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Surface bio-engineering of polymeric nanoparticles (PNPs) has emerged as a cornerstone in contemporary biomedical research, presenting a transformative avenue that can revolutionize diagnostics, therapies, and drug delivery systems. The approach involves integrating bioactive elements on the surfaces of PNPs, aiming to provide them with functionalities to enable precise, targeted, and favorable interactions with biological components within cellular environments. However, the full potential of surface bio-engineered PNPs in biomedicine is hampered by obstacles, including precise control over surface modifications, stability in biological environments, and lasting targeted interactions with cells or tissues. Concerns like scalability, reproducibility, and long-term safety also impede translation to clinical practice. In this review, these challenges in the context of recent breakthroughs in developing surface-biofunctionalized PNPs for various applications, from biosensing and bioimaging to targeted delivery of therapeutics are discussed. Particular attention is given to bonding mechanisms that underlie the attachment of bioactive moieties to PNP surfaces. The stability and efficacy of surface-bioengineered PNPs are critically reviewed in disease detection, diagnostics, and treatment, both in vitro and in vivo settings. Insights into existing challenges and limitations impeding progress are provided, and a forward-looking discussion on the field's future is presented. The paper concludes with recommendations to accelerate the clinical translation of surface bio-engineered PNPs.
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Nanopartículas , Polímeros , Nanopartículas/química , Polímeros/química , Humanos , Animais , Propriedades de Superfície , Sistemas de Liberação de Medicamentos/métodosRESUMO
TiCu coatings with controlled copper release and nano-porous structures were fabricated as biocompatible, blood-contacting interfaces through a two-step process. Initially, coatings with 58 % Cu were created using HiPIMS/DC magnetron co-sputtering, followed by immersion in a dilute HF solution for varying durations to achieve dealloying. The presence of Ti elements in the as-deposited TiCu coatings facilitated their dissolution upon exposure to the dilute HF solution, resulting in the formation of nanopores and increased nano-roughness. Dealloying treatment time correlated with higher Cu/(Ti + Cu) values, nanopore size, and nano-roughness in the dealloyed samples. The dealloyed TiCu coatings with 87 % Cu exhibited a controlled release of copper ions and displayed nanopores (approximately 80 nm in length and 31.0 nm in width) and nano-roughness (Ra roughness: 82 nm). These coatings demonstrated inhibited platelet adhesion and suppressed smooth muscle cell behavior, while supporting favorable endothelial cell viability and proliferation, attributed to the controlled release of copper ions and the extent of nanostructures. In contrast, the as-deposited TiCu coatings with 85 % Cu showed high copper ion release, leading to decreased viability and proliferation of endothelial cells and smooth muscle cells, as well as suppressed platelet adhesion. The TiCu coatings met medical safety standards, exhibiting hemolysis rates of <5 %. The technology presented here paves the way for the simple, controllable, and cost-effective fabrication of TiCu coatings, opening new possibilities for surface modification of cardiovascular devices such as vascular stents and inferior vena cava filters.
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Sistema Cardiovascular , Cobre , Cobre/farmacologia , Células Endoteliais , Preparações de Ação Retardada , ÍonsRESUMO
Mesenchymal stem cells (MSCs) used for clinical applications require in vitro expansion to achieve therapeutically relevant numbers. However, conventional planar cell expansion approaches using tissue culture vessels are inefficient, costly, and can trigger MSC phenotypic and functional decline. Here we present a one-step dry plasma process to modify the internal surfaces of three-dimensional (3D) printed, high surface area to volume ratio (high-SA:V) porous scaffolds as platforms for stem cell expansion. To address the long-lasting challenge of uniform plasma treatment within the micrometre-sized pores of scaffolds, we developed a packed bed plasma immersion ion implantation (PBPI3) technology by which plasma is ignited inside porous materials for homogeneous surface activation. COMSOL Multiphysics simulations support our experimental data and provide insights into the role of electrical field and pressure distribution in plasma ignition. Spatial surface characterisation inside scaffolds demonstrates the homogeneity of PBPI3 activation. The PBPI3 treatment induces radical-containing chemical structures that enable the covalent attachment of biomolecules via a simple, non-toxic, single-step incubation process. We showed that PBPI3-treated scaffolds biofunctionalised with fibroblast growth factor 2 (FGF2) significantly promoted the expansion of MSCs, preserved cell phenotypic expression, and multipotency, while reducing the usage of costly growth factor supplements. This breakthrough PBPI3 technology can be applied to a wide range of 3D polymeric porous scaffolds, paving the way towards developing new biomimetic interfaces for tissue engineering and regenerative medicine.
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Hydrogel-based drug delivery systems (DDSs) can leverage therapeutically beneficial outcomes in cancer therapy. In this domain, polyethylene glycol (PEG) has become increasingly popular as a biomedical polymer and has found clinical use. Owing to their excellent biocompatibility, facile modifiability, and high drug encapsulation rate, PEG hydrogels have shown great promise as drug delivery platforms. Here, the progress in emerging novel designs of PEG-hydrogels as DDSs for anti-cancer therapy is reviewed and discussed, focusing on underpinning multiscale release mechanisms categorized under stimuli-responsive and non-responsive drug release. The responsive drug delivery approaches are discussed, and the underpinning release mechanisms are elucidated, covering the systems functioning based on either exogenous stimuli-response, such as photo- and magnetic-sensitive PEG hydrogels, or endogenous stimuli-response, such as enzyme-, pH-, reduction-, and temperature-sensitive PEG hydrogels. Special attention is paid to the commercial potential of PEG-based hydrogels in cancer therapy, highlighting the limitations that need to be addressed in future research for their clinical translation.
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Sistemas de Liberação de Medicamentos , Hidrogéis , Neoplasias , Polietilenoglicóis , Materiais Biocompatíveis , Neoplasias/tratamento farmacológico , Polímeros , HumanosRESUMO
Strategies to promote rapid formation of functional endothelium are required to maintain blood fluidity and regulate smooth muscle cell proliferation in synthetic vascular conduits. In this work, we explored the biofunctionalization of silk biomaterials with recombinantly expressed domain V of human perlecan (rDV) to promote endothelial cell interactions and the formation of functional endothelium. Perlecan is essential in vascular development and homeostasis and rDV has been shown to uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions, both key contributors of vascular graft failure. rDV was covalently immobilized on silk using plasma immersion ion implantation (PIII), a simple one-step surface treatment process which enables strong immobilization in the absence of chemical cross-linkers. rDV immobilization on surface-modified silk was assessed for amount, orientation, and bio-functionality in terms of endothelial cell interactions and functional endothelial layer formation. rDV immobilized on PIII-treated silk (rDV-PIII-silk) supported rapid endothelial cell adhesion, spreading, and proliferation to form functional endothelium, as evidenced by the expression of vinculin and VE-cadherin markers. Taken together, the results provide evidence for the potential of rDV-PIII-silk as a biomimetic vascular graft material.
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Materiais Biocompatíveis , Seda , Humanos , Seda/química , Imersão , Adesão Celular , Prótese Vascular , Proteínas da Matriz Extracelular , EndotélioRESUMO
AlCrFeCoNiCu0.5 thin films were fabricated by cathodic arc deposition under different substrate biases. Detailed characterization of the chemistry and structure of the film, from the substrate interface to the film surface, was achieved by combining high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. Computer simulations using the transport of ions in matter model were applied to understand the ion surface interactions that revealed the key mechanism of the film growth. The final compositions of the films are significantly different from that of the target used. A trend of elemental segregation, which was more pronounced with higher ion kinetic energy, was observed. The XPS results reveal the formation of [Formula: see text] and [Formula: see text] on the thin film surface. The grain size is shown to increase with the increasing of the ion kinetic energy. The growth of equiaxed grains contributed to the formation of a flat surface with a relatively low surface roughness as shown by atomic force microscopy.
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Mesenchymal stromal/stem cells (MSCs) typically require significant ex vivo expansion to achieve the high cell numbers required for research and clinical applications. However, conventional MSC culture on planar (2D) plastic surfaces has been shown to induce MSC senescence and decrease cell functionality over long-term proliferation, and usually, it has a high labor requirement, a high usage of reagents, and therefore, a high cost. In this Review, we describe current MSC-based therapeutic strategies and outline the important factors that need to be considered when developing next-generation cell expansion platforms. To retain the functional value of expanded MSCs, ex vivo culture systems should ideally recapitulate the components of the native stem cell microenvironment, which include soluble cues, resident cells, and the extracellular matrix substrate. We review the interplay between these stem cell niche components and their biological roles in governing MSC phenotype and functionality. We discuss current biomimetic strategies of incorporating biochemical and biophysical cues in MSC culture platforms to grow clinically relevant cell numbers while preserving cell potency and stemness. This Review summarizes the current state of MSC expansion technologies and the challenges that still need to be overcome for MSC clinical applications to be feasible and sustainable.
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Biomimética , Células-Tronco Mesenquimais , Matriz Extracelular/metabolismo , Fenótipo , Células-Tronco Mesenquimais/metabolismoRESUMO
Titanium (Ti) has been widely used for manufacturing of bone implants because of its mechanical properties, biological compatibility, and favorable corrosion resistance in biological environments. However, Ti implants are prone to infection (peri-implantitis) by bacteria which in extreme cases necessitate painful and costly revision surgeries. An emerging, viable solution for this problem is to use copper (Cu) as an antibacterial agent in the alloying system of Ti. The addition of copper provides excellent antibacterial activities, but the underpinning mechanisms are still obscure. This review sheds light on such mechanisms and reviews how incorporation of Cu can render Ti-Cu implants with antibacterial activity. The review first discusses the fundamentals of interactions between bacteria and implanted surfaces followed by an overview of the most common engineering strategies utilized to endow an implant with antibacterial activity. The underlying mechanisms for antibacterial activity of Ti-Cu implants are then discussed in detail. Special attention is paid to contact killing mechanisms because the misinterpretation of this mechanism is the root of discrepancies in the literature.
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Blood compatible materials are required for the development of therapeutic and diagnostic blood contacting devices as blood-material interactions are a key factor dictating device functionality. In this work, we explored biofunctionalization of silk biomaterials with a recombinantly expressed domain V of the human basement membrane proteoglycan perlecan (rDV) towards the development of blood compatible surfaces. Perlecan and rDV are of interest in vascular device development as they uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions. rDV was covalently immobilized on silk biomaterials using plasma immersion ion implantation (PIII), a new method of immobilizing proteins on silk biomaterials that does not rely on modification of specific amino acids in the silk protein chain, and compared to physisorbed and carbodiimide immobilized rDV. Untreated and treated silk biomaterials were examined for interactions with blood components with varying degrees of complexity, including isolated platelets, platelet rich plasma, blood plasma, and whole blood, both under agitated and flow conditions. rDV-biofunctionalized silk biomaterials were shown to be blood compatible in terms of platelet and whole blood interactions and the PIII treatment was shown to be an effective and efficient means of covalently immobilizing rDV in its bioactive form. These biomimetic silk biomaterials are a promising platform toward development of silk-based blood-contacting devices for therapeutic, diagnostic, and research applications. STATEMENT OF SIGNIFICANCE: Blood compatible materials are required for the development of therapeutic and diagnostic blood contacting devices as blood-material interactions are a key factor dictating device functionality. In this work, we explored biofunctionalization of silk biomaterials with a recombinantly expressed domain V (rDV) of the human basement membrane proteoglycan perlecan towards the development of blood compatible surfaces. Perlecan and rDV are of interest in vascular device development as they uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions. rDV was covalently immobilized on silk biomaterials using plasma immersion ion implantation (PIII), a new method of immobilizing proteins on silk biomaterials that does not rely on modification of specific amino acids in the silk protein chain. These biomimetic silk biomaterials are a promising platform toward development of silk-based blood-contacting devices for therapeutic, diagnostic, and research applications.
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Fibroínas , Seda , Materiais Biocompatíveis , Biomimética , Proteoglicanas de Heparan Sulfato , HumanosRESUMO
Silk-based materials are widely used in biomaterial and tissue engineering applications due to their cytocompatibility and tunable mechanical and biodegradation properties. Aqueous-based processing techniques have enabled the fabrication of silk into a broad range of material formats, making it a highly versatile material platform across multiple industries. Utilizing the full potential of silk in biomedical applications frequently requires modification of silk's surface properties. Dry surface modification techniques, including irradiation and plasma treatment, offer an alternative to the conventional wet chemistry strategies to modify the physical and chemical properties of silk materials without compromising their bulk properties. While dry surface modification techniques are more prevalent in textiles and sterilization applications, the range of modifications available and resultant changes to silk materials all point to the utility of dry surface modification for the development of new, functional silk biomaterials. Dry surface treatment affects the surface chemistry, secondary structure, molecular weight, topography, surface energy, and mechanical properties of silk materials. This Review describes and critically evaluates the effect of physical dry surface modification techniques, including irradiation and plasma processes, on silk materials and discusses their utility in biomedical applications, including recent examples of modulation of cell/protein interactions on silk biomaterials, in vivo performance of implanted biomaterials, and applications in material biofunctionalization and lithographic surface patterning approaches.
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Materiais Biocompatíveis , Seda , Hidrogéis , Próteses e Implantes , Engenharia TecidualRESUMO
Multifunctional interfaces that promote endothelialisation, suppress the viability of smooth muscle cells (SMCs), prevent the adhesion and activation of platelets, while demonstrating antibacterial activity are of great interest for surface engineering of blood-contacting devices. Here, we report for the first time the high-power pulsed magnetron sputtering (HPPMS)/DC magnetron sputtering (DCMS) co-sputtering of Ti-xCuO coatings that demonstrate this required multifunctionality. The Cu contents and surface chemistry of the coatings are optimized, and the critical role of copper release on the viability of endothelial cells (ECs) and SMCs, platelet adhesion, and antibacterial activities is elucidated. Rutile phase is formed for Ti-xCuO coatings with Cu atomic concentrations in the range of 1.9 to 13.7 at.%. Rutile and nanocrystalline/amorphous structures were determined for the coatings with 16.8 at.% Cu, while an amorphous phase was observed for the coating with 33.9 at.% Cu. The Ti-xCuO coatings with higher Cu contents were more susceptible to corrosion, and the release rates of Cu ions increased with increasing the Cu contents, maintaining a stable releasing state for up to 28 days. The Ti-xCuO coatings with optimum microstructure and Cu contents of 3.1 and 4.2 at.% promoted the viability and proliferation of ECs, suppressed the viability of smooth muscle cells, inhibited the platelet adhesion and activation, and showed excellent antibacterial activities. Such multifunctionality was achieved in one-pot through controlled copper ions release in the presence of titanium oxides such as TiO2 and Ti2O3 on the surface. The Ti-xCuO coatings developed through HPPMS/DCMS co-sputtering are attractive for surface modification of blood-contacting materials such as implantable cardiovascular devices.
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Materiais Revestidos Biocompatíveis , Titânio , Materiais Revestidos Biocompatíveis/farmacologia , Cobre , Corrosão , Células Endoteliais , Titânio/farmacologiaRESUMO
Three-dimensional (3D) bioprinting, where cells, hydrogels, and structural polymers can be printed layer by layer into complex designs, holds great promise for advances in medicine and the biomedical sciences. In principle, this technique enables the creation of highly patient-specific disease models and biomedical implants. However, an ability to tailor surface biocompatibility and interfacial bonding between printed components, such as polymers and hydrogels, is currently lacking. Here we demonstrate that an atmospheric pressure plasma jet (APPJ) can locally activate polymeric surfaces for the reagent-free covalent attachment of proteins and hydrogel in a single-step process at desired locations. Polyethylene and poly-ε-caprolactone were used as example polymers. Covalent attachment of the proteins and hydrogel was demonstrated by resistance to removal by rigorous sodium dodecyl sulfate washing. The immobilized protein and hydrogel layers were analyzed using Fourier transform infrared and X-ray photoelectron spectroscopy. Importantly, the APPJ surface activation also rendered the polymer surfaces mildly hydrophilic as required for optimum biocompatibility. Water contact angles were observed to be stable within a range where the conformation of biomolecules is preserved. Single and double electrode designs of APPJs were compared in their characteristics relevant to localized surface functionalization, plume length, and shape. As a proof of efficacy in a biological context, APPJ-treated polyethylene functionalized with fibronectin was used to demonstrate improvements in cell adhesion and proliferation. These results have important implications for the development of a new generation of 3D bioprinters capable of spatially patterned and tailored surface functionalization performed during the 3D printing process in situ.
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Materiais Biocompatíveis/química , Bioimpressão/métodos , Gases em Plasma/química , Polímeros/química , Animais , Pressão Atmosférica , Materiais Biocompatíveis/farmacologia , Bovinos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Eletrodos , Humanos , Hidrogéis/química , Impressão Tridimensional , Soroalbumina Bovina/química , Propriedades de Superfície , MolhabilidadeRESUMO
The rise of additive manufacturing has provided a paradigm shift in the fabrication of precise, patient-specific implants that replicate the physical properties of native bone. However, eliciting an optimal biological response from such materials for rapid bone integration remains a challenge. Here we propose for the first time a one-step ion-assisted plasma polymerization process to create bio-functional 3D printed titanium (Ti) implants that offer rapid bone integration. Using selective laser melting, porous Ti implants with enhanced bone-mimicking mechanical properties were fabricated. The implants were functionalized uniformly with a highly reactive, radical-rich polymeric coating generated using a unique combination of plasma polymerization and plasma immersion ion implantation. We demonstrated the performance of such activated Ti implants with a focus on the coating's homogeneity, stability, and biological functionality. It was shown that the optimized coating was highly robust and possessed superb physico-chemical stability in a corrosive physiological solution. The plasma activated coating was cytocompatible and non-immunogenic; and through its high reactivity, it allowed for easy, one-step covalent immobilization of functional biomolecules in the absence of solvents or chemicals. The activated Ti implants bio-functionalized with bone morphogenetic protein 2 (BMP-2) showed a reduced protein desorption and a more sustained osteoblast response both in vitro and in vivo compared to implants modified through conventional physisorption of BMP-2. The versatile new approach presented here will enable the development of bio-functionalized additively manufactured implants that are patient-specific and offer improved integration with host tissue. STATEMENT OF SIGNIFICANCE: Additive manufacturing has revolutionized the fabrication of patient-specific orthopedic implants. Although such 3D printed implants can show desirable mechanical and mass transport properties, they often require surface bio-functionalities to enable control over the biological response. Surface covalent immobilization of bioactive molecules is a viable approach to achieve this. Here we report the development of additively manufactured titanium implants that precisely replicate the physical properties of native bone and are bio-functionalized in a simple, reagent-free step. Our results show that covalent attachment of bone-related growth factors through ion-assisted plasma polymerized interlayers circumvents their desorption in physiological solution and significantly improves the bone induction by the implants both in vitro and in vivo.
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Biomimética , Próteses e Implantes , Humanos , Osteoblastos , Porosidade , Titânio/farmacologiaRESUMO
Ti-xCu coatings with varied Cu contents were deposited by hybrid HiPIMS/DC magnetron co-sputtering to achieve optimum microstructures and surface chemistries for applications as multi-functional, blood-contacting interfaces. We have demonstrated that control over the chemistry and microstructure of the coatings provides interfaces that simultaneously exhibit antibacterial properties, show endothelial cell (EC) compatibility, and prevent smooth muscle cell (SMC) proliferation. Using XRD and HRTEM analyses, we identified distinct microstructures for coatings with various Cu/(Cuâ¯+â¯Ti) atomic concentrations. The corrosion resistance was controlled by the microstructure of the Ti-xCu coatings and decreased with increases in the Cu atomic concentration. XPS and ICP-MS results provided evidence that copper ions are released from the coatings upon immersion in PBS solution. We have demonstrated that the Cu-containing phases are weak points that are attacked and corroded easily, resulting in the release of Cu ions from the coatings. The coatings with Cu/(Tiâ¯+â¯Cu) ratios ranging from 3 to 65 at.% inhibited the viability of SMCs significantly. The optimized coating with Ti and Cu/CuTix crystals and Cu/(Tiâ¯+â¯Cu) ratio of 16 at.% showed significant improvements in EC compatibility as well as reduced viability of SMCs, holding great promise for the surface modification of cardiovascular devices such as stents and coronary implants. The coatings with amorphous phases and Cu/(Tiâ¯+â¯Cu) ratios of 55 and 65 at.% showed excellent antibacterial properties against Staphylococcus aureus bacteria. The coating with 55.0 at.% Cu is an encouraging material for the surface engineering of blood-contacting implant surfaces that have antibacterial properties but are not cytotoxic to SMCs.
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Sistema Cardiovascular/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Propriedades de Superfície/efeitos dos fármacos , Titânio/química , Titânio/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Corrosão , Células Endoteliais da Veia Umbilical Humana , Humanos , Teste de Materiais/métodos , Miócitos de Músculo Liso/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
The growing applications of electrochromic (EC) devices have generated great interest in bifunctional materials that can serve as both transparent conductive (TC) and EC coatings. WO3/Ag/WO3 (WAW) heterostructures, in principle, facilitate this extension of EC technology without reliance on an indium tin oxide (ITO) substrate. However, these structures synthesized using traditional methods have shown significant performance deficiencies. Thermally evaporated WAW structures show weak adhesion to the substrate with rapid degradation of coloration efficiency. Improved EC durability can be obtained using magnetron sputtering deposition, but this requires the insertion of an extra tungsten (W) sacrificial layer beneath the external WO3 layer to prevent oxidation and associated loss of conductivity of the silver film. Here, we demonstrate for the first time that a new method, known as high-power impulse magnetron sputtering (HiPIMS), can produce trilayer bifunctional EC and TC devices, eliminating the need for the additional protective layer. X-ray photoelectron spectroscopy and X-ray diffraction data provided evidence that oxidation of the silver layer can be avoided, whilst stoichiometric WO3 structures are achieved. To achieve optimum WAW structures, we tuned the partial pressure of oxygen in the HiPIMS atmosphere applied for the deposition of WO3 layers. Our optimized WO3 (30 nm)/Ag (10 nm)/WO3 (50 nm) structure had a sheet resistance of 23.0 ± 0.4 Ω/â¡ and a luminous transmittance of 80.33 ± 0.07%. The HiPIMS coatings exhibited excellent long-term cycling stability for at least 2500 cycles, decent switching times (bleaching: 22.4 s, coloring: 15 s), and luminescence transmittance modulation (Δ T) of 34.5%. The HiPIMS strategy for the fabrication of ITO-free EC coatings for smart windows holds great promise to be extended to producing other metal-dielectric composite coatings for modern applications such as organic light-emitting diodes (OLEDs), liquid crystals, and wearable displays.
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Cardiovascular disease is an inflammatory disorder that may benefit from appropriate modulation of inflammation. Systemic treatments lower cardiac events but have serious adverse effects. Localized modulation of inflammation in current standard treatments such as bypass grafting may more effectively treat CAD. The present study investigated a bioactive vascular graft coated with the macrophage polarizing cytokine interleukin-4. These grafts repolarize macrophages to anti-inflammatory phenotypes, leading to modulation of the pro-inflammatory microenvironment and ultimately to a reduction of foreign body encapsulation and inhibition of neointimal hyperplasia development. These resulting functional improvements have significant implications for the next generation of synthetic vascular grafts.
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Silk fibroin isolated from Bombyx mori cocoons is a promising material for a range of biomedical applications, but it has no inherent cell-interactive domains, necessitating functionalization with bioactive molecules. Here we demonstrate significantly enhanced cell interactions with silk fibroin biomaterials in the absence of biofunctionalization following surface modification using plasma immersion ion implantation (PIII). Further, PIII treated silk fibroin biomaterials supported direct covalent immobilization of proteins on the material surface in the absence of chemical cross-linkers. Surface analysis after nitrogen plasma and PIII treatment at 20 kV revealed that the silk macromolecules are significantly fragmented, and at the higher fluences of implanted ions, surface carbonization was observed to depths corresponding to that of the ion penetration. Consistent with the activity of radicals created in the treated surface layer, oxidation was observed on contact with atmospheric oxygen and the PIII treated surfaces were capable of direct covalent immobilization of bioactive macromolecules. Changes in thickness, amide and nitrile groups, refractive index, and extinction coefficient in the wavelength range 400-1000 nm as a function of ion fluence are presented. Reactions responsible for the restructuring of the silk surface under ion beam treatment that facilitate covalent binding of proteins and a significant improvement in cell interactions on the modified surface are proposed.
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Seda , Animais , Materiais Biocompatíveis , Bombyx , Fibroínas , Íons , Próteses e ImplantesRESUMO
Surface functionalization of an implantable device with bioactive molecules can overcome adverse biological responses by promoting specific local tissue integration. Bioactive peptides have advantages over larger protein molecules due to their robustness and sterilizability. Their relatively small size presents opportunities to control the peptide orientation on approach to a surface to achieve favourable presentation of bioactive motifs. Here we demonstrate control of the orientation of surface-bound peptides by tuning electric fields at the surface during immobilization. Guided by computational simulations, a peptide with a linear conformation in solution is designed. Electric fields are used to control the peptide approach towards a radical-functionalized surface. Spontaneous, irreversible immobilization is achieved when the peptide makes contact with the surface. Our findings show that control of both peptide orientation and surface concentration is achieved simply by varying the solution pH or by applying an electric field as delivered by a small battery.
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Materiais Biocompatíveis/química , Proteínas Imobilizadas/química , Peptídeos/química , Titânio/química , Adsorção , Sequência de Aminoácidos , Eletricidade , Eletrodos Implantados , Humanos , Concentração de Íons de Hidrogênio , Neuroestimuladores Implantáveis , Propriedades de SuperfícieRESUMO
Osseointegration is essential for ensuring optimal functioning and longevity of orthopedic implants. In a significant number of patients, the body does not fully integrate with the orthopedic implant, which opens the potential for the formation of bacterial biofilms and adverse foreign body reactions. Protein-functionalization of the implant surfaces can reduce this potential by stimulating rapid cell attachment or bone formation. Ideally, a multifunctional protein surface should simultaneously stimulate cell attachment and bone formation for optimal osseointegration. In this study, we utilized primary mouse osteoblasts to examine the osteogenic potential of a multifunctional fusion protein, combining the fibronectin (FN) attachment and osteocalcin (OCN) bone signaling sequences, compared against that of the individual proteins. These three biomolecules were immobilized on radical-functionalized plasma polymer films (rPPFs) that covalently bond proteins through interactions with embedded radicals that migrate to the surface. The fusion protein was also compared to a coimmobilized ratio of FN:OCN prepared through a two-step sequential exposure to OCN solution followed by FN solution. The preparation and characterization overhead for the two protein surfaces was substantial when compared to the fusion protein functionalization process. Significantly greater osteoblast attachment and spreading were observed for the FN, FN:OCN, and fusion protein surfaces compared to titanium (p < 0.05), while the calcium deposition after 17 days showed a significant increase (p < 0.01) on the fusion protein surface alone. The greater osseointegration potential of the fusion protein surface compared to the single and coimmobilized protein surfaces is attributed to the homogeneous distribution of the attachment and signaling sequences. Overall, the fusion protein-coated rPPFs produced easily functionalizable and highly osteogenic surfaces with the potential to greatly improve the tissue integration of orthopedic implants.