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1.
Cell Mol Neurobiol ; 44(1): 43, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38703332

RESUMEN

Cell transplantation is a promising treatment option for spinal cord injury (SCI). However, there is no consensus on the choice of carrier scaffolds to host the cells. This study aims to evaluate the efficacy of different material scaffold-mediated cell transplantation in treating SCI in rats. According to PRISMA's principle, Embase, PubMed, Web of Science, and Cochrane databases were searched, and relevant literature was referenced. Only original research on cell transplantation plus natural or synthetic scaffolds in SCI rats was included. Direct and indirect evidence for improving hind limb motor function was pooled through meta-analysis. A subgroup analysis of some factors that may affect the therapeutic effect was conducted to understand the results fully. In total, 25 studies met the inclusion criteria, in which 293 rats received sham surgery, 78 rats received synthetic material scaffolds, and 219 rats received natural materials scaffolds. The network meta-analysis demonstrated that although synthetic scaffolds were slightly inferior to natural scaffolds in terms of restoring motor function in cell transplantation of SCI rats, no statistical differences were observed between the two (MD: -0.35; 95% CI -2.6 to 1.9). Moreover, the subgroup analysis revealed that the type and number of cells may be important factors in therapeutic efficacy (P < 0.01). Natural scaffolds and synthetic scaffolds are equally effective in cell transplantation of SCI rats without significant differences. In the future, the findings need to be validated in multicenter, large-scale, randomized controlled trials in clinical practice. Trial registration: Registration ID CRD42024459674 (PROSPERO).


Asunto(s)
Trasplante de Células , Traumatismos de la Médula Espinal , Andamios del Tejido , Animales , Traumatismos de la Médula Espinal/terapia , Ratas , Andamios del Tejido/química , Trasplante de Células/métodos , Metaanálisis en Red , Resultado del Tratamiento , Recuperación de la Función
2.
Eur J Med Res ; 29(1): 270, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704575

RESUMEN

BACKGROUND: This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS: CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS: Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION: GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.


Asunto(s)
Cabello , Factor I del Crecimiento Similar a la Insulina , Células Madre Mesenquimatosas , Cordón Umbilical , Animales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Humanos , Medios de Cultivo Condicionados/farmacología , Ratones , Cordón Umbilical/citología , Cabello/crecimiento & desarrollo , Cabello/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Gelatina/química , Andamios del Tejido/química , Ratones Endogámicos C57BL , Células Cultivadas , Factor 7 de Crecimiento de Fibroblastos/metabolismo
3.
Biotechnol J ; 19(5): e2300734, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38719571

RESUMEN

Self-assembly of biological elements into biomimetic cargo carriers for targeting and delivery is a promising approach. However, it still holds practical challenges. We developed a functionalization approach of DNA origami (DO) nanostructures with neuronal growth factor (NGF) for manipulating neuronal systems. NGF bioactivity and its interactions with the neuronal system were demonstrated in vitro and in vivo models. The DO elements fabricated by molecular self-assembly have manipulated the surrounding environment through static spatially and temporally controlled presentation of ligands to the cell surface receptors. Our data showed effective bioactivity in differentiating PC12 cells in vitro. Furthermore, the DNA origami NGF (DON) affected the growth directionality and spatial capabilities of dorsal root ganglion neurons in culture by introducing a chemotaxis effect along a gradient of functionalized DO structures. Finally, we showed that these elements provide enhanced axonal regeneration in a rat sciatic nerve injury model in vivo. This study is a proof of principle for the functionality of DO in neuronal manipulation and regeneration. The approach proposed here, of an engineered platform formed out of programmable nanoscale elements constructed of DO, could be extended beyond the nervous system and revolutionize the fields of regenerative medicine, tissue engineering, and cell biology.


Asunto(s)
ADN , Ganglios Espinales , Factor de Crecimiento Nervioso , Regeneración Nerviosa , Animales , Ratas , Células PC12 , ADN/química , Ganglios Espinales/citología , Factor de Crecimiento Nervioso/química , Factor de Crecimiento Nervioso/farmacología , Nanoestructuras/química , Neuronas , Nervio Ciático , Andamios del Tejido/química , Ratas Sprague-Dawley
4.
Stem Cell Res Ther ; 15(1): 135, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715130

RESUMEN

BACKGROUND: Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. METHODS: The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. RESULTS: The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. CONCLUSIONS: The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.


Asunto(s)
Regeneración Ósea , Regeneración Ósea/efectos de los fármacos , Animales , Osteogénesis/efectos de los fármacos , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Ratones , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Membranas Artificiales , Regeneración Tisular Dirigida/métodos , Andamios del Tejido/química , Poliésteres/química , Poliésteres/farmacología , Ratas
5.
Sci Rep ; 14(1): 12171, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806547

RESUMEN

Upon implanting tissue-engineered heart valves (TEHVs), blood-derived macrophages are believed to orchestrate the remodeling process. They initiate the immune response and mediate the remodeling of the TEHV, essential for the valve's functionality. The exact role of another macrophage type, the tissue-resident macrophages (TRMs), has not been yet elucidated even though they maintain the homeostasis of native tissues. Here, we characterized the response of hTRM-like cells in contact with a human tissue engineered matrix (hTEM). HTEMs comprised intracellular peptides with potentially immunogenic properties in their ECM proteome. Human iPSC-derived macrophages (iMφs) could represent hTRM-like cells in vitro and circumvent the scarcity of human donor material. iMφs were derived and after stimulation they demonstrated polarization towards non-/inflammatory states. Next, they responded with increased IL-6/IL-1ß secretion in separate 3/7-day cultures with longer production-time-hTEMs. We demonstrated that iMφs are a potential model for TRM-like cells for the assessment of hTEM immunocompatibility. They adopt distinct pro- and anti-inflammatory phenotypes, and both IL-6 and IL-1ß secretion depends on hTEM composition. IL-6 provided the highest sensitivity to measure iMφs pro-inflammatory response. This platform could facilitate the in vitro immunocompatibility assessment of hTEMs and thereby showcase a potential way to achieve safer clinical translation of TEHVs.


Asunto(s)
Células Madre Pluripotentes Inducidas , Macrófagos , Ingeniería de Tejidos , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/inmunología , Ingeniería de Tejidos/métodos , Macrófagos/inmunología , Macrófagos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Células Cultivadas , Matriz Extracelular/metabolismo , Diferenciación Celular , Andamios del Tejido/química
6.
J Biomed Mater Res B Appl Biomater ; 112(6): e35411, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38773758

RESUMEN

The ultimate goal of tissue engineering is to repair and regenerate damaged tissue or organ. Achieving this goal requires blood vessel networks to supply oxygen and nutrients to new forming tissues. Macrophages are part of the immune system whose behavior plays a significant role in angiogenesis and blood vessel formation. On the other hand, macrophages are versatile cells that change their behavior in response to environmental stimuli. Given that implantation of a biomaterial is followed by inflammation; therefore, we reasoned that this inflammatory condition in tissue spaces modulates the final phenotype of macrophages. Also, we hypothesized that anti-inflammatory glucocorticoid dexamethasone improves modulating macrophages behavior. To check these concepts, we investigated the macrophages that had matured in an inflammatory media. Furthermore, we examined macrophages' behavior after maturation on a dexamethasone-containing scaffold and analyzed how the behavioral change of maturing macrophages stimulates other macrophages in the same environment. In this study, the expression of pro-inflammatory markers TNFa and NFκB1 along with pro-healing markers IL-10 and CD163 were investigated to study the behavior of macrophages. Our results showed that macrophages that were matured in the inflammatory media in vitro increase expression of IL-10, which in turn decreased the expression of pro-inflammatory markers TNFa and NFκB in maturing macrophages. Also, macrophages that were matured on dexamethasone-containing scaffolds decreased the expression of IL-10, TNFa, and NFκB and increase the expression of CD163 compared to the control group. Moreover, the modulation of anti-inflammatory response in maturing macrophages on dexamethasone-containing scaffold resulted in increased expression of TNFa and CD163 by other macrophages in the same media. The results obtained in this study, proposing strategies to improve healing through controlling the behavior of maturing macrophages and present a promising perspective for inflammation control using tissue engineering scaffolds.


Asunto(s)
Dexametasona , Interleucina-10 , Macrófagos , Poliésteres , Andamios del Tejido , Dexametasona/farmacología , Interleucina-10/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Andamios del Tejido/química , Poliésteres/química , Poliésteres/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Humanos , Animales , Inflamación/metabolismo , Ratones
7.
Food Res Int ; 187: 114425, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763673

RESUMEN

In this study, composite gel was prepared from konjac glucomannan (KGM) and fibrin (FN). Composite gels with different concentration ratios were compared in terms of their mechanical properties, rheological properties, water retention, degradation rate, microstructure and biocompatibility. The results showed that the composite gels had better gel strength and other properties than non-composite gels. In particular, composite hydrogels with low Young's modulus formed when the KGM concentration was 0.8% and the FN concentration was 1.2%. The two components were cross linked through hydrogen-bond interaction, which formed a more stable gel structure with excellent water retention and in-vitro degradation rates, which were conducive to myogenic differentiation of ectomesenchymal stem cells (EMSCs). KGM-FN composite gel was applied to the preparation of cell-culture meat, which had similar texture properties and main nutrients to animal meat as well as higher content of dry base protein and dry base carbohydrate.


Asunto(s)
Fibrina , Hidrogeles , Mananos , Reología , Mananos/química , Hidrogeles/química , Fibrina/química , Animales , Andamios del Tejido/química , Células Madre Mesenquimatosas , Carne , Diferenciación Celular , Módulo de Elasticidad , Técnicas de Cultivo de Célula
8.
Carbohydr Polym ; 338: 122204, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38763712

RESUMEN

This study presents the development and characterization of a novel double-network self-healing hydrogel based on N-carboxyethyl chitosan (CEC) and oxidized dextran (OD) with the incorporation of crosslinked collagen (CEC-OD/COL-GP) to enhance its biological and physicochemical properties. The hydrogel formed via dynamic imine bond formation exhibited efficient self-healing within 30 min, and a compressive modulus recovery of 92 % within 2 h. In addition to its self-healing ability, CEC-OD/COL-GP possesses unique physicochemical characteristics including transparency, injectability, and adhesiveness to various substrates and tissues. Cell encapsulation studies confirmed the biocompatibility and suitability of the hydrogel as a cell-culture scaffold, with the presence of a collagen network that enhances cell adhesion, spreading, long-term cell viability, and proliferation. Leveraging their unique properties, we engineered assemblies of self-healing hydrogel modules for controlled spatiotemporal drug delivery and constructed co-culture models that simulate angiogenesis in tumor microenvironments. Overall, the CEC-OD/COL-GP hydrogel is a versatile and promising material for biomedical applications, offering a bottom-up approach for constructing complex structures with self-healing capabilities, controlled drug release, and support for diverse cell types in 3D environments. This hydrogel platform has considerable potential for advancements in tissue engineering and therapeutic interventions.


Asunto(s)
Adhesión Celular , Quitosano , Dextranos , Hidrogeles , Hidrogeles/química , Hidrogeles/farmacología , Quitosano/química , Dextranos/química , Humanos , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colágeno/química , Animales , Liberación de Fármacos , Proliferación Celular/efectos de los fármacos , Encapsulación Celular/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones , Biomimética/métodos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Andamios del Tejido/química
9.
Mol Biol Rep ; 51(1): 675, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787484

RESUMEN

BACKGROUND: Bioscaffolds and cells are two main components in the regeneration of damaged tissues via cell therapy. Umbilical cord stem cells are among the most well-known cell types for this purpose. The main objective of the present study was to evaluate the effect of the pretreatment of the foreskin acellular matrix (FAM) by monophosphoryl lipid A (MPLA) and Lactobacillus casei supernatant (LCS) on the attraction of human umbilical cord mesenchymal stem cells (hucMSC). METHODS AND RESULTS: The expression of certain cell migration genes was studied using qRT-PCR. In addition to cell migration, transdifferentiation of these cells to the epidermal-like cells was evaluated via immunohistochemistry (IHC) and immunocytochemistry (ICC) of cytokeratin 19 (CK19). The hucMSC showed more tissue tropism in the presence of MPLA and LCS pretreated FAM compared to the untreated control group. We confirmed this result by scanning electron microscopy (SEM) analysis, glycosaminoglycan (GAG), collagen, and DNA content. Furthermore, IHC and ICC data demonstrated that both treatments increase the protein expression level of CK19. CONCLUSION: Pretreatment of acellular bioscaffolds by MPLA or LCS can increase the migration rate of cells and also transdifferentiation of hucMSC to epidermal-like cells without growth factors. This strategy suggests a new approach in regenerative medicine.


Asunto(s)
Lacticaseibacillus casei , Lípido A , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/metabolismo , Lacticaseibacillus casei/metabolismo , Lípido A/metabolismo , Lípido A/análogos & derivados , Movimiento Celular/efectos de los fármacos , Piel/metabolismo , Andamios del Tejido/química , Masculino , Cordón Umbilical/citología , Cordón Umbilical/metabolismo , Prepucio/citología , Transdiferenciación Celular/efectos de los fármacos , Ingeniería de Tejidos/métodos , Matriz Extracelular/metabolismo , Queratina-19/metabolismo , Queratina-19/genética
10.
Cell Transplant ; 33: 9636897241249556, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38742734

RESUMEN

Pancreatic islet transplantation is one of the clinical options for certain types of diabetes. However, difficulty in maintaining islets prior to transplantation limits the clinical expansion of islet transplantations. Our study introduces a dynamic culture platform developed specifically for primary human islets by mimicking the physiological microenvironment, including tissue fluidics and extracellular matrix support. We engineered the dynamic culture system by incorporating our distinctive microwell-patterned porous collagen scaffolds for loading isolated human islets, enabling vertical medium flow through the scaffolds. The dynamic culture system featured four 12 mm diameter islet culture chambers, each capable of accommodating 500 islet equivalents (IEQ) per chamber. This configuration calculates > five-fold higher seeding density than the conventional islet culture in flasks prior to the clinical transplantations (442 vs 86 IEQ/cm2). We tested our culture platform with three separate batches of human islets isolated from deceased donors for an extended period of 2 weeks, exceeding the limits of conventional culture methods for preserving islet quality. Static cultures served as controls. The computational simulation revealed that the dynamic culture reduced the islet volume exposed to the lethal hypoxia (< 10 mmHg) to ~1/3 of the static culture. Dynamic culture ameliorated the morphological islet degradation in long-term culture and maintained islet viability, with reduced expressions of hypoxia markers. Furthermore, dynamic culture maintained the islet metabolism and insulin-secreting function over static culture in a long-term culture. Collectively, the physiological microenvironment-mimetic culture platform supported the viability and quality of isolated human islets at high-seeding density. Such a platform has a high potential for broad applications in cell therapies and tissue engineering, including extended islet culture prior to clinical islet transplantations and extended culture of stem cell-derived islets for maturation.


Asunto(s)
Colágeno , Islotes Pancreáticos , Andamios del Tejido , Humanos , Islotes Pancreáticos/citología , Islotes Pancreáticos/metabolismo , Andamios del Tejido/química , Porosidad , Técnicas de Cultivo de Célula/métodos , Técnicas de Cultivo de Célula/instrumentación , Trasplante de Islotes Pancreáticos/métodos
11.
Biomed Mater ; 19(4)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38756029

RESUMEN

Hard tissue engineering scaffolds especially 3D printed scaffolds were considered an excellent strategy for craniomaxillofacial hard tissue regeneration, involving crania and facial bones and teeth. Porcine treated dentin matrix (pTDM) as xenogeneic extracellular matrix has the potential to promote the stem cell differentiation and mineralization as it contains plenty of bioactive factors similar with human-derived dentin tissue. However, its application might be impeded by the foreign body response induced by the damage-associated molecular patterns of pTDM, which would cause strong inflammation and hinder the regeneration. Ceria nanoparticles (CNPs) show a great promise at protecting tissue from oxidative stress and influence the macrophages polarization. Using 3D-bioprinting technology, we fabricated a xenogeneic hard tissue scaffold based on pTDM xenogeneic TDM-polycaprolactone (xTDM/PCL) and we modified the scaffolds by CNPs (xTDM/PCL/CNPs). Through series ofin vitroverification, we found xTDM/PCL/CNPs scaffolds held promise at up-regulating the expression of osteogenesis and odontogenesis related genes including collagen type 1, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein-2, osteoprotegerin, alkaline phosphatase (ALP) and DMP1 and inducing macrophages to polarize to M2 phenotype. Regeneration of bone tissues was further evaluated in rats by conducting the models of mandibular and skull bone defects. Thein vivoevaluation showed that xTDM/PCL/CNPs scaffolds could promote the bone tissue regeneration by up-regulating the expression of osteogenic genes involving ALP, RUNX2 and bone sialoprotein 2 and macrophage polarization into M2. Regeneration of teeth evaluated on beagles demonstrated that xTDM/PCL/CNPs scaffolds expedited the calcification inside the scaffolds and helped form periodontal ligament-like tissues surrounding the scaffolds.


Asunto(s)
Cerio , Matriz Extracelular , Nanopartículas , Osteogénesis , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido , Animales , Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Porcinos , Matriz Extracelular/metabolismo , Cerio/química , Nanopartículas/química , Ratas , Poliésteres/química , Dentina/química , Humanos , Regeneración Ósea/efectos de los fármacos , Odontogénesis , Diferenciación Celular , Regeneración , Macrófagos/metabolismo , Cráneo , Ratas Sprague-Dawley
12.
Nat Commun ; 15(1): 4160, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755128

RESUMEN

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.


Asunto(s)
Materiales Biocompatibles , Regeneración Ósea , Fibroínas , Magnesio , Células Madre Mesenquimatosas , Osteogénesis , Andamios del Tejido , Fibroínas/química , Fibroínas/farmacología , Regeneración Ósea/efectos de los fármacos , Animales , Andamios del Tejido/química , Masculino , Osteogénesis/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Ratas , Magnesio/química , Magnesio/farmacología , Materiales Biocompatibles/química , Osteoblastos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ratas Sprague-Dawley , Agua/química , Proliferación Celular/efectos de los fármacos , Ingeniería de Tejidos/métodos , Cráneo/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Bombyx
13.
Sci Adv ; 10(20): eadk6178, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38748794

RESUMEN

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.


Asunto(s)
Aloinjertos , Biomarcadores , Rechazo de Injerto , Animales , Rechazo de Injerto/inmunología , Ratones , Trasplante de Piel/efectos adversos , Trasplante de Corazón/efectos adversos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Tejido Subcutáneo/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Linfocitos T/inmunología , Linfocitos T/metabolismo
14.
J Nanobiotechnology ; 22(1): 250, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750519

RESUMEN

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.


Asunto(s)
Regeneración Ósea , Fosfatos de Calcio , Osteogénesis , Osteosarcoma , Andamios del Tejido , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Animales , Regeneración Ósea/efectos de los fármacos , Andamios del Tejido/química , Conejos , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Osteogénesis/efectos de los fármacos , Poliésteres/química , Humanos , Diferenciación Celular/efectos de los fármacos , Neoplasias Óseas/patología , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/terapia , Línea Celular Tumoral , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Células de Schwann/efectos de los fármacos , Nanofibras/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Selenio/química , Selenio/farmacología
15.
Cells ; 13(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38727297

RESUMEN

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Ratas Sprague-Dawley , Fusión Vertebral , Animales , Exosomas/metabolismo , Exosomas/trasplante , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Fusión Vertebral/métodos , Ratas , Osteogénesis/efectos de los fármacos , Fosfatos de Calcio/farmacología , Masculino , Humanos , Andamios del Tejido/química , Proteína Morfogenética Ósea 2/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos
16.
J Appl Biomater Funct Mater ; 22: 22808000241245298, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38733215

RESUMEN

In the current study, Cnicus benedictus extract was loaded into electrospun gelatin scaffolds for diabetic wound healing applications. Scaffolds were characterized in vitro by mechanical testing, cell culture assays, electron microscopy, cell migration assay, and antibacterial assay. In vivo wound healing study was performed in a rat model of diabetic wound. In vitro studies revealed fibrous architecture of our developed dressings and their anti-inflammatory properties. In addition, Cnicus benedictus extract-loaded wound dressings prevented bacterial penetration. In vivo study showed that wound size reduction, collagen deposition, and epithelial thickness were significantly greater in Cnicus benedictus extract-loaded scaffolds than other groups. Gene expression studies showed that the produced wound dressings significantly upregulated VEGF and IGF genes expression in diabetic wounds.


Asunto(s)
Vendajes , Diabetes Mellitus Experimental , Gelatina , Cicatrización de Heridas , Animales , Gelatina/química , Cicatrización de Heridas/efectos de los fármacos , Ratas , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/patología , Masculino , Humanos , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Antibacterianos/química , Antibacterianos/farmacología , Andamios del Tejido/química
18.
J Nanobiotechnology ; 22(1): 244, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735969

RESUMEN

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.


Asunto(s)
Macrófagos , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Poliuretanos , Ratas Sprague-Dawley , Células de Schwann , Animales , Regeneración Nerviosa/efectos de los fármacos , Poliuretanos/química , Ratas , Macrófagos/efectos de los fármacos , Células de Schwann/efectos de los fármacos , Nanofibras/química , Nervio Ciático/efectos de los fármacos , Regeneración Tisular Dirigida/métodos , Masculino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Andamios del Tejido/química , Ratones , Células RAW 264.7
19.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38731827

RESUMEN

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 µm as primary pores, 40-70 µm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.


Asunto(s)
Regeneración Ósea , Tibia , Andamios del Tejido , Animales , Perros , Andamios del Tejido/química , Tibia/diagnóstico por imagen , Proyectos Piloto , Osteogénesis , Porosidad , Microtomografía por Rayos X , Durapatita , Trasplante Óseo/métodos , Sustitutos de Huesos
20.
Biomed Mater ; 19(4)2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38729192

RESUMEN

In this study, we coated electrospun polycaprolactone (PCL) fibers with polydopamine (PDA) to modify their hydrophobicity and fabricated a matrix for culturing mesenchymal stem cells (MSCs). Additionally, we incorporated Arg-Gly-Asp (RGD) peptides into PDA to enhance MSCs culture performance on PCL fibers. PDA and RGD were successfully coated in one step by immersing the electrospun fibers in a coating solution, without requiring an additional surface activation process. The characteristics of functionalized PCL fibers were analyzed by scanning electron microscopy with energy-dispersive x-ray analysis, Fourier transform infrared spectroscopy, water contact angle measurement, and fluorescence measurements using a carboxylic-modified fluorescent microsphere. MSCs cultured on the modified PCL fibers demonstrated enhanced cell adhesion, proliferation, and osteogenic- and chondrogenic differentiation. This study provides insight into potential applications for scaffold fabrication in MSCs-based tissue engineering, wound dressing, implantation, and a deeper understanding of MSCs behaviorin vitro.


Asunto(s)
Adhesión Celular , Diferenciación Celular , Proliferación Celular , Indoles , Células Madre Mesenquimatosas , Osteogénesis , Poliésteres , Polímeros , Ingeniería de Tejidos , Andamios del Tejido , Células Madre Mesenquimatosas/citología , Humanos , Polímeros/química , Indoles/química , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Poliésteres/química , Osteogénesis/efectos de los fármacos , Células Cultivadas , Oligopéptidos/química , Oligopéptidos/farmacología , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , Condrogénesis/efectos de los fármacos , Técnicas de Cultivo de Célula , Interacciones Hidrofóbicas e Hidrofílicas
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