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Interface tissue repair requires the construction of biomaterials with integrated structures of multiple protein types. Hydrogels that modulate internal porous structures provide a 3D microenvironment for encapsulated cells, making them promise for interface tissue repair. Currently, reduction of intrinsic immunogenicity and increase of bioactive extracellular matrix (ECM) secretion are issues to be considered in these materials. In this study, gelatin methacrylate (GelMA) hydrogel is used to encapsulate chondrocytes and construct a phase transition 3D cell culture system (PTCC) by utilizing the thermosensitivity of gelatin microspheres to create micropores within the hydrogel. The types of bioactive extracellular matrix protein formation by chondrocytes encapsulated in hydrogels are investigated in vitro. After 28 days of culture, GelMA PTCC forms an extracellular matrix predominantly composed of collagen type II, collagen type I, and fibronectin. After decellularization, the protein types and mechanical properties are well preserved, fabricating a decellularized tissue-engineered extracellular matrix and GelMA hydrogel interpenetrating network hydrogel (dECM-GelMA IPN) consisting of GelMA hydrogel as the first-level network and the ECM secreted by chondrocytes as the second-level network. This material has the potential to mediate the repair and regeneration of tendon-bone interface tissues with multiple protein types.
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Gelatina , Hidrogéis , Hidrogéis/química , Gelatina/química , Materiais Biocompatíveis/química , Engenharia Tecidual , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Metacrilatos , Técnicas de Cultura de Células em Três Dimensões , Alicerces Teciduais/químicaRESUMO
BACKGROUND: Seroma formation is a common postsurgical complication of breast cancer surgery. It delays wound healing and may lead to other more serious complications. Conventional methods of reducing seroma formation through suturing or placement of surgical drainage produce inconsistent clinical outcomes. Tissue adhesives are viable alternatives but most of them are unsuitable for internal use and for large-area applications because of weak tissue adhesion strength or biocompatibility issues. The aim of this study was to evaluate the efficacy and biocompatibility of a mussel-inspired double-crosslinked tissue adhesive (DCTA) in reducing seroma formation after mastectomy. MATERIALS AND METHODS: Thirty-six female Sprague-Dawley rats were randomly assigned to either the saline control group (n = 12), the TISSEEL sealant (Baxter) group (n = 12), or the DCTA group (n = 12). After performing a mastectomy and applying the corresponding treatment, the efficacy of DCTA was evaluated by measurement of seroma volume while its biocompatibility was assessed via micronuclei test and histopathologic examination. RESULTS: During the 1-wk postsurgical period, the average total seroma volume of DCTA was significantly lower than the saline control group. Importantly, the mean seroma volume in DCTA showed a decreasing trend, whereas those in TISSEEL and saline control groups showed otherwise. The application of DCTA showed no genotoxic effect on the host and no severe inflammation. CONCLUSIONS: This study demonstrates that the good tissue adhesion strength and stability of DCTA were successful in reducing seroma formation over a period of 1 wk. Furthermore, the results also showed that it is biocompatible, which makes it suitable for large-area, internal use.
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Materiais Biocompatíveis/uso terapêutico , Adesivo Tecidual de Fibrina/uso terapêutico , Mastectomia , Complicações Pós-Operatórias/prevenção & controle , Seroma/prevenção & controle , Adesivos Teciduais/uso terapêutico , Animais , Bivalves , Feminino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Seroma/diagnóstico , Seroma/etiologia , Seroma/patologia , Resultado do TratamentoRESUMO
Glucosamine (GlcN) is a component of native cartilage extracellular matrix and useful in cartilage repair, but it was limited by toxicity in high concentrations. With the aim of altering bioactive properties of GlcN to reduce the toxicity and to facilitate chondrogenesis for hyaline cartilage formation, we introduced an amino-group modification with double bond into GlcN to produce N-acryloyl-glucosamine (AGA). The cell ATDC5 was chosen to evaluate its cytotoxicity and chondrogenesis capability. Cell proliferation and cytotoxicity assay showed that AGA had significantly reduced the cytotoxicity compared to GlcN, and promoted ATDC5 proliferation. Alcian blue staining and biochemical analysis indicated that AGA enhanced extracellular matrix deposition. Both the mRNA and protein levels of articular cartilage markers, like Collagen II and Aggrecan were up-regulated, as shown by quantitative real-time PCR and immunofluorescence staining. Moreover, the level of fibrocartilage marker Collagen I and hypertrophic marker Collagen Χ weren't significantly changed. Overall, these results demonstrated that the AGA achieved the functional double-bond, reduction in toxicity and enhancement in chondrogenesis could be more potential in cartilage repair.
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Diferenciação Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Glucosamina/química , Glucosamina/farmacologia , Alicerces Teciduais/química , Animais , Cartilagem Articular/citologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/fisiologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/fisiologia , Matriz Extracelular/química , Glucosamina/análogos & derivados , Teste de Materiais , CamundongosRESUMO
The stiffness of the extracellular matrix (ECM) is known to influence cell behavior. The ability to manipulate the stiffness of ECM has important implications in understanding how cells interact mechanically with their microenvironment. This article describes an approach to manipulating the stiffness ECM, whereby magnetic beads are embedded in the ECM through bioconjugation between the streptavidin-coated beads and the collagen fibers and then manipulated by an external magnetic field. It also reports both analytical results (obtained by formal modeling and numerical simulation) and statistically meaningful experimental results (obtained by atomic force microscopy) that demonstrate the effectiveness of this approach. These results clearly suggest the possibility of creating desired stiffness gradients in ECM in vitro to influence cell behavior.
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Módulo de Elasticidade , Matriz Extracelular/química , Campos Magnéticos , Animais , Colágeno/química , Microscopia de Força Atômica/instrumentação , Microscopia de Força Atômica/métodos , Microesferas , Modelos Biológicos , Ratos , Estreptavidina/químicaRESUMO
Osteoarthritis (OA) is primarily characterized by focal cartilage destruction and synovitis. Presently, the pathogenesis of OA remains unclear, and an effective treatment methodology is an unmet need. To this end, a plethora of animal models and monolayer models have been developed, but they are faced with the limitation of high cost and inability to recapitulate a pure hyaline cartilaginous phenotype, which is important in studying the efficacy of therapeutic agents. We have previously developed a living hyaline cartilage graft (LhCG) that accurately presented a pure hyaline cartilage phenotype. Here, through the coculture of lipopolysaccharide (LPS)-activated macrophages with LhCG, we hypothesized that an accurate OA disease model may be developed. Subsequently, this model was evaluated for its accuracy for in vitro drug testing. Results indicated that chondrocyte proliferation and apoptosis were increased in the disease model. Additionally, extracellular matrix (ECM) synthesis increased as indicated by the increased anabolic gene expression levels, such as collagen type II and aggrecan. Up-regulation of matrix metalloproteinase-1 (MMP-1) and MMP-3 genes suggested increased degradative activity, while chondrocytic hypertrophic differentiation was observed. Furthermore, extensive degradation of collagen type II and glycosaminoglycans (GAGs) were also observed. The results of celecoxib treatment on our model showed inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2) production, as well as down-regulation of MMP-1 and MMP-3 expression. Taken together, the results suggested that this coculture model was able to sufficiently mimic the native, diseased OA cartilage, while drug testing results confirmed its suitability as an in vitro model for predicting native cartilage response to drug treatment.
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Biomimética/métodos , Cartilagem Articular/efeitos dos fármacos , Celecoxib/farmacologia , Osteoartrite/tratamento farmacológico , Engenharia Tecidual/métodos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Condrócitos/efeitos dos fármacos , Colágeno Tipo II/genética , Dinoprostona/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Avaliação de Medicamentos/métodos , Matriz Extracelular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Glicosaminoglicanos/genética , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Camundongos , Óxido Nítrico/genética , Osteoartrite/genética , Transplantes , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
With the increasing research and deepening understanding of the glioblastoma (GBM) tumour microenvironment (TME), novel and more effective therapeutic strategies have been proposed. The GBM TME involves intricate interactions between tumour and non-tumour cells, promoting tumour progression. Key therapeutic goals for GBM treatment include improving the immunosuppressive microenvironment, enhancing the cytotoxicity of immune cells against tumours, and inhibiting tumour growth and proliferation. Consequently, remodeling the GBM TME using nanotechnology has emerged as a promising approach. Nanoparticle-based drug delivery enables targeted delivery, thereby improving treatment specificity, facilitating combination therapies, and optimizing drug metabolism. This review provides an overview of the GBM TME and discusses the methods of remodeling the GBM TME using nanotechnology. Specifically, it explores the application of nanotechnology in ameliorating immune cell immunosuppression, inducing immunogenic cell death, stimulating, and recruiting immune cells, regulating tumour metabolism, and modulating the crosstalk between tumours and other cells.
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Glioblastoma , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/imunologia , Glioblastoma/terapia , Glioblastoma/metabolismo , Humanos , Animais , Nanotecnologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Nanopartículas/química , Nanopartículas/administração & dosagem , Sistemas de Liberação de Medicamentos , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/químicaRESUMO
Complications can arise from damaging or removing lymph nodes after surgeries for malignant tumours. Our team has developed an innovative solution to recreate lymph nodes via an engineering approach. Using a Type II collagen scaffold coated with B cell membranes for the sake of attracting T cells in different regions, we could mimic the thymus-dependent and thymus-independent areas in vitro. This engineering strategy based on biophysical mimicry has a great potential for clinical applications. By further conjugating biological signals, anti-CD3/28, onto the scaffold coated with the B cell membrane, we achieved an 11.6-fold expansion of T cells within 14 days of in vitro culture while ensuring their activity, phenotype homeostasis, and differentiation capacity kept intact. Artificial lymph nodes had excellent biocompatibility and caused no pathological or physiological adverse effects after implantation into C57BL6 mice. In vivo assays also demonstrated that this artificial lymph node system positively adhered to omental tissues, creating an environment that fostered T cell growth and prevented cellular failure and death. Additionally, it induced vascular and lymphatic vessel invasion, which was beneficial to the migration and circulation of T cells between this system and peripheral blood. Due to the porous collagen fibre structure, it also facilitated the infiltration of host immune cells. This work opens new avenues to immune organ regeneration via a tissue engineering approach.
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Colágeno , Engenharia Tecidual , Animais , Camundongos , Porosidade , Camundongos Endogâmicos C57BL , Colágeno/química , Membrana Celular , Linfonodos/metabolismo , Alicerces Teciduais/químicaRESUMO
Cartilage injuries are escalating worldwide, particularly in aging society. Given its limited self-healing ability, the repair and regeneration of damaged articular cartilage remain formidable challenges. To address this issue, nanomaterials are leveraged to achieve desirable repair outcomes by enhancing mechanical properties, optimizing drug loading and bioavailability, enabling site-specific and targeted delivery, and orchestrating cell activities at the nanoscale. This review presents a comprehensive survey of recent research in nanomedicine for cartilage repair, with a primary focus on biomaterial design considerations and recent advances. The review commences with an introductory overview of the intricate cartilage microenvironment and further delves into key biomaterial design parameters crucial for treating cartilage damage, including microstructure, surface charge, and active targeting. The focal point of this review lies in recent advances in nano drug delivery systems and nanotechnology-enabled 3D matrices for cartilage repair. We discuss the compositions and properties of these nanomaterials and elucidate how these materials impact the regeneration of damaged cartilage. This review underscores the pivotal role of nanotechnology in improving the efficacy of biomaterials utilized for the treatment of cartilage damage.
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Materiais Biocompatíveis , Cartilagem Articular , Nanomedicina , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nanomedicina/métodos , Cartilagem Articular/efeitos dos fármacos , Animais , Sistemas de Liberação de Medicamentos , Engenharia Tecidual , Regeneração/efeitos dos fármacosRESUMO
Joint cartilage lesions affect the global population in the current aging society. Maintenance and rejuvenation of articular cartilage with hyaline phenotype remains a challenge as the underlying mechanism has not been completely understood. Here, we have designed and performed a mechanism study using scaffolds made of type II collagen (Col2) as the 3D cell cultural platforms, on some of which nanoaggregates comprising extracts of chondrocyte membrane (CCM) were coated as the antagonist of Col2. Dedifferentiated chondrocytes were, respectively, seeded into these Col2 based scaffolds with (antCol2S) or without (Col2S) CCM coating. After 6 weeks, in Col2S, the chondrocytes were rejuvenated to regain hyaline phenotype, whereas this redifferentiation effect was attenuated in antCol2S. Transcriptomic and proteomic profiling indicated that the Wnt/ß-catenin signaling pathway, which is an opponent to maintenance of the hyaline cartilaginous phenotype, was inhibited in Col2S, but it was contrarily upregulated in antCol2S due to the antagonism and shielding against Col2 by the CCM coating. Specifically, in antCol2S, since the coated CCM nanoaggregates contain the same components as those present on the surface of the seeded chondrocytes, the corresponding ligand sites on Col2 had been preoccupied and saturated by CCM coating before exposure to the seeded cells. The results indicated that the ligation between Col2 ligands and integrin α5 receptors on the surface of the seeded chondrocytes in antCol2S was antagonized by the CCM coating, which facilitates the Wnt/ß-catenin signaling toward the loss of hyaline cartilaginous phenotype. This finding reveals the contribution of Col2 for maintenance and rejuvenation of the hyaline cartilaginous phenotype in chondrocytes.
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Cartilagem Articular , Condrócitos , Condrócitos/metabolismo , Hialina/metabolismo , Proteômica , Células Cultivadas , Colágeno/metabolismo , FenótipoRESUMO
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by the disruption of the intestinal epithelial barrier. This study described the synthesis and characterization of CCM-Co-ZIF-8, a novel composite material with enzyme-like activities similar to catalase, peroxidase, and superoxide dismutase. CCM-Co-ZIF-8 demonstrated the ability to scavenge reactive oxygen species that play a critical role in UC pathogenesis. In vitro studies using lipopolysaccharide-induced RAW264.7 cells showed that CCM-Co-ZIF-8 exhibited anti-inflammatory activity by promoting the transition of macrophages from an M1 to an M2 phenotype. In vivo experiments using a mouse model of UC demonstrated that CCM-Co-ZIF-8 suppressed the expression of proinflammatory cytokines. These findings suggested that CCM-Co-ZIF-8 might hold promise as a therapeutic strategy for the treatment of UC.
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The bidirectional relationship between osteochondral defects (OCD) and osteoarthritis (OA), with each condition exacerbating the other, makes OCD regeneration in the presence of OA challenging. Type II collagen (Col2) is important in OCD regeneration and the management of OA, but its potential applications in cartilage tissue engineering are significantly limited. This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration. Furthermore, the repair potential of Col2 scaffolds was validated in over critical-sized OCD models. After 90 days or 150 days since scaffold implantation, complete healing was observed histologically in critical-sized OCD, evidenced by the excellent integration with surrounding native tissues. The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties. The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue. Additionally, transcriptome and proteome analysis revealed the hindrance of TGF-ß-Smad1/5/8 in regenerated OA tissue. In conclusion, the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-ß-Smad1/5/8 signaling pathway.
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The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.
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Hematopoietic stem cell (HSC) transplantation remains the most effective therapy for hematologic and lymphoid disorders. However, as the primary therapeutic cells, the source of HSCs has been limited due to the scarcity of matched donors and difficulties in ex vivo expansion. Here, we described a facile method to attempt the expansion of HSCs in vitro through a porous alginate hydrogel-based 3D culture system. We used gelatin powders as the porogen to create submillimeter-scaled pores in alginate gel bulk while pre-embedding naïve HSCs in the gel phase. The results indicated that this porous hydrogel system performed significantly better than those cultured via conventional suspension or encapsulation in non-porous alginate hydrogels in maintaining the phenotype and renewability of HSCs. Only the porous hydrogel system achieved a two-fold growth of CD34+ cells within seven days of culture, while the number of CD34+ cells in the suspension system and nonporous hydrogel showed different degrees of attenuation. The expansion efficiency of the porous hydrogel for CD34+CD38- cells was more than 2.2 times that of the other two systems. Mechanistic study via biophysical analysis revealed that the porous alginate system was competent to reduce the electron capture caused by biomaterials, decrease cellular oxygen stress, avoid oxidative protection, thus maintaining the cellular phenotype of the CD34+ cells. The transcriptomic analysis further suggested that the porous alginate system also upregulated the TNF signaling pathway and activated the NF-κB signaling pathway to promote the CD34+ cells' survival and maintain cellular homeostasis so that renewability was substantially favoured. STATEMENT OF SIGNIFICANCE: ⢠The reported porous hydrogel system performs significantly better in terms of maintaining the phenotype and renewability of HSCs than those cultured via conventional suspension or encapsulation in non-porous alginate hydrogel. ⢠The reported porous alginate system is competent to reduce the electron capture caused by biomaterials, decrease cellular oxygen stress, avoid oxidative protection, and therefore maintain the cellular phenotype of the CD34+ cells. ⢠The reported porous alginate system can also upregulate the TNF signaling pathway and activate the NF-κB signaling pathway to promote the CD34+ cells' survival and maintain cellular homeostasis so that the renewability is substantially favored..
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Células-Tronco Hematopoéticas , NF-kappa B , Células Cultivadas , NF-kappa B/metabolismo , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Materiais Biocompatíveis/metabolismo , Alginatos/farmacologia , Oxigênio/metabolismo , Antígenos CD34/metabolismo , Diferenciação Celular , Sangue FetalRESUMO
Traditional joint replacement surgery faces the risk of enormous trauma and secondary revision while using medication to relieve symptoms can cause bone thinning, weight gain and interference with the patient's pain signalling. Medical research has therefore focused on minimally invasive solutions for implanting tissue-engineered scaffolds to induce cartilage regeneration and repair. In cartilage tissue engineering, there are still technical barriers to seed cells, scaffold construction techniques, mechanical properties, and the regulation of the internal environment on the transplanted material. This issue focuses on the development of cartilage repair, cutting-edge discoveries, manufacturing technologies, and the current technological queries still faced in cartilage regenerative medicine research. The articles in this collection cover the coordination of physical and biochemical signals, genes, and regulations by the extracellular environment.
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Materiais Biocompatíveis , Cartilagem , Humanos , Materiais Biocompatíveis/química , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Medicina RegenerativaRESUMO
Articular cartilage defects significantly compromise the quality of life in the global population. Although many strategies are needed to repair articular cartilage, including microfracture, autologous osteochondral transplantation, and osteochondral allograft, the therapeutic effects remain suboptimal. In recent years, with the development of cartilage tissue engineering, scientists have continuously improved the formulations of therapeutic cells, biomaterial-based scaffolds, and biological factors, which have opened new avenues for better therapeutics of cartilage lesions. This review focuses on advances in cartilage tissue engineering, particularly in preclinical trials and clinical applications, prospects, and challenges.
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Catechins from green tea are one of the most effective natural compounds for cancer chemoprevention and have attracted extensive research. Cancer cell-selective apoptosis-inducing properties of catechins depend on efficient intracellular delivery. However, the low bioavailability limits the application of catechins. Herein, a nano-scaled micellar composite composed of catechin-functionalized cationic lipopolymer and serum albumin is constructed. Cationic liposomes tend to accumulate in the pulmonary microvasculature due to electrostatic effects and are able to deliver the micellar system intracellularly, thus improving the bioavailability of catechins. Albumin in the system acts as a biocompatible anti-plasma absorbent, forming complexes with positively charged lipopolymer under electrostatic interactions, contributing to prolonged in vivo retention. The physicochemical properties of the nano-micellar complexes are characterized, and the antitumor properties of catechin-functionalized materials are confirmed by reactive oxygen species (ROS), caspase-3, and cell apoptosis measurements. The role of each functional module, cationic polymeric liposome, and albumin is revealed by cell penetration, in vivo animal assays, etc. This multicomponent micellar nanocomposite has the potential to become an effective vehicle for the treatment of lung diseases such as pneumonia, lung tumors, sepsis-induced lung injury, etc. This study also demonstrates that it is a great strategy to create a delivery system that is both tissue-targeted and biologically active by combining cationic liposomes with the native bioactive compound catechins.
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Endochondral ossification (ECO) is a form of bone formation whereby the newly deposited bone replaces the cartilage template. A decellularized artificial cartilage graft (dLhCG), which is composed of hyaline cartilage matrixes, has been developed in our previous study. Herein, the osteogenesis of bone marrow-derived MSCs in the dLhCG through chondrogenic differentiation, chondrocyte hypertrophy, and subsequent transdifferentiation induction has been investigated by simulating the physiological processes of ECO for repairing critical-sized bone defects. The MSCs were recellularized into dLhCGs and subsequently allowed to undergo a 14-day proliferation period (mrLhCG). Following this, the mrLhCG constructs were subjected to two distinct differentiation induction protocols to achieve osteogenic differentiation: chondrogenic medium followed by chondrocytes culture medium with a high concentration of fetal bovine serum (CGCC group) and canonical osteogenesis inducing medium (OI group). The formation of a newly developed artificial bone graft, ossified dLhCG (OsLhCG), as well as its capability of aiding bone defect reconstruction were characterized by in vitro and in vivo trials, such as mRNA sequencing, quantitative real-time PCR (qPCR), immunohistochemistry, the greater omentum implantation in nude mice, and repair for the critical-sized femoral defects in rats. The results reveal that the differentiation induction of MSCs in the CGCC group can realize in vitro ECO through chondrogenic differentiation, hypertrophy, and transdifferentiation, while the MSCs in the OI group, as expected, realize ossification through direct osteogenic differentiation. The angiogenesis and osteogenesis of OsLhCG were proved by being implanted into the greater omentum of nude mice. Besides, the OsLhCG exhibits the capability to achieve the repair of critical-size femoral defects.
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Due to the safety issue and poor underwater adhesion of current commercially available bioadhesives, they are hard to apply to in vivo physiological environments and more diverse medical use conditions. In this study, a novel and facile bioadhesive for underwater medical applications are designed based on the coacervation of electrostatic interactions and hydrophobic interactions, with the introduction of catechin as a provider of catechol moieties for adhesion to surrounding tissues. The orange-colored bio-adhesive, named PcC, is generated within seconds by mixing catechin-modified chondroitin sulfate and cholesterol chloroformate-modified polyethyleneimine with agitation. In vitro mechanical measurements prove that this novel PcC bio-adhesive is superior in underwater adhesion performance when applied to cartilage. Animal experiments in a rat mastectomy model and rat cartilage graft implantation model demonstrate its potential for diverse medical purposes, such as closing surgical incisions, reducing the formation of seroma, and tissue adhesive applied in orthopedic or cartilage surgery.
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Catequina , Adesivos Teciduais , Ratos , Animais , Adesivos Teciduais/química , Sulfatos de Condroitina/farmacologia , Sulfatos de Condroitina/química , Polietilenoimina , Mastectomia , Adesivos/químicaRESUMO
Aging is inevitable, and how to age healthily is a key concern. Additive manufacturing offers many solutions to this problem. In this paper, we first briefly introduce various 3D printing technologies commonly used in the biomedical field, particularly in aging research and aging care. Next, we closely examine aging-related health conditions of nervous system, musculoskeletal system, cardiovascular system, and digestive system with a focus on the application of 3D printing in these fields, including the creation of in vitro models and implants, production of drugs and drug delivery systems, and fabrication of rehabilitation and assistive medical devices. Finally, the opportunities, challenges, and prospects of 3D printing in the field of aging are discussed.
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Tissue engineered cartilaginous constructs have meet great advances in the past decades as a treatment for osteoarthritis, a degenerative disease affecting people all over the world as the population ages. Scaffold-free tissue engineered constructs are designed and developed in recent years with only cells and cell-derived matrix involved. Scaffold-free tissue constructs do not require cell adherence on exogenous materials and are superior to scaffold-based constructs in (a) relying on only cells to produce matrix, (b) not interfering cell-cell signaling, cell migration or small molecules diffusion after implantation and (c) introducing no exogenous impurities. In this review, three main scaffold-free methodologies for cartilage tissue engineering, the cell sheet technology, the phase transfer cell culture-living hyaline cartilage graft system and the cell aggregate-based (bottom-up) methods, were reviewed, covering mold fabrication, decellularization and 3D bioprinting. The recent advances, medical applications, superiority and drawbacks were elaborated in detail.