50% recurrence within a year. Recently, locally administered probiotics such as Lactobacillus crispatus (L. crispatus) have been evaluated as a prophylactic against recurrence. To mitigate the lack of patient compliance, sustained probiotic delivery has been proposed via 3D-bioprinted delivery vehicles. Successful delivery depends on a variety of vehicle fabrication parameters influencing timing and rate of probiotic recovery; detailed evaluation of these parameters would benefit from computational modeling complementary to experimental evaluation. This study implements a novel simulation platform to evaluate sustained delivery of probiotics from 3D-bioprinted scaffolds, taking into consideration bacterial lactic acid production and associated pH changes. The results show that the timing and rate of probiotic recovery can be realistically simulated based on fabrication parameters that affect scaffold degradation and probiotic survival. Longer term, the proposed approach could help personalize localized probiotic delivery to the FRT to advance women's health.
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The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid-co-glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2 polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid-associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K-AKT signaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.
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Osteogénesis , Andamios del Tejido , Humanos , Ratas , Animales , Fosfatidilinositol 3-Quinasas/farmacología , Regeneración Ósea , Materiales Biocompatibles/farmacología , Impresión TridimensionalRESUMEN
Current standard wound care involves dressings that provide moisture and protection; however, dressings providing active healing are still scarce and expensive. We aimed to develop an ecologically sustainable 3D printed bioactive hydrogel-based topical wound dressing targeting healing of hard-to-heal wounds, such as chronic or burn wounds, which are low on exudate. To this end, we developed a formulation composed of renewable marine components; purified extract from unfertilized salmon roe (heat-treated X, HTX), alginate from brown seaweed, and nanocellulose from tunicates. HTX is believed to facilitate the wound healing process. The components were successfully formulated into a 3D printable ink that was used to create a hydrogel lattice structure. The 3D printed hydrogel showed a HTX release profile enhancing pro-collagen I alpha 1 production in cell culture with potential of promoting wound closure rates. The dressing has recently been tested on burn wounds in Göttingen minipigs and shows accelerated wound closure and reduced inflammation. This paper describes the dressings development, mechanical properties, bioactivity, and safety.
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Bone repair and tissue-engineering (BTE) approaches require novel biomaterials to produce scaffolds with required structural and biological characteristics and enhanced performances with respect to those currently available. In this study, PCL/INU-PLA hybrid biomaterial was prepared by blending of the aliphatic polyester poly(ε-caprolactone) (PCL) with the amphiphilic graft copolymer Inulin-g-poly(D,L)lactide (INU-PLA) synthetized from biodegradable inulin (INU) and poly(lactic acid) (PLA). The hybrid material was suitable to be processed using fused filament fabrication 3D printing (FFF-3DP) technique rendering macroporous scaffolds. PCL and INU-PLA were firstly blended as thin films through solvent-casting method, and then extruded by hot melt extrusion (HME) in form of filaments processable by FFF-3DP. The physicochemical characterization of the hybrid new material showed high homogeneity, improved surface wettability/hydrophilicity as compared to PCL alone, and right thermal properties for FFF process. The 3D printed scaffolds exhibited dimensional and structural parameters very close to those of the digital model, and mechanical performances compatible with the human trabecular bone. In addition, in comparison to PCL, hybrid scaffolds showed an enhancement of surface properties, swelling ability, and in vitro biodegradation rate. In vitro biocompatibility screening through hemolysis assay, LDH cytotoxicity test on human fibroblasts, CCK-8 cell viability, and osteogenic activity (ALP evaluation) assays on human mesenchymal stem cells showed favorable results.
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Ingeniería de Tejidos , Andamios del Tejido , Humanos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Inulina , Materiales Biocompatibles/química , Poliésteres/química , Impresión TridimensionalRESUMEN
Sustained vaginal administration of antibiotics or probiotics has been proposed to improve treatment efficacy for bacterial vaginosis. 3D printing has shown promise for development of systems for local agent delivery. In contrast to oral ingestion, agent release kinetics can be fine-tuned by the 3D printing of specialized scaffold designs tailored for particular treatments while enhancing dosage effectiveness via localized sustained release. It has been challenging to establish scaffold properties as a function of fabrication parameters to obtain sustained release. In particular, the relationships between scaffold curing conditions, compressive strength, and drug release kinetics remain poorly understood. This study evaluates 3D printed scaffold formulation and feasibility to sustain the release of metronidazole, a commonly used antibiotic for BV. Cylindrical silicone scaffolds were printed and cured using three different conditions relevant to potential future incorporation of temperature-sensitive labile biologics. Compressive strength and drug release were monitored for 14d in simulated vaginal fluid to assess long-term effects of fabrication conditions on mechanical integrity and release kinetics. Scaffolds were mechanically evaluated to determine compressive and tensile strength, and elastic modulus. Release profiles were fitted to previous kinetic models to differentiate potential release mechanisms. The Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin models best described the release, indicating similarity to release from insoluble or polymeric matrices. This study shows the feasibility of 3D printed silicone scaffolds to provide sustained metronidazole release over 14d, with compressive strength and drug release kinetics tuned by the fabrication parameters.
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Bone defect combined with drug-resistant bacteria-related infection is a thorny challenge in clinic. Herein, 3D-printed polyhydroxyalkanoates/ß-tricalcium phosphate (PHA/ß-TCP, PT) scaffolds were prepared by fused deposition modeling. Then copper-containing carboxymethyl chitosan/alginate (CA/Cu) hydrogels were integrated with the scaffolds via a facile and low-cost chemical crosslinking method. The resultant PT/CA/Cu scaffolds could promote not only proliferation but also osteogenic differentiation of preosteoblasts in vitro. Moreover, PT/CA/Cu scaffolds exhibited a strong antibacterial activity towards a broad-spectrum of bacteria including methicillin-resistant Staphylococcus aureus (MRSA) through inducing the intercellular generation of reactive oxygen species. In vivo experiments further demonstrated that PT/CA/Cu scaffolds significantly accelerated bone repair of cranial defects and efficiently eliminated MRSA-related infection, showing potential for application in infected bone defect therapy.