Håkan Engqvist's research while affiliated with Uppsala University and other places

Publications (363)

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Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP formulation (monetite, beta-tricalcium phosphate, and calcium pyrophosphate) guides osteogenesis beyond the physiological envelope. In a sheep model, hollow dome-shaped constructs were plac...
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Interactions between biomolecules and structurally disordered calcium phosphate (CaP) surfaces are crucial for the regulation of bone mineralization by noncollagenous proteins, the organization of complexes of casein and amorphous calcium phosphate (ACP) in milk, as well as for structure-function relationships of hybrid organic/inorganic interfaces...
Article
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Silicon nitride (Si3N4) is a promising biomaterial, currently used in spinal fusion implants. Such implants should result in high vertebral union rates without major complications. However, pseudarthrosis remains an important complication that could lead to a need for implant replacement. Making silicon nitride implants more bioactive could lead to...
Article
Fast and non-invasive pain relief has been one of the primary goals in patient care. One suggested solution is to target the lungs, which allows the drug to be absorbed on a large surface area resulting in a very fast onset reaction. Ceramics possess great properties such as adjustable porosity and mild manufacturing conditions making them good can...
Article
A knowledge on the pullout forces of degradable craniomaxillofacial screws is essential in designing pediatric cranial implants. Herein, four non-identical commercially available screws composed of different aliphatic polyesters were fixated to 3D-printed poly(l-lactide) screw hole test rig and onto a bone substitute material using manual tapping a...
Article
Introduction : The fixation of small intraarticular bone fragments is clinically challenging and an obvious first orthopaedic indication for an effective bone adhesive. In the present study the feasibility of bonding freshly harvested human trabecular bone with OsSticR, a novel phosphoserine modified cement, was evaluated using a bone cylinder mode...
Article
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One major challenge when developing new biomaterials is translating in vitro testing to in vivo models. We have recently shown that a single formulation of a bone tissue adhesive, phosphoserine modified cement (PMC), is safe and resorbable in vivo. Herein, we screened many new adhesive formulations, for cytocompatibility and bioactive ion release,...
Article
The content of crystalline phase plays a significant role in manipulating the microstructure and mechanical properties of glass-ceramics. This study aims at exploring the optimum content of crystalline phase in ZrO2–SiO2 nanocrystalline glass-ceramics (NCGCs) in terms of obtaining the highest mechanical properties. To this end, the mechanical prope...
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The restoration of cranio‐maxillofacial deformities often requires complex reconstructive surgery in a challenging anatomical region, with abnormal soft tissue structures and bony deficits. In this proof‐of‐concept, the possibility of vertical bone augmentation was explored by suspending hemispherically shaped titanium‐reinforced porous calcium pho...
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Precipitation is one of the most common processes to synthesize hydroxyapatite, which is the human body’s mineral forming bone and teeth, and the golden bioceramic material for bone repair. Generally, the washing step is important in the precipitation method to remove the residuals in solution and to stabilize the phase transformation. However, the...
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Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic g...
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Biomaterial development is a long process consisting of multiple stages of design and evaluation within the context of both in vitro and in vivo testing. To streamline this process, mathematical and computational modeling displays potential as a tool for rapid biomaterial characterization, enabling the prediction of optimal physicochemical paramete...
Article
The addition of dopant(s) is an effective strategy to regulate the microstructure and properties of ZrO2-based ceramics. In this study, we investigated the effects of ternary element alloying, namely tantalum (Ta), niobium (Nb), and hafnium (Hf) elements, on the microstructure and transformability of ZrO2 nanocrystallites in a ZrO2-SiO2 nanocrystal...
Article
Effects of dopants with different valences on the densification behavior and phase composition of a ZrO2–SiO2 nanocrystalline glass-ceramic (NCGC) during pressureless sintering were investigated in this study. The raw powder of Ca²⁺, La³⁺, Ce⁴⁺ and Ta⁵⁺ ions doped ZrO2–SiO2 (referred to as Ca-ZS, La-ZS, Ce-ZS, Ta-ZS, respectively) and pure ZrO2–SiO...
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Controlled drug release and targeted drug delivery can reduce systemic toxicity of chemotherapeutics by restricting drugs to the target organ and increasing the local concentration. As tumors and inflamed tissue are often surrounded by an acidic microenvironment, pH-responsive calcium carbonates (CaCO3) are promising vehicles for controlled drug de...
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Osteoporotic fractures are a growing issue due to the increasing incidence of osteoporosis worldwide. High reoperation rates in osteoporotic fractures call for investigation into new methods in improving fixation of osteoporotic bones. In the present study, the strength of a recently developed bone bioadhesive, OsStic tm , was evaluated in vivo usi...
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Objective: The continuing rise of prescription drug abuse has greatly necessitated the development of an abuse-deterrent formulation. Geopolymers are a promising base for drug design as they allow for tuneable drug release and possess superior physical and chemical properties compared with conventional pharmaceutical excipients.Methods: Geopolymer...
Article
Silk fibroin (SF) hydrogels have attracted extensive interest in biomedical applications due to their biocompatibility and wide availability. However, their generally poor mechanical properties limit their utility. Here, injectable, ready-to-use SF-based composites, simultaneously induced and reinforced by acidic calcium phosphates, were prepared v...
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The golden standard to treat acute pain is by intravenous drug delivery of opioids such as fentanyl or morphine. Intravenous drug delivery requires the placement of an intravenous (IV) port, which can cause infections, dislodgments, and distress to the patients, and therefore a non-invasive method is desirable. Pulmonary drug delivery is a non-inva...
Article
It is challenging to develop a material that combines good mechanical properties and high translucency since these properties are generally not coincident in one material. In this study, we prepared ZrO2-SiO2 nanocrystalline glass-ceramics that combines the above two types of properties. Raw powder with 55 mol%, 65 mol%, and 75 mol% ZrO2 and each w...
Article
Zirconia-based ceramics are becoming a popular biomaterial in dental implantology due to their natural silver-white color, excellent mechanical properties, and good biocompatibility. However, zirconia-based ceramics are biologically inert, which limits their ability to integrate with the surrounding human tissues. To solve this problem, the bioacti...
Article
Thermal stability of nanocrystallites plays an important role in the manufacturing and application of nanocrystalline ceramics/glass-ceramics. This study explores the effects of thermal treatments on the microstructures of two ZrO2-SiO2 nanocrystalline glass-ceramics (NCGCs), an undoped one and a yttria-doped one. The two as-sintered NCGCs were com...
Chapter
Calcium phosphate cements (CPCs) are commonly used as bone void fillers and to reinforce hardware in fracture repair. They are injectable, mouldable and self-setting in vivo, and in addition to being osteoconductive they can also be both bioactive and resorbable, which makes them interesting as bone regenerative biomaterials. The cement sets throug...
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In a 52-week ovine calvaria implantation model, the restoration of cranial defects with a bare titanium mesh (Ti-mesh) and a titanium mesh embedded in a calcium phosphate (CaP-Ti) were evaluated in seven animals. During the study, no major clinical abnormalities were observed, and all sheep presented a normal neurologic assessment. Blood and CSF an...
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This study aimed to evaluate the occluding/remineralization performance and resistance to acid attacks of the mineralization layer formed by a tooth-desensitizing gel containing amorphous calcium magnesium phosphate (ACMP) particles and compare it to six other desensitizing products available on the market. Similar comprehensive studies are few and...
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The use of calcium phosphates (CaPs) as synthetic bone substitutes should ideally result in a volumetric balance with concomitant bone formation and degradation. Clinical data on such properties is nevertheless lacking, especially for monetite-based CaPs. However, a monetite-based composite implant has recently shown promising cranial reconstructio...
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Existing methods for testing prosthetic implants suffer from critical limitations, creating an urgent need for new strategies that facilitate research and development of implants with enhanced osseointegration potential. Herein, we describe a novel, biomimetic, human bone platform for advanced testing of implants in vitro, and demonstrate the scien...
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There is a gap between injectable and scaffold-like bioceramics. Injectable bioactive materials, such as bone cement and hydrogel, are good for minimized surgery, but the extremely low porosity and small pore size limited enhanced bone repair and regeneration. Macroporous bioceramic scaffolds are used because of the controlled pore size and porosit...
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Significance Large cranial reconstructions are increasingly performed worldwide and still represent a substantial clinical challenge. The gold standard, autologous bone, has limited availability and high donor-site morbidity. Current alloplastic materials are associated with high complication and failure rates. This study shows the capacity of a cu...
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A patient-specific titanium-reinforced calcium phosphate (CaP–Ti) cranial implant has recently shown promising clinical results. Currently, its mesh-type titanium structure is additively manufactured using laser beam powder bed fusion (L-PBF). Nevertheless, an electron-beam (E-PBF) process could potentially be more time efficient. This study aimed...
Article
From a multitude of homonuclear and heteronuclear correlation magic-angle-spinning (MAS) NMR experiments, we present thorough structural and phase-quantification analyses of calcium phosphate cements (CPCs) that incorporate either L-Serine (Ser) or O-Phospho-L-Serine (Pser), thereby rendering the cements strongly bone-adhesive and suitable for biom...
Article
Dentin hypersensitivity can be reduced by the use of a remineralization agent to hinder movement of fluids within the dentin tubules. Penetration of particles into the tubules and a continuous release of Ca²⁺ and phosphate ions can induce the mineralization of a material mimicking the mineral component of dentin, sealing the tubules. In this work,...
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Ceramic coatings may prolong the lifetime of joint implants. Certain ions and wear debris may however lead to negative biological effects. SiN-based materials may substantially reduce these effects, but still need optimization for the application. In this study, a combinatorial deposition method enabled an efficient evaluation of a range of Si–Fe–C...
Article
Occlusion of exposed dentin tubules may eliminate or reduce dentin hypersensitivity by hindering fluid movements within the tubules. In this study, the mode of action of spherical particles of amorphous calcium magnesium phosphate (180-440 nm in diameter) was studied. A degradation study of the particles in Tris-HCl buffer showed that the particles...
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Ceramic coatings deposited on orthopedic implants are an alternative to achieve and maintain high wear resistance of the metallic device, and simultaneously allow for a reduction in metal ion release. Silicon nitride based (SiNx) coatings deposited by high power impulse magnetron sputtering (HiPIMS) have shown potential for use in joint replacement...
Article
Dopant segregation at grain boundaries (GBs) in ceramics has been widely reported, while whether similar segregation behavior occurs in glass‐ceramics remains unknown. The distribution of dopant in glass‐ceramics may be totally different due to the existence of glass phase. This study examines the distribution of Y3+ ions in a ZrO2‐SiO2 glass‐ceram...
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Polydimethylsiloxane (PDMS) is among the most widely used materials for organ-on-chip systems. Despite its multiple beneficial characteristics from an engineering point of view, there is a concern about the effect of PDMS on the cells cultured in such devices. The aim of this study was to enhance the understanding of the effect of PDMS on cellular...
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Phosphoserine-modified cements (PMCs) are a family of wet-field tissue adhesives that bond strongly to bone and biomaterials. The present study evaluated variations in the adhesive strength using a scatter plot, failure mode, and a regression analysis of eleven factors. All single-factor, continuous-variable correlations were poor (R2 < 0.25). The...
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In this review, we first briefly introduce the general knowledge of glass-ceramics, including the discovery and development, the application, the microstructure, and the manufacturing of glass-ceramics. Second, the review presents a detailed description of glass-ceramics in dentistry. In this part, the history, property requirements, and manufactur...
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In this paper we report the synthesis of a library of phospho-amino acid analogues, via a novel single-step allyl-phosphoester protection/Pd-mediated deprotection strategy. These phosphoserine and phosphotyrosine analogues were then applied as additives to create adhesive calcium phosphate cements, allowing us to probe the chemical origins of the i...
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A new class of materials, bone adhesives, could revolutionise the treatment of highly fragmented fractures. We present the first biological safety investigation of a bio-inspired bone adhesive. The formulation was based upon a modified calcium phosphate cement that included the amino acid phosphoserine. This material has recently been described as...
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Cranial implants are used to repair bone defects following neurosurgery or trauma. At present, there is a lack of data on their mechanical response, particularly in impact loading. The aim of the present study was to assess the mechanical response of a recently developed composite calcium phosphate–titanium (CaP–Ti) implant at quasi-static and impa...
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Titanium (Ti) implants are commonly regarded as well accepted by the body. However, metal ion release is still a cause for concern. A small decrease in pH, which can be caused by inflammation, may produce a large increase in the corrosion rate of Ti implants. Coating the alloy with a buffer layer could have a significant protective effect. In this...
Article
We present a comprehensive composition analysis of calcium phosphate cements (CPCs) incorporating increasing amounts of bioactive pyrophosphate species (up to 17 wt% P2O7). These cements comprise primarily poorly ordered monetite (CaHPO4) or brushite (CaHPO4⋅2H2O) and are investigated for enhanced osteoinductive bone/tooth implants. The specimens w...
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We present a solid-state nuclear magnetic resonance (NMR) spectroscopy study of the local 31 P and 1 H environments in monetite [CaHPO 4 ; dicalcium phosphate anhydrous (DCPA)], as well as their relative spatial proximities. Each of the three 1 H NMR peaks was unambiguously assigned to its respective crystallographically unique H site of monetite,...
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Peri-implantitis, a disease caused by bacteria, affects dental implants in patients. It is widely treated with antibiotics, however, with growing antibiotic resistance new strategies are required. Titanium-copper alloys are prospective antibacterial biomaterials, with the potential to be a remedy against peri-implantitis and antibiotic resistance....
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In the oral cavity, dental implants—most often made of commercially pure titanium—come in contact with bacteria, and antibacterial management has been researched extensively to improve patient care. With antibiotic resistance becoming increasingly prevalent, this has resulted in copper being investigated as an antibacterial element in alloys. In th...
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Alloying copper into pure titanium has recently allowed the development of antibacterial alloys. The alloying of biocompatible elements (Nb, Ta and Zr) into pure titanium has also achieved higher strengths for a new alloy of Ti-1.6 wt.% Nb-10 wt.% Ta-1.7 wt.% Zr (TNTZ), where strength was closer to Ti-6Al-4V and higher than grade 4 titanium. In the...
Preprint
We report the synthesis of a library of phospho-amino acid analogues using a novel allyl-phosphoester deprotection strategy. By reacting phenols and alcohols with a combination of POCl3 and allyl alcohol we generate protected phosphoesters that can be subsequently deprotected via treatment with Pd(OAc)2. We go on to show that the generated phosphos...
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Ceramic coatings may be applied onto metallic components of joint replacements for improved wear and corrosion resistance as well as enhanced biocompatibility, especially for metal-sensitive patients. Silicon nitride (SiNx) coatings have recently been developed for this purpose. To achieve a high coating density, necessary to secure a long-term per...
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The development of new biomaterials and drug delivery systems necessitates animal experimentation to demonstrate biocompatibility and therapeutic efficacy. Reduction and replacement of the requirement to conduct experiment using full-grown animals has been achieved through utilising zebrafish embryos, a promising bridge model between in vitro and i...
Article
An approximately 1-µm thick hydroxyapatite coating was biomimetically deposited on an alkali-treated, commercially available orthopedic screw surface (type II anodized titanium). Tobramycin loaded into the coating via a simple soaking method was shown to provide a sustained release above the minimal inhibitory concentration 0.2 µg/µl for up to two...
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