Inert Biomaterials Research Articles

Three-Dimensional Electrically Conductive Scaffolds to Culture Cardiac Progenitor Cells.

Three-dimensional (3D) scaffolds provide cell support while improving tissue regeneration through amplified cellular responses between implanted materials and native tissues. So far, highly conductive cardiac, nerve, and muscle tissues have been engineered by culturing stem cells on electrically inert scaffolds. These scaffolds, even though suitable, may not be very useful compared to the results shown by cells when cultured on conductive scaffolds. Noticing the mature phenotype the stem cells develop over time when cultured on conductive scaffolds, scientists have been trying to impart conductivity to traditionally nonconductive scaffolds. One way to achieve this goal is to blend conductive polymers (polyaniline, polypyrrole, PEDOT:PSS) with inert biomaterials and produce a 3D scaffold using various fabrication techniques. One such technique is projection micro-stereolithography, which is an additive manufacturing technique. It uses a photosensitive solution blended with conductive polymers and uses visible/UV light to crosslink the solution. 3D scaffolds with complex architectural features down to microscale resolution can be printed with this technique promptly. This chapter reports a protocol to fabricate electrically conductive scaffolds using projection micro-stereolithography.

Angiogenic and immunomodulation role of ions for initial stages of bone tissue regeneration.

It is widely known that bone has intrinsic capacity to self-regenerate after injury. However, the physiological regeneration process can be impaired when there is an extensive damage. One of the main reasons is due to the inability to establish a new vascular network that ensures oxygen and nutrient diffusion, leading to a necrotic core and non-junction of bone. Initially, bone tissue engineering (BTE) emerged to use inert biomaterials to just fill bone defects, but it eventually evolved to mimic bone extracellular matrix and even stimulate bone physiological regeneration process. In this regard, the stimulation of osteogenesis has gained a lot of attention especially in the proper stimulation of angiogenesis, being critical to achieve a successful osteogenesis for bone regeneration. Besides, the immunomodulation of a pro-inflammatory environment towards an anti-inflammatory one upon scaffold implantation has been considered another key process for a proper tissue restoration. To stimulate these phases, growth factors and cytokines have been extensively used. Nonetheless, they present some drawbacks such as low stability and safety concerns. Alternatively, the use of inorganic ions has attracted higher attention due to their higher stability and therapeutic effects with low side effects. This review will first focus in giving fundamental aspects of initial bone regeneration phases, focusing mainly on inflammatory and angiogenic ones. Then, it will describe the role of different inorganic ions in modulating the immune response upon biomaterial implantation towards a restorative environment and their ability to stimulate angiogenic response for a proper scaffold vascularization and successful bone tissue restoration. STATEMENT OF SIGNIFICANCE: The impairment of bone tissue regeneration when there is excessive damage has led to different tissue engineered strategies to promote bone healing. Significant importance has been given in the immunomodulation towards an anti-inflammatory environment together with proper angiogenesis stimulation in order to achieve successful bone regeneration rather than stimulating only the osteogenic differentiation. Ions have been considered potential candidates to stimulate these events due to their high stability and therapeutic effects with low side effects compared to growth factors. However, up to now, no review has been published assembling all this information together, describing individual effects of ions on immunomodulation and angiogenic stimulation, as well as their multifunctionality or synergistic effects when combined together.

Promoted Abutment-Soft Tissue Integration Around Self-Glazed Zirconia Surfaces with Nanotopography Fabricated by Additive 3D Gel Deposition.

Improving the biological sealing around dental abutments could promote the long-term success of implants. Although titanium abutments have a wide range of clinical applications, they incur esthetic risks due to their color, especially in the esthetic zone. Currently, zirconia has been applied as an esthetic alternative material for implant abutments; however, zirconia is purported to be an inert biomaterial. How to improve the biological activities of zirconia has thus become a popular research topic. In this study, we presented a novel self-glazed zirconia (SZ) surface with nanotopography fabricated by additive 3D gel deposition and investigated its soft tissue integration capability compared to that of clinically used titanium and polished conventional zirconia surfaces. Three groups of disc samples were prepared for in vitro study and the three groups of abutment samples were prepared for in vivo study. The surface topography, roughness, wettability and chemical composition of the samples were examined. Moreover, we analyzed the effect of the three groups of samples on protein adsorption and on the biological behavior of human gingival keratinocytes (HGKs) and human gingival fibroblasts (HGFs). Furthermore, we conducted an in vivo study in which the bilateral mandibular anterior teeth of rabbits were extracted and replaced with implants and corresponding abutments. The surface of SZ showed a unique nanotopography with nm range roughness and a greater ability to absorb protein. The promoted expression of adhesion molecules in both HGKs and HGFs was observed on the SZ surface compared to the surfaces of Ti and PCZ, while the cell viability and proliferation of HGKs and the number of HGFs adhesion were not significant among all groups. In vivo results showed that the SZ abutment formed strong biological sealing at the abutment-soft tissue interface and exhibited markedly more hemidesmosomes when observed with a transmission electron microscope. These results demonstrated that the novel SZ surface with nanotopography promoted soft tissue integration, suggesting its promising application as a zirconia surface for the dental abutment.

Next-generation biomaterials for dental pulp tissue immunomodulation.

The current standard for treating irreversibly damaged dental pulp is root canal therapy, which involves complete removal and debridement of the pulp space and filling with an inert biomaterial. A regenerative approach to treating diseased dental pulp may allow for complete healing of the native tooth structure and enhance the long-term outcome of once-necrotic teeth. The aim of this paper is, therefore, to highlight the current state of dental pulp tissue engineering and immunomodulatory biomaterials properties, identifying exciting opportunities for their synergy in developing next-generation biomaterials-driven technologies. An overview of the inflammatory process focusing on immune responses of the dental pulp, followed by periapical and periodontal tissue inflammation are elaborated. Then, the most recent advances in treating infection-induced inflammatory oral diseases, focusing on biocompatible materials with immunomodulatory properties are discussed. Of note, we highlight some of the most used modifications in biomaterials' surface, or content/drug incorporation focused on immunomodulation based on an extensive literature search over the last decade. We provide the readers with a critical summary of recent advances in immunomodulation related to pulpal, periapical, and periodontal diseases while bringing light to tissue engineering strategies focusing on healing and regenerating multiple tissue types. Significant advances have been made in developing biomaterials that take advantage of the host's immune system to guide a specific regenerative outcome. Biomaterials that efficiently and predictably modulate cells in the dental pulp complex hold significant clinical promise for improving standards of care compared to endodontic root canal therapy.

Tissue engineering atthe dentin-pulp interface using human treated dentin scaffolds conditioned with DMP1 or BMP2 plasmid DNA-carrying calcium phosphate nanoparticles.

Hard dental tissue pathologies, such as caries, are conventionally managed through replacement by tooth-colored inert biomaterials. Tissue engineering provides novel treatment approaches to regenerate lost dental tissues based on bioactive materials and/or signaling molecules. While regeneration in the form of reparative dentin (osteo-dentin) is feasible, the recapitulation of the tubular microstructure of ortho-dentin and its special features is sidelined. This study characterized in vitro, and in vivo human EDTA-treated, freeze-dried dentin matrices (HTFD scaffolds) conditioned with calcium phosphate nanoparticles (NPs) bearing plasmids encoding dentinogenesis-inducing factors (pBMP2/NPs or pDMP1/NPs). The uptake and transfection efficiency of the synthesized NPs on dental pulp stem cells (DPSCs) increased in a concentration- and time-dependent manner, as evaluated qualitatively by confocal laser microscopy and transmission electron microscopy, and quantitatively by flow cytometry, while, in parallel, cell viability decreased. HTFD scaffolds conditioned with the optimal transfectability-to-viability concentration at 4µg Ca/mL of each of the pBMP2/NPs or pDMP1/NPs preserved high levels of cell viability, evidenced by live/dead staining in vitro and caused no adverse reactions after implantation on C57BL6 mice in vivo. HTFD/NPs constructs induced rapid and pronounced odontogenic shift of the DPSCs, as evidenced by relevant gene expression patterns of RunX2, ALP, BGLAP, BMP-2, DMP-1, DSPP by real-time PCR, and acquirement of polarized meta-mitotic phenotype with cellular protrusions entering the dentinal tubules as visualized by scanning electron microscopy. Taken together, HTFD/NPs constitute a promising tool for customized reconstruction of the ortho-dentin/odontoblastic layer barrier and preservation of pulp vitality. STATEMENT OF SIGNIFICANCE: In clinical dentistry, the most common therapeutic approach for the reconstruction of hard dental tissue defects is the replacement by resin-based restorative materials. Even modern bioactive materials focus on reparative dentinogenesis, leading to amorphous dentin-bridge formation in proximity to the pulp. Therefore, the natural microarchitecture of tubular ortho-dentin is not recapitulated, and the sensory and defensive role of odontoblasts is sidelined. This study approaches the reconstruction at the dentin-pulp interface using a construct of human treated dentin (HTFD) scaffold and plasmid-carrying nanoparticles (NPs) encoding dentinogenic factors (DMP-1 or BMP-2) with excellent in vitro and in vivo properties. As a future perspective, the HTFD/NPs constructs could act as bio-fillings for personalized reconstruction of the dentin-pulp interface.

Immunomodulatory Effects of Endodontic Sealers: A Systematic Review.

Inflammation is a crucial step prior to healing, and the regulatory effects of endodontic materials on the immune response can influence tissue repair. This review aimed to answer whether endodontic sealers can modulate the immune cells and inflammation. An electronic search in Scopus, Web of Science, PubMed, and Google Scholar databases were performed. This systematic review was mainly based on PRISMA guidelines, and the risk of bias was evaluated by SYRCLEs and the Modified CONSORT checklist for in vivo and in vitro studies, respectively. In total, 28 articles: 22 in vitro studies, and six in vivo studies were included in this systematic review. AH Plus and AH 26 can down-regulate iNOS mRNA, while S-PRG sealers can down-regulate p65 of NF-κB pathways to inhibit the production of TNF-α, IL-1, and IL-6. In vitro and in vivo studies suggested that various endodontic sealers exhibited immunomodulatory impact in macrophages polarization and inflammatory cytokine production, which could promote healing, tissue repair, and inhibit inflammation. Since the paradigm change from immune inert biomaterials to bioactive materials, endodontic materials, particularly sealers, are required to have modulatory effects in clinical conditions. New generations of endodontic sealers could hamper detrimental inflammatory responses and maintain periodontal tissue, which represent a breakthrough in biocompatibility and functionality of endodontic biomaterials.

Bioactive inorganic nanomaterials for cancer theranostics.

Bioactive materials are a special class of biomaterials that can react in vivo to induce a biological response or regulate biological functions, thus achieving a better curative effect than traditional inert biomaterials. For cancer theranostics, compared with organic or polymer nanomaterials, inorganic nanomaterials possess unique physical and chemical properties, have stronger mechanical stability on the basis of maintaining certain bioactivity, and are easy to be compounded with various carriers (polymer carriers, biological carriers, etc.), so as to achieve specific antitumor efficacy. After entering the nanoscale, due to the nano-size effect, high specific surface area and special nanostructures, inorganic nanomaterials exhibit unique biological effects, which significantly influence the interaction with biological organisms. Therefore, the research and applications of bioactive inorganic nanomaterials in cancer theranostics have attracted wide attention. In this review, we mainly summarize the recent progress of bioactive inorganic nanomaterials in cancer theranostics, and also introduce the definition, synthesis and modification strategies of bioactive inorganic nanomaterials. Thereafter, the applications of bioactive inorganic nanomaterials in tumor imaging and antitumor therapy, including tumor microenvironment (TME) regulation, catalytic therapy, gas therapy, regulatory cell death and immunotherapy, are discussed. Finally, the biosafety and challenges of bioactive inorganic nanomaterials are also mentioned, and their future development opportunities are prospected. This review highlights the bioapplication of bioactive inorganic nanomaterials.

Smart biomaterials: From 3D printing to 4D bioprinting.

This century is blessed with enhanced medical facilities on the grounds of the development of smart biomaterials. The rise of the four-dimensional (4D) bioprinting technology is a shining example. Using inert biomaterials as the bioinks for the three-dimensional (3D) printing process, static objects that might not be able to mimic the dynamic nature of tissues would be fabricated; by contrast, 4D bioprinting can be used for the fabrication of stimuli-responsive cell-laden structures that can evolve with time and enable engineered tissues to undergo morphological changes in a pre-planned way. For all the aptitude of 4D bioprinting technology in tissue engineering, it is imperative to select suitable stimuli-responsive biomaterials with cell-supporting functionalities and responsiveness; as a result, in this article, recent advances and challenges in smart biomaterials for 4D bioprinting are briefly discussed. An overview perspective concerning the latest developments in 4D-bioprinting is also provided.

Evaluation and improvement of the WWTP performance of an agricultural cooperative by adsorption on inert biomaterial: case of orthophosphate, nitrate and sulfate ions

The study is carried out at the wastewater treatment plant (WWTP) of an agricultural cooperative that operates according to the activated sludge process. Dairy industry is enlisted as one of the top-most industries in the food industry. Dairy wastewater treatment is a big issue as dairy wastewater releases a high amount of chemical oxygen demand, inorganic and organic particles, biological oxygen demand, and nutrients. But, these processes partly degrade wastewater containing fats and nutrients as dairy wastewater. The aim of this study was to evaluate the purification performance of this treatment process. The qualitative analysis of decanted raw wastewater (DRWW) and purified wastewater (PWW) shows that the concentration of orthophosphate, nitrate and sulfate ions is slightly higher. Such contaminated water if not handled appropriately, it pollutes water bodies and largely affects our ecosystem and biodiversity. Hence, our proposal is to improve the WWTP performances by using the adsorption process onto dried Carpobrotus edulis as an inert biomaterial. This adsorption process is recognized as one of the best water treatment techniques, more and more works are oriented towards the search for new materials, cheaper and having a good adsorbent potential. This study opens the path for the use of natural and abundant local material to remove orthophosphate, nitrate and sulfate ions using the C. edulis plant particles shred. The surface micromorphology of the biomaterial was investigated using a scanning electron microscope; while the qualitative element composition was analyzed using energy dispersive X-ray and infrared spectroscopies. The found results of DRWW was about 57% for orthophosphates, 67% for sulfates and 73% for nitrates ions. For PWW, the percentage removal was found to be 62%, 73% and 84% for orthophosphates, sulfates and nitrates respectively. These results indicate that dried C. edulis plant, as an environmentally friendly adsorbent could be recommended for the removal of mineral pollutants. In conclusion, the C. edulis adsorbent can be integrated into the activated sludge process for wastewater treatment after identifying the optimal hydraulic loads, associated sizes, and shapes in continuous operations.

Wear Resistance, Color Stability and Displacement Resistance of Milled PEEK Crowns Compared to Zirconia Crowns under Stimulated Chewing and High-Performance Aging.

Recently, polyetheretherketone (PEEK) has been introduced to the dental market as a high-performance and chemically inert biomaterial. This study aimed to compare the wear resistance, abrasiveness, color stability, and displacement resistance of zirconia and PEEK milled crowns. An ideal tooth preparation of a first maxillary molar was done and scanned by an intraoral scanner to make a digital model. Then, the prosthetic crown was digitally designed on the CAD software, and the STL file was milled in zirconia (CaroZiir S, Carol Zircolite Pvt. Ltd., Gujarat, India) and PEEK (BioHpp, Bredent GmbH, Senden, Germany) crowns using five-axis CNC milling machines. The wear resistance, color stability, and displacement resistance of the milled monolithic zirconia with unfilled PEEK crowns using a chewing simulator with thermocyclic aging (120,000 cycles) were compared. The antagonist wear, material wear, color stability, and displacement were evaluated and compared among the groups using the Wilcoxon–Mann–Whitney U-test. Zirconia was shown to be three times more abrasive than PEEK (p value < 0.05). Zirconia had twice the wear resistance of PEEK (p value < 0.05). Zirconia was more color stable than PEEK (p value < 0.05). PEEK had more displacement resistance than zirconia (p value < 0.05). PEEK offers minimal abrasion, better stress modulation through plastic deformation, and good color stability, which make it a promising alternative to zirconia crown.

Breast Silicone Gel Implants versus Autologous Fat Grafting: Biomaterials and Bioactive Materials in Comparison.

In the last 20 years, surgical procedures in breast remodeling during mammoplasty have been deeply modified with a gradual shifting from an invasive intervention using definitive implants (DIs) to a more conservative autologous fat grafting (AFG). AFG has been used for many years as bioactive material through the Lipofilling technique and as a bioactive scaffold when it was enriched with adipose-derived stem cells (ASCs), while DIs have been considered physiologically inert biomaterials with low toxicity. The paper aimed to compare the breast remodeling results obtained in the DI group (55 patients) for hypoplasia correction with those of the ASC-enhanced AFG group (50 patients), also analyzing the influence of breast and chest deformities (tuberous breast, volume, and nipple–areola complex asymmetry, pectus excavatum and carinatum) in the cosmetic outcome. A retrospective, case-control study was conducted. The pre-operative analysis was performed with an accurate clinical evaluation, a photographic assessment, and an instrumental evaluation based on magnetic resonance imaging, mammography, and ultrasound. Of patients treated with DIs 89% (n = 49) showed excellent cosmetic results after 1 year compared with the patients treated with AFG, who showed the same results in 64% (n = 32) of cases. The naturalness of the results in the AFG group was higher than that in the DI group (p < 0.0001 vs. DI group). DIs and AFG were safe and effective in this case series treated. The AFG group showed more natural results, allowing the treatment of patients with pectus excavatum, while DIs showed the more evident and lasting result.

The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials.

The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

A novel suprachoroidal microinvasive glaucoma implant: in vivo biocompatibility and biointegration

BackgroundA major challenge for any glaucoma implant is their ability to provide long-term intraocular pressure lowering efficacy. The formation of a low-permeability fibrous capsule around the device often leads to obstructed drainage channels, which may impair the drainage function of devices. These foreign body-related limitations point to the need to develop biologically inert biomaterials to improve performance in reaching long-term intraocular pressure reduction. The aim of this study was to evaluate in vivo (in rabbits) the ocular biocompatibility and tissue integration of a novel suprachoroidal microinvasive glaucoma implant, MINIject™ (iSTAR Medical, Wavre, Belgium).ResultsIn two rabbit studies, no biocompatibility issue was induced by the suprachoroidal, ab-externo implantation of the MINIject™ device. Clinical evaluation throughout the 6 post-operative months between the sham and test groups were similar, suggesting most reactions were related to the ab-externo surgical technique used for rabbits, rather than the implant material itself. Histological analysis of ocular tissues at post-operative months 1, 3 and 6 revealed that the implant was well-tolerated and induced only minimal fibroplasia and thus minimal encapsulation around the implant. The microporous structure of the device became rapidly colonized by cells, mostly by macrophages through cell migration, which do not, by their nature, impede the flow of aqueous humor through the device. Time-course analysis showed that once established, pore colonization was stable over time. No fibrosis nor dense connective tissue development were observed within any implant at any time point. The presence of pore colonization may be the process by which encapsulation around the implant is minimized, thus preserving the permeability of the surrounding tissues. No degradation nor structural changes of the implant occurred during the course of both studies.ConclusionsThe novel MINIject™ microinvasive glaucoma implant was well-tolerated in ocular tissues of rabbits, with observance of biointegration, and no biocompatibility issues. Minimal fibrous encapsulation and stable cellular pore colonization provided evidence of preserved drainage properties over time, suggesting that the implant may produce a long-term ability to enhance aqueous outflow.

Bioactivation of zirconia surface with laminin protein coating via plasma etching and chemical modification

Surface modification offers a promising alternative to provide bioactivity to implanted inert biomaterials, improving their integration and performance with living tissues. In this contribution, zirconia has been used as a substrate to investigate the biofunctionalization process, designed to add surface bioactivity to a bioinert biomaterial. We intended to attach laminin-5, known for its ability to bind epithelial cells in soft tissue, to the surface of the extracellular matrix protein. First, the zirconia surface was etched and activated with argon plasma and subsequently it was chemically functionalized with calcium and phosphate ions. Zirconia surface activation was monitored by means of a wettability test, whereas functionalization with calcium and phosphate ions was evaluated by confocal Raman microscopy, Z-potential and X-ray Photoelectron Spectroscopy (XPS). The binding of laminin-5 protein to the zirconia surface was carried out by means of adsorption and confirmed by XPS. Then, we used SEM and AFM to observe a homogeneous covering of globular protein over the zirconia surface. Furthermore, epithelial cell response over zirconia surfaces was assayed to show that biofunctionalized surfaces enhance cell adhesion to a greater extent than substrates without protein coating. Our results indicate how the zirconia surface can be modified using argon plasma, in order to enable its bioactivation with the laminin-5 protein.

Coating Medpor® Implant with Tissue-Engineered Elastic Cartilage.

Inert biomaterials used for auricular reconstruction, which is one of the most challenging and diverse tasks in craniofacial or head and neck surgery, often cause problems such as capsule formation, infection, and skin extrusion. To solve these problems, scaffold consisting of inert biomaterial, high-density polyethylene (Medpor®) encapsulated with neocartilage, biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) was created using a tissue engineering strategy. PLGA scaffold without Medpor® was created to serve as the control. Scaffolds were vacuum-seeded with rabbit chondrocytes, freshly isolated from the ear by enzymatic digestion. Then, cell-seeded scaffolds were implanted subcutaneously in the dorsal pockets of nude mice. After 12 weeks, explants were analyzed by histological, biochemical, and mechanical evaluations. Although the PLGA group resulted in neocartilage formation, the PLGA–Medpor® group demonstrated improved outcome with the formation of well-surrounded cartilage around the implants with higher mechanical strength than the PLGA group, indicating that Medpor® has an influence on the structural strength of engineered cartilage. The presence of collagen and elastin fibers was evident in the histological section in both groups. These results demonstrated a novel method of coating implant material with engineered cartilage to overcome the limitations of using biodegradable scaffold in cartilage tissue regeneration. By utilizing the patient’s own chondrocytes, our proposed method may broaden the choice of implant materials while minimizing side effects and immune reaction for the future medical application.

Osteoimmunomodulatory effects of biomaterial modification strategies on macrophage polarization and bone regeneration.

Biomaterials as bone substitutes are always considered as foreign bodies that can trigger host immune responses. Traditional designing principles have been always aimed at minimizing the immune reactions by fabricating inert biomaterials. However, clinical evidence revealed that those methods still have limitations and many of which were only feasible in the laboratory. Currently, osteoimmunology, the very pioneering concept is drawing more and more attention—it does not simply regard the immune response as an obstacle during bone healing but emphasizes the intimate relationship of the immune and skeletal system, which includes diverse cells, cytokines, and signaling pathways. Properties of biomaterials like topography, wettability, surface charge, the release of cytokines, mediators, ions and other bioactive molecules can impose effects on immune responses to interfere with the skeletal system. Based on the bone formation mechanisms, the designing methods of the biomaterials change from immune evasive to immune reprogramming. Here, we discuss the osteoimmunomodulatory effects of the new modification strategies—adjusting properties of bone biomaterials to induce a favorable osteoimmune environment. Such strategies showed potential to benefit the development of bone materials and lay a solid foundation for the future clinical application.

Substrate Independent Liquid Phase Epitaxy of HKUST‐1 as Anticoagulant and Antimicrobial Coating

AbstractThe effective deposition of metal–organic frameworks on kinds of biomaterials is still challenging and highly desirable. Using polydopamine as the effective nucleation center, HKUST‐1 is successfully prepared on three kinds of inert biomaterials, i.e., titanium oxide film (Ti–O), 316L stainless steel (316L SS), and poly(vinyl chloride) (PVC). Characterization of the surfaces by powder X‐ray diffraction confirm the oriented crystal growth of HKUST‐1 on the polydopamine coated substrates. There are no significant difference in catalytical NO generation and surface copper content of the three samples with HKUST‐1 deposition. All keep a NO release speed of ≈2.5 × 10−10 mol cm−2 min−1, thus platelet activation on the HKUST‐1 modified surfaces are inhibited compared to that of the unmodified ones. Ex vivo test shows thrombi formation is dramatically reduced. The HKUST‐1 coated surfaces elicit 95% reduction in the bacterial attachment of both Staphylococcus aureus and Escherichia coli. The endothelial cells and macrophages culture results support good biocompatibility of the modified surfaces. It provides a promising, facile, and effective approach for surface modification of blood contact biomaterials.

Delayed Injection of a Physically Cross-Linked PNIPAAm-g-PEG Hydrogel in Rat Contused Spinal Cord Improves Functional Recovery.

Spinal cord injury is a main health issue, leading to multiple functional deficits with major consequences such as motor and sensitive impairment below the lesion. To date, all repair strategies remain ineffective. In line with the experiments showing that implanted hydrogels, immunologically inert biomaterials, from natural or synthetic origins, are promising tools and in order to reduce functional deficits, to increase locomotor recovery, and to reduce spasticity, we injected into the lesion area, 1 week after a severe T10 spinal cord contusion, a thermoresponsive physically cross-linked poly(N-isopropylacrylamide)-poly(ethylene glycol) copolymer hydrogel. The effect of postinjury intensive rehabilitation training was also studied. A group of male Sprague–Dawley rats receiving the hydrogel was enrolled in an 8 week program of physical activity (15 min/day, 5 days/week) in order to verify if the combination of a treadmill step-training and hydrogel could lead to better outcomes. The data obtained were compared to those obtained in animals with a spinal lesion alone receiving a saline injection with or without performing the same program of physical activity. Furthermore, in order to verify the biocompatibility of our designed biomaterial, an inflammatory reaction (interleukin-1β, interleukin-6, and tumor necrosis factor-α) was examined 15 days post-hydrogel injection. Functional recovery (postural and locomotor activities and sensorimotor coordination) was assessed from the day of injection, once a week, for 9 weeks. Finally, 9 weeks postinjection, the spinal reflexivity (rate-dependent depression of the H-reflex) was measured. The results indicate that the hydrogel did not induce an additional inflammation. Furthermore, we observed the same significant locomotor improvements in hydrogel-injected animals as in trained saline-injected animals. However, the combination of hydrogel with exercise did not show higher recovery compared to that evaluated by the two strategies independently. Finally, the H-reflex depression recovery was found to be induced by the hydrogel and, albeit to a lesser degree, exercise. However, no recovery was observed when the two strategies were combined. Our results highlight the effectiveness of our copolymer and its high therapeutic potential to preserve/repair the spinal cord after lesion.

Problems of reconstructive cranioplasty after traumatic brain injury in children

Cranial repair after traumatic brain injury in children is still burdened by unsolved problems and controversial issues, mainly due to the high rate of resorption of autologous bone as well as the absence of valid alternative material to replace the autologous bone. Indeed, inert biomaterials are associated to satisfactory results in the short period but bear the continuous risk of complications related to the lack of osteointegration capacity. Biomimetic materials claiming osteoconductive properties that could balance their mechanical limits seem to allow good cranial bone reconstruction. However, these results should be confirmed in the long term and in larger series. Further complicating factors that may affect cranial reconstruction after head injury should be identified in the possible associated alterations of CSF dynamics and in difficulties to manage the traumatic skin lesion and the surgical wound, which also might impact on the cranioplasty outcome. All the abovementioned considerations should be taken into account when dealing with the cranial reconstruction after decompressive craniectomy in children.

Bone response to porous alumina implants coated with bioactive materials, observed using different characterization techniques.

BackgroundImplants or implantable devices should integrate into the host tissue faster than fibrous capsule formation, in which the design of the interface is one of the biggest challenges. Generally, bioactive materials are not viable for load-bearing applications, so inert biomaterials are proposed. However, the surface must be modified through techniques such as coating with bioactive materials, roughness and sized pores. The aim of this research was to validate an approach for the evaluation of the tissue growth on implants of porous alumina coated with bioactive materials.MethodsPorous alumina implants were coated with 45S5 Bioglass® (BG) and hydroxyapatite (HA) and implanted in rat tibiae for a period of 28 days. Ex vivo resections were performed to analyze osseointegration, along with histological analysis, Scanning Electron Microscopy with Energy Dispersive X-Ray spectroscopy (SEM-EDX) line scanning, radiography and biomechanical testing.ResultsGiven that the process of implant integration needs with the bone tissue to be accelerated, it was then seen that BG acted to start the rapid integration, and HA acted to sustaining the process.ConclusionsInert materials coated with bioglass and HA present a potential for application as bone substitutes, preferably with pores of diameters between 100 μm and 400 μm and, restrict for smaller than 100 μm, because it prevents pores without organized tissue formation or vacant. Designed as functional gradient material, stand out for applications in bone tissue under load, where, being the porous surface responsible for the osseointegration and the inner material to bear and to transmit the loads.