Enhanced Antibacterial Ability of Electrospun PCL Scaffolds Incorporating ZnO Nanowires.

The infection of implanted biomaterial scaffolds presents a major challenge. Existing therapeutic solutions, such as antibiotic treatment and silver nanoparticle-containing scaffolds are becoming increasingly impractical because of the growth of antibiotic resistance and the toxicity of silver nanoparticles. We present here a novel concept to overcome these limitations, an electrospun polycaprolactone (PCL) scaffold functionalised with zinc oxide nanowires (ZnO NWs). This study assessed the antibacterial capabilities and biocompatibility of PCL/ZnO scaffolds. The fabricated scaffolds were characterised by SEM and EDX, which showed that the ZnO NWs were successfully incorporated and distributed in the electrospun PCL scaffolds. The antibacterial properties were investigated by co-culturing PCL/ZnO scaffolds with Staphylococcus aureus. Bacterial colonisation was reduced to 51.3% compared to a PCL-only scaffold. The biocompatibility of the PCL/ZnO scaffolds was assessed by culturing them with HaCaT cells. The PCL scaffolds exhibited no changes in cell metabolic activity with the addition of the ZnO nanowires. The antibacterial and biocompatibility properties make PCL/ZnO a good choice for implanted scaffolds, and this work lays a foundation for ZnO NWs-infused PCL scaffolds in the potential clinical application of tissue engineering.

Mucoadhesive Electrospun Patch Delivery of Lidocaine to the Oral Mucosa and Investigation of Spatial Distribution in a Tissue Using MALDI-Mass Spectrometry Imaging.

Many oral mucosal conditions cause considerable and prolonged pain that to date has been difficult to alleviate via topical delivery, and the use of injection causes many patients dental anxiety and needle-prick pain. Therefore, developing a noninjectable drug delivery system as an alternative administration procedure may vastly improve the health and wellbeing of these patients. Recent advances in the development of mucoadhesive electrospun patches for the direct delivery of therapeutics to the oral mucosa offer a potential solution, but as yet, the release of local anesthetics from this system and their uptake by oral tissue have not been demonstrated. Here, we demonstrate the fabrication of lidocaine-loaded electrospun fiber patches, drug release, and subsequent uptake and permeation through the porcine buccal mucosa. Lidocaine HCl and lidocaine base were incorporated into the electrospun patches to evaluate the difference in drug permeation for the two drug compositions. Lidocaine released from the lidocaine HCl-containing electrospun patches was significantly quicker than from the lidocaine base patches, with double the amount of drug released from the lidocaine HCl patches in the first 15 min (0.16 ± 0.04 mg) compared to that from the lidocaine base patches (0.07 ± 0.01 mg). The permeation of lidocaine from the lidocaine HCl electrospun patches through ex vivo porcine buccal mucosa was also detected in 15 min, whereas permeation of lidocaine from the lidocaine base patch was not detected. Matrix-assisted laser desorption ionization-mass spectrometry imaging was used to investigate localization of lidocaine within the oral tissue. Lidocaine in the solution as well as from the mucoadhesive patch penetrated into the buccal mucosal tissue in a time-dependent manner and was detectable in the lamina propria after only 15 min. Moreover, the lidocaine released from lidocaine HCl electrospun patches retained biological activity, inhibiting veratridine-mediated opening of voltage-gated sodium channels in SH-SY5Y neuroblastoma cells. These data suggest that a mucoadhesive electrospun patch may be used as a vehicle for rapid uptake and sustained anesthetic drug delivery to treat or prevent oral pain.

An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering.

Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function.

Electrospinning polymersomes into bead-on-string polyethylene oxide fibres for the delivery of biopharmaceuticals to mucosal epithelia.

Fibrous mucoadhesive polymer membranes prepared using electrospinning demonstrate many advantages for mucosal drug delivery compared to other formulations. Previous electrospun membrane formulations have been developed mainly for the delivery of small molecule drugs. There remains great potential to further develop the technology for the delivery of vesicular vectors that allow administration of advanced therapeutic agents. However, there are no previous reports demonstrating the release of intact drug delivery vesicles from electrospun materials. Here, we describe incorporation and release of protein-loaded polymersomes from polyethylene oxide (PEO)-based electrospun membranes. Polymersomes comprising a copolymer of glycerol monomethacrylate (GMA) and hydroxypropyl methacrylate (HPMA) were prepared using polymerization-induced self-assembly and incorporated within PEO membranes using bead-on-string electrospinning at approximately 40 % w/w by polymer mass. Super-resolution fluorescence imaging showed that the vesicles remained intact and retained their encapsulated protein load within the fibre beads. Transmission electron microscopy and dynamic light scattering demonstrated that polymersomes retained their morphology following release from the polymer fibres. F(ab) antibody fragments were encapsulated within polymersomes and then electrospun into membranes. 78 ± 13 % of the F(ab) remained encapsulated within polymersomes during electrospinning and retained functionality when released from electrospun membranes, demonstrating that the formulation is suitable for the delivery of biologics. Membranes were non-irritant to the oral epithelium and fluorescence microscopy detected accumulation of polymersomes within the epithelia following application. This innovative drug delivery approach represents a novel and potentially highly useful method for the administration of large molecular mass therapeutic molecules to diseased mucosal sites.

The safety and biocompatibility of direct aesthetic restorative materials.

Restorative dental materials are among the most important medical devices in terms of the numbers of patients who benefit and the technical sophistication of the products. Many though contain toxic or noxious substances, including potentially sensitising resin monomers, photoinitiators, acidic polymers and glass or ceramic filler particles. Despite this, dental materials are among the safest medical devices in use today, with very few reports of adverse reactions or injuries among both patients or the dental team. This paper considers the potential for adverse reactions to dental materials, current evidence for harm and finally examines the reasons why in real-world clinical use the likelihood of an adverse event is extremely low. Medical devices regulations, responsible manufacture and clinical vigilance all appear to play important roles in ensuring that dental materials do not cause or present a risk to patients. While this excellent in-practice safety record is welcome, there is now increasing interest in the 'macro' scale biocompatibility of dental materials and their packaging in the environment, subjects that have been relatively neglected until recently. It was concluded that this should be a priority for future research and development and support is needed from governments alongside the manufacturing industry and the profession.

Resin-based composite materials: elution and pollution.

Pollution arises from all human activity and the provision of oral healthcare using resin-based composite restorative materials (RBCs) should be considered. This paper aims to provide a comprehensive review of the potential pollutant risk to the environment from the chemical compounds found in resin-based restorative materials, by including: 1) the principal pollutant compounds present in the resin matrix; 2) the degradation process of RBCs and its consequences; 3) the methods used for the detection and quantification of monomer elution and RBC microparticles; and 4) a review of the release mechanisms of eluates and RBC microparticles into the environment.RBCs are pollutants by virtue of the compounds created during the degradation processes. These are in the form of the constituent eluted monomers and microparticles. Their impact on the environment and biodiversity is unknown. These materials are currently one of the main direct-placement restorative materials and their success is unquestionable when used and maintained correctly. Mitigation strategies for reducing the impact of pollution on the environment should be considered and implemented by all stakeholders and processes in the supply chain, from manufacturing, clinical use and waste management.

Quantification of single use plastics waste generated in clinical dental practice and hospital settings.

OBJECTIVES: To quantify (by number and mass) single use plastic waste generated from the provision of oral healthcare in primary and secondary care clinical dental settings in the UK. METHODS: An observational study of four dental practices and the clinics of a UK undergraduate dental teaching hospital was conducted. A range of routine common procedures were observed by trained and calibrated observers; these were: Examinations, endodontics, periodontics, direct placement restorations, fixed and removable prosthodontics and oral surgery. The PPE items used before and during the COVID-19 pandemic were also included. RESULTS: Routine 'surgery set up' generic items present a significant proportion of SUP plastic waste as these are used in every instance of patient treatment. An average of twenty-one (n = 21) SUP plastic waste items are used for every procedure with a mean mass of 354 g per procedure (including set up and clean up). The use of PPE increased from 14 items (pre-COVID -19) to 19 items during the pandemic. SUP items are constructed from a single plastic or from multiple plastics forming compound structures (heteropolymers); with an approximate 50:50 distribution. CONCLUSIONS: The dental profession, at the point of care, uses a high volume of single use plastic that becomes clinical waste. The use of personal protective equipment (PPE) significantly increased during the COVID 19 pandemic and this accounts for the single greatest contribution of single use plastic, as this is used for every clinical procedure. CLINICAL SIGNIFICANCE: Manufacturers, distributors and oral healthcare providers have an opportunity to consider and implement approaches that include effective waste management with reduction, recovery and recycling at its core, towards transforming oral healthcare to a circular plastics economy.

In vitro biocompatibility of modified potassium fluorrichterite and potassium fluorrichterite-fluorapatite glass-ceramics.

Potassium fluorrichterite (KNaCaMg(5)Si(8)O(22)F(2)) glass-ceramics were modified by either increasing the concentration of calcium in the glass (GC5), or by the addition of P(2)O(5) to produce potassium fluorrichterite-fluorapatite (GP2). The solubility of the stoichiometric composition (GST), GC5 and GP2 were measured using the standard test described in ISO 6872:1995 (Dental Ceramics). Ion release profiles were determined for Si, Ca, Mg, Na, K and P using inductively coupled plasma mass spectrometry and fluoride ion (F(-)) concentration was measured using an ion-selective electrode. The cytotoxicity of all compositions was assessed using cultured rat osteosarcoma cells (ROS, 17/2.8). Cell response was qualitatively assessed using scanning electron microscopy (SEM) and quantitatively using the Alamar blue assay. GST was the least soluble and also released the lowest concentration of ions following immersion in water. Of the modified compositions, GC5 demonstrated intermediate solubility but the greatest ion release while GP2 exhibited the highest solubility. This was most likely due to GC5 having the greatest proportion of residual glass following crystallisation. The mass loss exhibited by GP2 may have been due in part to the partial disintegration of the surface of specimens during solubility testing. SEM demonstrated that all compositions supported the growth of healthy ROS cells on their surfaces, and this data was further supported by the quantitative Alamar blue assay.

The antimicrobial activity and biocompatibility of a controlled gentamicin-releasing single-layer sol-gel coating on hydroxyapatite-coated titanium.

AIMS: The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. METHODS: Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. RESULTS: The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. CONCLUSION: In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522-529.

Prediction of osteoconductive activity of modified potassium fluorrichterite glass-ceramics by immersion in simulated body fluid.

Potassium fluorrichterite (KNaCaMg(5)Si(8)O(22)F(2)) glass-ceramics were modified by either increasing the concentration of calcium (GC5) or by the addition of P(2)O(5) (GP2). The stoichiometric composition (GST), GC5 and GP2 were soaked in simulated body fluid (SBF) along with 45S5-type bioglass as a control. After immersion, surface analyses were performed using thin-film X-ray diffraction (TF-XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared (reflection) spectroscopy (FT-IR). All compositions showed the formation of a calcium phosphate rich surface layer in SBF; GST, GP2 and the bioglass control within 7 days of immersion and GC5 after 14 days. It was concluded that all compositions were likely to be osteoconductive in vivo, with GP2 providing the best performance in terms of the combination of rapid formation of the surface layer and superior mechanical properties. This glass-ceramic system has potential as a load bearing bioceramic for fabrication of medical devices intended for skeletal tissue repair.

Electrospun Scaffolds Containing Silver-Doped Hydroxyapatite with Antimicrobial Properties for Applications in Orthopedic and Dental Bone Surgery.

Preventing the development of osteomyelitis while enhancing bone regeneration is challenging, with relatively little progress to date in translating promising technologies to the clinic. Nanoscale hydroxyapatite (nHA) has been employed as a bone graft substitute, and recent work has shown that it may be modified with silver to introduce antimicrobial activity against known pathogens. The aim of this study was to incorporate silver-doped nHA into electrospun scaffolds for applications in bone repair. Silver-doped nHA was produced using a modified, rapid mixing, wet precipitation method at 2, 5, 10 mol.% silver. The silver-doped nHA was added at 20 wt.% to a polycaprolactone solution for electrospinning. Bacteria studies demonstrated reduced bacterial presence, with Escherichia coli and Staphylococcus aureus undetectable after 96 h of exposure. Mesenchymal stem cells (MSCs) were used to study both toxicity and osteogenicity of the scaffolds using PrestoBlue® and alkaline phosphatase (ALP) assays. Innovative silver nHA scaffolds significantly reduced E. coli and S. aureus bacterial populations while maintaining cytocompatibility with mammalian cells and enhancing the differentiation of MSCs into osteoblasts. It was concluded that silver-doped nHA containing scaffolds have the potential to act as an antimicrobial device while supporting bone tissue healing for applications in orthopedic and dental bone surgery.

Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine.

Oral disease greatly affects quality of life, as the mouth is required for a wide range of activities including speech, food and liquid consumption. Treatment of oral disease is greatly limited by the dose forms that are currently available, which suffer from short contact times, poor site specificity, and sensitivity to mechanical stimulation. Mucoadhesive devices prepared using electrospinning offer the potential to address these challenges by allowing unidirectional site-specific drug delivery through intimate contact with the mucosa and with high surface areas to facilitate drug release. This review will discuss the range of electrospun mucoadhesive devices that have recently been reported to address oral inflammatory diseases, pain relief, and infections, as well as new treatments that are likely to be enabled by this technology in the future.

Incorporation of lysozyme into a mucoadhesive electrospun patch for rapid protein delivery to the oral mucosa.

The delivery of biopharmaceuticals to the oral mucosa offers a range of potential applications including antimicrobial peptides to treat resistant infections, growth factors for tissue regeneration, or as an alternative to injections for systemic delivery. Existing formulations targeting this site are typically non-specific and provide little control over dose. To address this, an electrospun dual-layer mucoadhesive patch was investigated for protein delivery to the oral mucosa. Lysozyme was used as a model antimicrobial protein and incorporated into poly(vinylpyrrolidone)/Eudragit RS100 polymer nanofibers using electrospinning from an ethanol/water mixture. The resulting fibrous membranes released the protein at a clinically desirable rate, reaching 90 ± 13% cumulative release after 2 h. Dual fluorescent fibre labelling and confocal microscopy demonstrated the homogeneity of lysozyme and polymer distribution. High encapsulation efficiency and preservation of enzyme activity were achieved (93.4 ± 7.0% and 96.1 ± 3.3% respectively). The released lysozyme inhibited the growth of the oral bacterium Streptococcus ratti, providing further evidence of retention of biological activity and illustrating a potential application for treating and preventing oral infections. An additional protective poly(caprolactone) backing layer was introduced to promote unidirectional delivery, without loss of enzyme activity, and the resulting dual-layer patches displayed long residence times using an in vitro test, showing that the adhesive properties were maintained. This study demonstrates that the drug delivery system has great potential for the delivery of therapeutic proteins to the oral mucosa.

Determination of Polyetheretherketone (PEEK) mechanical properties as a denture material.

PURPOSE: To optimize the gypsum mold temperatures for pressed PEEK, and to estimate the impact, tensile strength and flexural properties of pressed and milled PEEK. Where appropriate, these properties were compared with those of PMMA. MATERIALS AND METHODS: Since the mold temperature could affect the properties of the injected parts, the temperature of 20 gypsum specimens was monitored using the multi-thermocouple system (n = 5). A total of 210 specimens were prepared for mechanical tests according to the ISO standard for denture base polymer (n = 10). The Izod impact, tensile strength, and flexural behavior were assessed. PEEK-OptimaNI1 (PEEK-pressed) was tested after processing via the pressing method at4 different mold temperatures. Machining PEEK-Juvora (PEEK-milled) specimens were prepared using the CAD-CAM production method. Data were analyzed via one-way ANOVA performed at a confidence level of 95% and a significant P-value of (P ≤ 0.05). RESULTS: In comparison to the furnace temperature more heat was required to preheat the gypsum mold up to 100, 150, 175 and 200 °C for pressing purposes. The highest impact strength was 5.7 kJ/m2 for PEEK-pressed at 100 °C mold temperature and 4 kJ/m2 for PEEK-milled. The latter had a higher tensile strength of 118 MPa. The best result for PEEK-pressed was 97 MPa at 200 °C mold temperature. Under a 4-point bending test, Young's modulus of PEEK-milled was 5591 MPa, while the highest for PEEK-pressed was 4936 MPa at 200 °C mold temperature. CONCLUSIONS: Compared to PMMA, given the superior mechanical properties of PEEK, it may become the material of choice for future use. Dentures constructed from PEEK polymer could well be routinely constructed in the near future.

Thermally responsive polymeric hydrogel brushes: synthesis, physical properties and use for the culture of chondrocytes.

Hydrogel brushes are materials composed of a water-swollen network, which contains polymer chains that are grafted with another polymer. Using a thermally responsive polymer, poly(N-isopropyl acrylamide) (polyNIPAM), as the graft component we are able to maintain the critical solution temperature (Tcrit), independent of the overall composition of the material, at approximately 32 degrees C. The change in swelling at Tcrit is a function of the amount of polyNIPAM in the system. However, there is a much smaller change in the surface contact angles at Tcrit. PolyNIPAM-based materials have generated considerable interest, as 'smart' substrates for the culture of cells and here, we show the utility of hydrogel brushes in cell culture. Chondrocytes attached to the hydrogel brushes and yielded viable cell cultures. Moreover, the chondrocytes could be released from the hydrogel brushes without the use of proteases by reducing the temperature of the cultures to below Tcrit to induce a change in the conformation of the polyNIPAM chain at Tcrit. The importance of the crosslink hydrogel component is illustrated by significant changes in cell attachment/cell viability as the crosslink density is changed.

Rapid Mix Preparation of Bioinspired Nanoscale Hydroxyapatite for Biomedical Applications.

Hydroxyapatite (HA) has been widely used as a medical ceramic due to its good biocompatibility and osteoconductivity. Recently there has been interest regarding the use of bioinspired nanoscale hydroxyapatite (nHA). However, biological apatite is known to be calcium-deficient and carbonate-substituted with a nanoscale platelet-like morphology. Bioinspired nHA has the potential to stimulate optimal bone tissue regeneration due to its similarity to bone and tooth enamel mineral. Many of the methods currently used to fabricate nHA both in the laboratory and commercially, involve lengthy processes and complex equipment. Therefore, the aim of this study was to develop a rapid and reliable method to prepare high quality bioinspired nHA. The rapid mixing method developed was based upon an acid-base reaction involving calcium hydroxide and phosphoric acid. Briefly, a phosphoric acid solution was poured into a calcium hydroxide solution followed by stirring, washing and drying stages. Part of the batch was sintered at 1,000 °C for 2 h in order to investigate the products' high temperature stability. X-ray diffraction analysis showed the successful formation of HA, which showed thermal decomposition to ß-tricalcium phosphate after high temperature processing, which is typical for calcium-deficient HA. Fourier transform infrared spectroscopy showed the presence of carbonate groups in the precipitated product. The nHA particles had a low aspect ratio with approximate dimensions of 50 x 30 nm, close to the dimensions of biological apatite. The material was also calcium deficient with a Ca:P molar ratio of 1.63, which like biological apatite is lower than the stoichiometric HA ratio of 1.67. This new method is therefore a reliable and far more convenient process for the manufacture of bioinspired nHA, overcoming the need for lengthy titrations and complex equipment. The resulting bioinspired HA product is suitable for use in a wide variety of medical and consumer health applications.

The Effect of RANKL/OPG Balance on Reducing Implant Complications.

Despite the phenomenal success of implants particularly in the realms of dentistry and orthopaedics, there are still challenges to overcome. The failure of implants resulting from infection, prosthetic loosening, and non-union continue to be the most notorious examples. The cascade of fracture healing and bone repair, especially with the presence of an implant, is complex because it involves a multifaceted immune response alongside the intricate process of bone formation and remodelling. Bone loss is a serious clinical problem that is frequently accompanied by chronic inflammation, illustrating that there is a convoluted relationship between inflammation and bone erosion. The effects of pro-inflammatory factors play a significant role in initiating and maintaining osteoclastogenesis that results in bone resorption by osteoclasts. This is because there is a disruption of the relative ratio between Receptor Activator of Nuclear Factor κB-Ligand (RANKL) and osteoprotegerin (OPG), which is central to modulating bone repair and remodelling. This review aims to provide a background to the bone remodelling process, the bone repair cascade post-implantation, and the associated complications. Furthermore, current clinical solutions that can influence bone formation via either internal or extrinsic mechanisms will be described. These efficacious treatments for osteolysis via targeting the RANKL/OPG ratio may be crucial to reducing the incidence of related implant failures in the future.

Multifunctional bioactive glass and glass-ceramic biomaterials with antibacterial properties for repair and regeneration of bone tissue.

Bioactive glasses (BGs) and related glass-ceramic biomaterials have been used in bone tissue repair for over 30years. Previous work in this field was comprehensively reviewed including by their inventor Larry Hench, and the key features and properties of BGs are well understood. More recently, attention has focused on their modification to further enhance the osteogenic behaviour, or further compositional changes that may introduce additional properties, such as antimicrobial activity. Evidence is emerging that BGs and related glass-ceramics may be modified in such a way as to simultaneously introduce more than one desirable property. The aim of this review is therefore to consider the evidence that these more recent inorganic modifications to glass and glass-ceramic biomaterials are effective, and whether or not these new compositions represent sufficiently versatile systems to underpin the development of a new generation of truly multifunctional biomaterials to address pressing clinical needs in orthopaedic and dental surgery. Indeed, a number of classical glass compositions exhibited antimicrobial activity, however the structural design and the addition of specific ions, i.e. Ag+, Cu+, and Sr2+, are able to impart a multifunctional character to these systems, through the combination of, for example, bioactivity with bactericidal activity. STATEMENT OF SIGNIFICANCE: In this review we demonstrate the multifunctional potential of bioactive glasses and related glass-ceramics as biomaterials for orthopaedic and craniofacial/dental applications. Therefore, it considers the evidence that the more recent inorganic modifications to glass and glass-ceramic biomaterials are able to impart antimicrobial properties alongside the more classical bone bonding and osteoconduction. These properties are attracting a special attention nowadays that bacterial infections are an increasing challenge in orthopaedics. We also focus the manuscript on the versatility of these systems as a basis to underpin the development of a new generation of truly multifunctional biomaterials to address pressing clinical needs in orthopaedic, craniofacial and dental surgery.

Multilayer Nanoscale Encapsulation of Biofunctional Peptides to Enhance Bone Tissue Regeneration In Vivo.

Bone tissue healing is a dynamic process that is initiated by the recruitment of osteoprogenitor cells followed by their migration, proliferation, differentiation, and development of a mineralizing extracellular matrix. The work aims to manufacture a functionalized porous membrane that stimulates early events in bone healing for initiating a regenerative cascade. Layer-by-layer (LbL) assembly is proposed to modify the surface of osteoconductive electrospun meshes, based on poly(lactic-co-glycolic acid) and nanohydroxyapatite, by using poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) as polyelectrolytes. Molecular cues are incorporated by grafting peptide fragments into the discrete nanolayers. KRSR (lysine-arginine-serine-arginine) sequence is grafted to enhance cell adhesion and proliferation, NSPVNSKIPKACCVPTELSAI to guide bone marrow mesenchymal stem cells differentiation in osteoblasts, and FHRRIKA (phenylalanine-histidine-arginine-arginine-isoleucine-lysine-alanine) to improve mineralization matrix formation. Scanning electron microscopy, infrared spectroscopy, and X-ray photoelectron spectroscopy demonstrate the successful surface functionalization. Furthermore, the peptide incorporation enhances cellular processes, with good viability and significant increase of alkaline phosphatase activity, osteopontin, and osteocalcin. The functionalized membrane induces a favorable in vivo response after implantation for four weeks in nonhealing rat calvarial defect model. It is concluded that the multilayer nanoencapsulation of biofunctional peptides using LbL approach has significant potential as innovative manufacturing technique to improve bone regeneration in orthopedic and craniofacial medical devices.

Selective laser melting-enabled electrospinning: Introducing complexity within electrospun membranes.

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing.