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The ongoing global health has highlighted the critical issue of secondary infections, particularly antibiotic-resistant bacterial infections, which have been significant contributors to mortality rates. Orthopedic implants, while essential for trauma and orthopedic surgeries, are particularly susceptible to these infections, leading to severe complications and economic burdens. The traditional use of antibiotics in treating these infections poses further challenges including the risk of developing antibiotic-resistant bacteria. This study introduces a novel approach to combat this issue by developing nanostructured surfaces for orthopedic implants using target ion-induced plasma sputtering. Inspired by the natural design of dragonfly wings, these surfaces aim to prevent bacterial adhesion while promoting preosteoblast activity, offering a dual-function solution to the problems of bacterial infection and implant integration without relying on antibiotics. The in vitro results demonstrate the effectiveness of these bioinspired surfaces in eradicating bacteria and supporting cell proliferation and differentiation, presenting a promising alternative for the development of biomedical implants.
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Antibacterianos , Osseointegração , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Osseointegração/efeitos dos fármacos , Nanoestruturas/química , Camundongos , Propriedades de Superfície , Staphylococcus aureus/efeitos dos fármacos , Próteses e Implantes , Aderência Bacteriana/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem CelularRESUMO
Biliary strictures are characterized by the narrowing of the bile duct lumen, usually caused by surgical biliary injury, cancer, inflammation, and scarring from gallstones. Endoscopic stent placement is a well-established method for the management of biliary strictures. However, maintaining optimal mechanical properties of stents and designing surfaces that can prevent stent-induced tissue hyperplasia and biofilm formation are challenges in the fabrication of biodegradable biliary stents (BBSs) for customized treatment. This study proposes a novel approach to fabricating functionalized polymer BBSs with nanoengineered surfaces using 3D printing. The 3D printed stents, fabricated from bioactive silica poly(ε-carprolactone) (PCL) via a sol-gel method, exhibited tunable mechanical properties suitable for supporting the bile duct while ensuring biocompatibility. Furthermore, a nanoengineered surface layer was successfully created on a sirolimus (SRL)-coated functionalized PCL (fPCL) stent using Zn ion sputtering-based plasma immersion ion implantation (S-PIII) treatment to enhance the performance of the stent. The nanoengineered surface of the SRL-coated fPCL stent effectively reduced bacterial responses and remarkably inhibited fibroblast proliferation and initial burst release of SRL in vitro systems. The physicochemical properties and biological behaviors, including in vitro biocompatibility and in vivo therapeutic efficacy in the rabbit bile duct, of the Zn-SRL@fPCL stent demonstrated its potential as a versatile platform for clinical applications in bile duct tissue engineering.
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Chronic wounds in diabetic patients are challenging because their prolonged inflammation makes healing difficult, thus burdening patients, society, and health care systems. Customized dressing materials are needed to effectively treat such wounds that vary in shape and depth. The continuous development of 3D-printing technology along with artificial intelligence has increased the precision, versatility, and compatibility of various materials, thus providing the considerable potential to meet the abovementioned needs. Herein, functional 3D-printing inks comprising DNA from salmon sperm and DNA-induced biosilica inspired by marine sponges, are developed for the machine learning-based 3D-printing of wound dressings. The DNA and biomineralized silica are incorporated into hydrogel inks in a fast, facile manner. The 3D-printed wound dressing thus generates provided appropriate porosity, characterized by effective exudate and blood absorption at wound sites, and mechanical tunability indicated by good shape fidelity and printability during optimized 3D printing. Moreover, the DNA and biomineralized silica act as nanotherapeutics, enhancing the biological activity of the dressings in terms of reactive oxygen species scavenging, angiogenesis, and anti-inflammation activity, thereby accelerating acute and diabetic wound healing. These bioinspired 3D-printed hydrogels produce using a DNA-induced biomineralization strategy are an excellent functional platform for clinical applications in acute and chronic wound repair.
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Diabetes Mellitus , Hidrogéis , Masculino , Humanos , Hidrogéis/farmacologia , Inteligência Artificial , Biomineralização , Sêmen , Cicatrização , Impressão TridimensionalRESUMO
BACKGROUND: Diabetic wounds account for 25 to 50 percent of total diabetic health care costs annually, and present overall healing rates of less than 50 percent. Because delayed diabetic wound healing is associated with impaired fibroblast function, the authors hypothesize that tyrosine kinase Met (cMet) agonistic monoclonal antibody will promote diabetic wound healing by means of stable activation of hepatocyte growth factor/cMet signaling. METHODS: Two 6-mm dorsal wounds were created in each mouse (6-week-old, male BKS.Cg-Dock7 m +/+Lepr db /J; n = 5). After subcutaneous injections of agonist (20 mg/kg) at 0 and 72 hours, the wound sizes were measured at days 0, 1, 3, 6, and 10. Histologic and immunohistochemical analyses were performed at day 10 (cMet, α-smooth muscle actin, CD68, and transforming growth factor-ß). In vitro cytotoxicity and migration tests with diabetic fibroblasts were performed with or without agonist treatment (1 or 10 nM). cMet pathway activation of fibroblasts was confirmed through p-p44/42 mitogen-activated protein kinase, p-mTOR, p-cMet, and ROCK-1 expression. RESULTS: The cMet agonistic monoclonal antibody-treated group showed 1.60-fold lower wound area ( p = 0.027), 1.54-fold higher collagen synthesis ( p = 0.001), and 1.79-fold lower inflammatory cell infiltration ( p = 0.032) than the saline-treated control. The agonist increased cMet (1.86-fold; p = 0.029), α-smooth muscle actin (1.20-fold; p = 0.018), and vascular endothelial growth factor (1.68-fold, p = 0.029) expression but suppressed CD68 (1.25-fold; p = 0.043), transforming growth factor-ß (1.25-fold; p = 0.022), and matrix metalloproteinase-2 (2.59-fold; p = 0.029) expression. In vitro agonist treatment (10 nM) of diabetic fibroblasts increased their migration by 8.98-fold ( p = 0.029) and activated the hepatocyte growth factor/cMet pathway. CONCLUSIONS: Tyrosine kinase Met agonistic monoclonal antibody treatment improved diabetic wound healing in mice and reduced wound-site inflammatory cell infiltration. These results need to be validated in large animals before piloting human trials. CLINICAL RELEVANCE STATEMENT: Although further clinical studies are necessary to evaluate its therapeutic efficacy, our study suggested that cMet agonistic monoclonal antibody can be the alternative modality in order to improve wound healing cascade in diabetic foot patients.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Actinas , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Colágeno , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fator de Crescimento de Hepatócito , Humanos , Inflamação , Masculino , Metaloproteinase 2 da Matriz , Camundongos , Fatores de Crescimento Transformadores , Fator A de Crescimento do Endotélio VascularRESUMO
In recent years, pure iron (Fe) has attracted significant attention as a promising biodegradable orthopedic implant material due to its excellent mechanical and biological properties. However, in physiological conditions, Fe has an extremely slow degradation rate with localized and irregular degradation, which is problematic for practical applications. In this study, we developed a novel combination of a nanostructured surface topography and galvanic reaction to achieve uniform and accelerated degradation of an Fe implant. The target-ion induced plasma sputtering (TIPS) technique was applied on the Fe implant to introduce biologically compatible and electrochemically noble tantalum (Ta) onto its surface and develop surface nano-galvanic couples. Electrochemical tests revealed that the uniformly distributed nano-galvanic corrosion cells of the TIPS-treated sample (nano Ta-Fe) led to relatively uniform and accelerated surface degradation compared to that of bare Fe. Furthermore, the mechanical properties of nano Ta-Fe remained almost constant during a long-term in vitro immersion test (~40 weeks). Biocompatibility was also assessed on surfaces of bare Fe and nano Ta-Fe using in vitro osteoblast responses through direct and indirect contact assays and an in vivo rabbit femur medullary cavity implantation model. The results revealed that nano Ta-Fe not only enhanced cell adhesion and spreading on its surface, but also exhibited no signs of cellular or tissue toxicity. These results demonstrate the immense potential of Ta-implanted surface nanostructures as an effective solution for the practical application of Fe-based orthopedic implants, ensuring long-term biosafety and clinical efficacy.
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In recent years, freeform three-dimensional (3D) printing has led to significant advances in the fabrication of artificial tissues with vascularized structures. This technique utilizes a supporting matrix that holds the extruded printing ink and ensures shape maintenance of the printed 3D constructs within the prescribed spatial precision. Since the printing nozzle can be translated omnidirectionally within the supporting matrix, freeform 3D printing is potentially applicable for the fabrication of complex 3D objects, incorporating curved, and irregular shaped vascular networks. To optimize freeform 3D printing quality and performance, the rheological properties of the printing ink and supporting matrix, and the material matching between them are of paramount importance. In this review, we shall compare conventional 3D printing and freeform 3D printing technologies for the fabrication of vascular constructs, and critically discuss their working principles and their advantages and disadvantages. We also provide the detailed material information of emerging printing inks and supporting matrices in recent freeform 3D printing studies. The accompanying challenges are further discussed, aiming to guide freeform 3D printing by the effective design and selection of the most appropriate materials/processes for the development of full-scale functional vascularized artificial tissues.
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OBJECTIVE: Biodegradable poly-L-lactic acid (PLLA) with a highly biocompatible surface via tantalum (Ta) ion implantation can be an innovative solution for the problems associated with current biodegradable stents. The purpose of this study is to develop a Ta-implanted PLLA stent for clinical use and to investigate its biological performance capabilities. METHODS: A series of in vitro and in vivo tests were used to assess the biological performance of bare and Ta-implanted PLLA stents. The re-endothelialization ability and thrombogenicity were examined through in vitro endothelial cell and platelet adhesion tests. An in vivo swine model was used to evaluate the effects of Ta ion implantation on subacute restenosis and thrombosis. Angiographic and histologic evaluations were conducted at one, two and three months post-treatment. RESULTS: The Ta-implanted PLLA stent was successfully fabricated, exhibiting a smooth surface morphology and modified layer integration. After Ta ion implantation, the surface properties were more favorable for rapid endothelialization and for less platelet attachment compared to the bare PLLA stent. In an in vivo animal test, follow-up angiography showed no evidence of in-stent stenosis in either group. In a microscopic histologic examination, luminal thrombus formation was significantly suppressed in the Ta-implanted PLLA stent group according to the 2-month follow-up assessment (21.2% vs. 63.9%, p=0.005). Cells positive for CD 68, a marker for the monocyte lineage, were less frequently identified around the Ta-implanted PLLA stent in the 1-month follow-up assessments. CONCLUSION: The use of a Ta-implanted PLLA stent appears to promote re-endothelialization and anti-thrombogenicity.
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This single-blinded, randomized, controlled study aimed to clinically and radiographically evaluate hard tissue volume stability beyond the bony envelope using three-dimensional preformed titanium mesh (3D-PFTM) for peri-implant dehiscence defects in the anterior maxilla. A total of 28 patients who wished to undergo implant surgery combined with guided bone regeneration (GBR) after extraction of a single maxillary anterior tooth were randomly assigned to two groups depending on the type of collagen membrane used, additionally with the 3D-PFTM-test (n = 14, cross-linked collagen membrane; CCM) and control (n = 14, non-cross-linked collagen membrane; NCCM) groups. Each implant was evaluated radiographically using CBCT at baseline, immediately after surgery, and at 6 months postoperatively. The relative position and distances from the bony envelope to the outlines of the augmented ridge were further determined immediately after GBR and 6 months after healing. At the platform level, the mean horizontal hard tissue gain (HG) at all the sites was 2.35 ± 0.68 mm at 6 months postoperatively. The mean HG rate was 84.25% ± 14.19% in the CCM group and 82.56% ± 13.04% in the NCCM group, but the difference was not significant between the groups. In all cases, HG was maintained beyond the bony envelope even after 6 months of GBR. This study suggests that 3D-PFTM should be considered a valuable option for GBR for peri-implant dehiscence defects in the anterior maxilla. In addition, 3D-PFTM may confer predictable hard tissue volume stability even after the healing period of hard tissue augmented outside the bony envelope by GBR.
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Nano-scale surface roughening of metallic bio-implants plays an important role in the clinical success of hard tissue reconstruction and replacement. In this study, the nano-topographical features of titanium-niobium-zirconium (TNZ) alloy surfaces were controlled by using the target-ion induced plasma sputtering (TIPS) technique to improve the in vitro osteoblastic response. The TIPS technique is a novel strategy for etching the surface of metallic bio-implants using bombardment of target metal cations, which were accelerated by an extremely high negative bias voltage applied to the substrates. The nano-topography of the TNZ surfaces was successfully controlled by modulating experimental variables (such as the ion etching energy and the type of substrate or target materials) of TIPS. As a result, various nanopatterns (size: 10-210 nm) were fabricated on the surface of the TNZ alloys. Compared with the control group, experimental groups with nanopattern widths of ≥130 nm (130 and 210 nm groups) exhibited superior cell adhesion, proliferation, and differentiation. Our findings demonstrate that TIPS is a promising technology that can impart excellent biological functions to the surface of metallic bio-implants.
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Biodegradable magnesium (Mg)-based vascular stents can overcome the limitations of conventional permanent metallic stents, such as late in-stent restenosis and thrombosis, but still have difficulty retarding degradation while providing adequate mechanical support to the blood vessel. We incorporated silica nanoparticles surface-functionalized with hexadecyltrimethoxysilane (mSiNP) into a poly (l-lactic acid) (PLLA) coating as a physical barrier to disturb the penetration of the corrosive medium as well as a bioactive source that releases silicon ions capable of stimulating endothelial cells. The corrosion resistance and biocompatibility of this bifunctional PLLA/mSiNP nanocomposite coating were investigated using different weight ratios of mSiNP. The nanocomposite coating containing more than 10 wt% of the mSiNP (PLLA/10mSiNP and PLLA/20mSiNP) significantly delayed the corrosion of the Mg substrate and exhibited favorable endothelial cell responses, compared to the pure PLLA coating. Specifically, the calculated corrosion rates of PLLA/10mSiNP and PLLA/20mSiNP decreased by half, indicating the durability of the coating after immersion in simulated body fluid for 12 days. Based on the in vitro cellular response, the incorporation of the mSiNPs into the PLLA coating significantly improved the endothelial cell responses to the Mg substrate, showing better initial cell surface coverage, migration, and proliferation rate than those of pure PLLA. These results indicate that the PLLA/mSiNP nanocomposite coatings have significant potential to improve the corrosion resistance and vascular compatibility of biodegradable Mg-based vascular stents.
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Magnésio , Nanocompostos , Materiais Revestidos Biocompatíveis/farmacologia , Corrosão , Células Endoteliais , Ácido Láctico , Teste de Materiais , Poliésteres , Dióxido de Silício , StentsRESUMO
Poly(ether imide) (PEI) has shown satisfactory corrosion protection capability with good adhesion strength as a coating for magnesium (Mg), a potential candidate of biodegradable orthopedic implant material. However, its innate hydrophobic property causes insufficient osteoblast affinity and a lack of osseointegration. Herein, we modify the physical and chemical properties of a PEI-coated Mg implant. A plasma immersion ion implantation technique is combined with direct current (DC) magnetron sputtering to introduce biologically compatible tantalum (Ta) onto the surface of the PEI coating. The PEI-coating layer is not damaged during this process owing to the extremely short processing time (30 s), retaining its high corrosion protection property and adhesion stability. The Ta-implanted layer (roughly 10-nm-thick) on the topmost PEI surface generates long-term surface hydrophilicity and favorable surface conditions for pre-osteoblasts to adhere, proliferate, and differentiate. Furthermore, in a rabbit femur study, the Ta/PEI-coated Mg implant demonstrates significantly enhanced bone tissue affinity and osseointegration capability. These results indicate that Ta/PEI-coated Mg is promising for achieving early mechanical fixation and long-term success in biodegradable orthopedic implant applications.
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Powder based additive manufacturing (AM) technology of Ti and its alloys has received great attention in biomedical applications owing to its advantages such as customized fabrication, potential to be cost-, time-, and resource-saving. The performance of additive manufactured implants or scaffolds strongly depends on various kinds of AM technique and the quality of Ti and its alloy powders. This paper has specifically covered the process of commonly used powder-based AM technique and the powder production of Ti and its alloy. The selected techniques include laser-based powder bed fusion of metals (PBF-LB/M), electron beam powder bed fusion of metals (PBF-EB/M), and directed energy deposition utilized in the production of the biomaterials are discussed as well as the powder fed system of binder jetting. Moreover, titanium based powder production methods such as gas atomization, plasma atomization, and plasma rotating electrode process are also discussed.
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Poly(L-lactic) acid (PLLA) is among the most promising polymers for bone fixation, repair, and tissue engineering due to its biodegradability and relatively good mechanical strength. Despite these beneficial characteristics, its poor bioactivity often requires incorporation of bioactive ceramic materials. A bioresorbable composite made of PLLA and hydroxyapatite (HA) may improve biocompatibility but typically causes deterioration in mechanical properties, and bioactive coatings inevitably carry a risk of coating delamination. Therefore, in this study, we embedded micropatterned HA on the surface of PLLA to improve bioactivity while eliminating the risk of HA delamination. An HA pattern was successfully embedded in a PLLA matrix without degeneration of the matrix's mechanical properties, thanks to a transfer technique involving conversion of Mg to HA. Furthermore, patterned HA/PLLA's biological response outperformed that of pure PLLA. These results confirm patterned HA/PLLA as a candidate for wide acceptance in biodegradable load-bearing implant applications.
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Composite hydrogels have gained great attention as three-dimensional (3D) printing biomaterials because of their enhanced intrinsic mechanical strength and bioactivity compared to pure hydrogels. In most conventional printing methods for composite hydrogels, particles are preloaded in ink before printing, which often reduces the printability of composite ink with little mechanical improvement due to poor particle-hydrogel interaction of physical mixing. In contrast, the in situ incorporation of nanoparticles into a hydrogel during 3D printing achieves uniform distribution of particles with remarkable mechanical reinforcement, while precursors dissolved in inks do not influence the printing process. Herein, we introduced a "printing in liquid" technique coupled with a hybridization process, which allows 3D freeform printing of nanoparticle-reinforced composite hydrogels. A viscoplastic matrix for this printing system provides not only support for printed hydrogel filaments but also chemical reactants to induce various reactions in printed objects for in situ modification. Nanocomposite hydrogel scaffolds were successfully fabricated through this 3D freeform printing of hyaluronic acid (HAc)-alginate (Alg) hydrogel inks through a two-step crosslinking strategy. The first ionic crosslinking of Alg provided structural stability during printing, while the secondary crosslinking of photo-curable HAc improved the mechanical and physiological stability of the nanocomposite hydrogels. For in situ precipitation during 3D printing, phosphate ions were dissolved in the hydrogel ink and calcium ions were added to the viscoplastic matrix. The composite hydrogels demonstrated a significant improvement in mechanical strength, biostability, as well as biological performance compared to pure HAc. Moreover, the multi-material printing of composites with different calcium phosphate contents was achieved by adjusting the ionic concentration of inks. Our method greatly accelerates the 3D printing of various functional or hybridized materials with complex geometries through the design and modification of printing materials coupled with in situ post-printing functionalization and hybridization in reactive viscoplastic matrices.
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Biofabrication with various hydrogel systems allows the production of tissue or organ constructs in vitro to address various challenges in healthcare and medicine. In particular, photocrosslinkable hydrogels have great advantages such as excellent spatial and temporal selectivity and low processing cost and energy requirements. However, inefficient polymerization kinetics of commercialized photoinitiators upon exposure to UV-A radiation or visible light increase processing time, often compromising cell viability. In this study, we developed a hydrogel crosslinking system which exhibited efficient crosslinking properties and desired mechanical properties with high cell viability, through a dual-photoinitiator approach. Through the co-existence of Irgacure 2959 and VA-086, the overall crosslinking process was completed with a minimal UV dosage during a significantly reduced crosslinking time, producing mechanically robust hydrogel constructs, while most encapsulated cells within the hydrogel constructs remained viable. Moreover, we fabricated a large PEGDA hydrogel construct with a single microchannel as a proof of concept for hydrogels with vasculature to demonstrate the versatility of the system. Our dual-photoinitiator approach allowed the production of this photocrosslinkable hydrogel system with microchannels, significantly improving cell viability and processing efficiency, yet maintaining good mechanical stability. Taken together, we envision the concurrent use of photoinitiators, Irgacure 2959 and VA-086, opening potential avenues for the utilization of various photocrosslinkable hydrogel systems in perfusable large artificial tissue for in vivo and ex vivo applications with improved processing efficiency and cell viability.
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Acetamidas/farmacologia , Compostos Azo/farmacologia , Fibroblastos/citologia , Propano/análogos & derivados , Acetamidas/química , Animais , Compostos Azo/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas , Fibroblastos/efeitos dos fármacos , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Luz , Camundongos , Impressão Tridimensional , Propano/química , Propano/farmacologia , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Bare metal stents are commonly used in interventional cardiology; they provide successful treatment because of their excellent mechanical properties, expandability ratios, and flexibility. However, their insufficient vascular affinity can induce the development of neointimal hyperplasia following arterial injury and subsequent smooth muscle cell overgrowth in the lumen of a stented vessel. Nanoengineering of the bare metal stent surface is a valuable strategy for eliciting favorable vascular responses. In this study, we introduce a target-ion-induced plasma sputtering (TIPS) technique to fabricate a platform with a favorable endothelial environment. This technique enables the simple single-step production of a Ta-implanted nanoridged surface on a stent with a complex 3D geometry that shows a clear tendency to become oriented parallel to the direction of blood flow. Moreover, the nanoridges developed show good structural integrity and mechanical stability, resulting in apparently stable morphologies under high strain rates. In vitro cellular responses to the Co-Cr, such as endothelialization, platelet activation, and blood coagulation, are considerably altered after TIPS treatment; endothelium formation is rapid and surface thrombogenicity is low. An in vivo rabbit iliac artery model is used to confirm that the nanoridged surface facilitates rapid re-endothelialization and limits the formation of neointima compared to the bare stent. These results indicate that the Ta ion implanted nanoridge platform fabricated using the TIPS technique has immense potential as a solution for in-stent restenosis and ensuring the long-term patency of bare metal stents.
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Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Nanopartículas/química , Stents , Tantálio/química , Animais , Coagulação Sanguínea , Adesão Celular , Movimento Celular , Proliferação de Células , Materiais Revestidos Biocompatíveis , Endotélio Vascular/patologia , Análise de Fourier , Humanos , Hiperplasia , Íons , Masculino , Metais/química , Miócitos de Músculo Liso , Nanotecnologia , Neointima/patologia , Ativação Plaquetária , Coelhos , Estresse MecânicoRESUMO
Polyetheretherketone (PEEK), one of the potential alternatives to metallic materials for implants, necessarily involves high temperature process conditions to be three-dimensionally (3D) printed. We developed a 3D printing setup equipped with thermally stabilized modules of the printing nozzle and building chamber, by which the PEEK implants could be successfully manufactured. Under optimized printing conditions, the maximal mechanical strength of the 3D printed sample attained over 80% of the original bulk property of PEEK. To enhance the interfacial biocompatibility, the as-printed implants were postprocessed with titanium (Ti) sputtering. The Ti-coated surfaces were evaluated through characterization studies of x-ray diffraction spectra, microscopic topographies, and wetting properties. For the in vitro tests, preosteoblasts were cultured on the developed PEEK-Ti structures and evaluated in terms of cell adhesion, proliferation, and osteogenic differentiation. In addition, the bone regeneration capability of the PEEK-Ti implants was confirmed by animal experiments using a rabbit tibia defect model for a period of 12 weeks. In the overall in vitro and in vivo tests, we confirmed the superior bioactivities of the Ti-modified and 3D printed interface by comparisons between the samples of machined and printed samples with or without Ti coating. Taken together, the comprehensive manufacturing approaches that involve 3D printing and biocompatible postprocessing are expected to have universal applicability in a wide range of bone tissue engineering.
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Materiais Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Temperatura Alta , Cetonas/farmacologia , Polietilenoglicóis/farmacologia , Impressão Tridimensional , Próteses e Implantes , Titânio/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Benzofenonas , Regeneração Óssea/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Imageamento Tridimensional , Masculino , Camundongos , Imagem Óptica , Polímeros , Coelhos , Propriedades de Superfície , Resistência à Tração , Difração de Raios X , Microtomografia por Raio-XRESUMO
Although the design of more biocompatible polymeric implants has been studied for decades, their intended functionality continues to be impaired by the response of the host tissue to foreign bodies at the tissue-implant interface. In particular, the formation and contracture of fibrous capsules prevent the intimate integration of an implant with surrounding tissues, which leads to structural deformation of the implants and persistent discomfort and pain. We report a new surface nano-engineered silicone implant that reduces fibrous capsule formation and improves the biocompatibility of it via sputtering-based plasma immersion ion implantation (S-PIII). This technique can introduce biologically compatible tantalum (Ta) on the silicone surface to produce a Ta-implanted skin layer (<60 nm thick) as well as generate either smooth (Smooth/Ta silicone) or nano-textured (Nano/Ta silicone) surface morphologies. The biologically inert chemical structure and strong hydrophobic surface characteristics of bare silicone are substantially ameliorated after Ta ion implantation. In particular, the Nano/Ta silicone implant's combination of surface nano-texturing as a physical cue and the Ta-implanted layer as a chemical cue was found to be very effective at achieving outstanding hydrophilicity and fibroblast affinity compared to the bare and Smooth/Ta silicone implants. In a mouse in vivo study conducted for 8 weeks, the Nano/Ta silicone implant inhibited fibrous capsule formation and contracture on its surface better than the bare silicone based on an analysis of the number of macrophages, myofibroblast differentiation and activation, collagen density, and thickness of fibrous capsules.
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Engenharia , Nanotecnologia , Próteses e Implantes , Silicones/química , Tantálio/química , Animais , Fibroblastos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Fenômenos Mecânicos , Ativação Plaquetária/efeitos dos fármacos , Adesividade Plaquetária/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Silicones/farmacologia , Propriedades de SuperfícieRESUMO
The surface characteristics of coronary stents play a pivotal role in inhibiting in-stent restenosis and late-stent thrombosis. In this study, a sol-gel-derived silica xerogel-chitosan hybrid coating was applied to Co-Cr stent and was reported, for the first time, as a biocompatible drug delivery tool in vascular stent application. A dense and uniform chitosan-silica xerogel hybrid coating (<1-µm thick) was applied on bare Co-Cr material. Sirolimus was well incorporated into the hybrid coatings without re-crystallization. The chitosan-silica hybrid coating with 30 wt% silica xerogel showed better mechanical stability and good adhesive strength without any cracking or delamination. The chitosan-silica hybrid coated Co-Cr surface exhibited significantly improved wettability and corrosion resistance compared to the chitosan coated Co-Cr surface. In addition, the hybrid coating layer enabled efficient loading of sirolimus, owing to the unique mesoporous structure of silica xerogel, which further allowed the sustained release of sirolimus over 3 weeks. In-vitro tests with human umbilical cord vein endothelial cells and blood platelets confirmed that the chitosan-silica hybrid coating had excellent cytocompatibility and hemocompatibilty. Thus, this study demonstrated that the chitosan-silica hybrid material is a promising material for coating coronary stents, with minimal risk of in-stent restenosis and thrombogenicity.
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Materiais Revestidos Biocompatíveis/química , Stents Farmacológicos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Compostos Inorgânicos/química , Teste de Materiais , Compostos Orgânicos/química , Sirolimo/farmacologia , Quitosana/química , Humanos , Adesividade Plaquetária/efeitos dos fármacos , Dióxido de Silício/química , MolhabilidadeRESUMO
Biofabrication technologies have endowed us with the capability to fabricate complex biological constructs. However, cytotoxic biofabrication conditions have been a major challenge for their clinical application, leading to a trade-off between cell viability and scalability of biofabricated constructs. Taking inspiration from nature, we proposed a cell protection strategy which mimicks the protected and dormant state of plant seeds in adverse external conditions and their germination in response to appropriate environmental cues. Applying this bioinspired strategy to biofabrication, we successfully preserved cell viability and enhanced the seeding of cell-laden biofabricated constructs via a cytoprotective pyrogallol (PG)-alginate encapsulation system. Our cytoprotective encapsulation technology utilizes PG-triggered sporulation and germination processes to preserve cells, is mechanically robust, chemically resistant, and highly customizable to adequately match cell protectability with cytotoxicity of biofabrication conditions. More importantly, the facile and tunable decapsulation of our PG-alginate system allows for effective germination of dormant cells, under typical culture conditions. With this approach, we have successfully achieved a biofabrication process which is reproducible, scalable, and provided a practical solution for off-the-shelf availability, shipping and temporary storage of fabricated bio-constructs.