Masking the bitter taste of injectable lidocaine HCl formulation for dental procedures.

Several attempts have been made to mask the bitter taste of oral formulations, but none have been made for injectable formulations. This study aims to mask the bitter taste of dental lidocaine HCl (LID) injection using hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and sodium saccharin. Inclusion complexes of LID and HP-ß-CD were prepared by the solution method in 1:1 and 1:2 M ratios. Inclusion complexes in solution were studied using phase solubility in phosphate buffer solutions (pH 8, 9, and 10). Freeze-dried inclusion complexes were characterized using differential scanning calorimetry (DSC), X-ray, Fourier transform infrared (FT-IR), nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), and in vitro release. Injectable formulations were prepared using inclusion complexes and characterized for stability and for taste using an Alpha MOS ASTREE electronic tongue (ETongue). The association constants of HP-ß-CD with lidocaine-free base and its ionized form were found to be 26.23 ± 0.00025 and 0.8694 ± 0.00045 M(-1), respectively. Characterization studies confirmed the formation of stable inclusion complexes of LID and HP-ß-CD. Injectable formulations were found to be stable for up to 6 months at 4°C, 25°C, and 40°C. The taste evaluation study indicated that HP-ß-CD (1:1 and 1:2 M ratios) significantly improved the bitter taste of LID injectable formulation. In conclusion, inclusion complex in the 1:1 M ratio with 0.09% sodium saccharin was considered to be optimum in masking the bitter taste of LID.

Tissue-specific melt electrowritten polymeric scaffolds for coordinated regeneration of soft and hard periodontal tissues.

Periodontitis is a chronic inflammatory condition that often causes serious damage to tooth-supporting tissues. The limited successful outcomes of clinically available approaches underscore the need for therapeutics that cannot only provide structural guidance to cells but can also modulate the local immune response. Here, three-dimensional melt electrowritten (i.e., poly(ε-caprolactone)) scaffolds with tissue-specific attributes were engineered to guide differentiation of human-derived periodontal ligament stem cells (hPDLSCs) and mediate macrophage polarization. The investigated tissue-specific scaffold attributes comprised fiber morphology (aligned vs. random) and highly-ordered architectures with distinct strand spacings (small 250 µm and large 500 µm). Macrophages exhibited an elongated morphology in aligned and highly-ordered scaffolds, while maintaining their round-shape on randomly-oriented fibrous scaffolds. Expressions of periostin and IL-10 were more pronounced on the aligned and highly-ordered scaffolds. While hPDLSCs on the scaffolds with 500 µm strand spacing show higher expression of osteogenic marker (Runx2) over 21 days, cells on randomly-oriented fibrous scaffolds showed upregulation of M1 markers. In an orthotopic mandibular fenestration defect model, findings revealed that the tissue-specific scaffolds (i.e., aligned fibers for periodontal ligament and highly-ordered 500 µm strand spacing fluorinated calcium phosphate [F/CaP]-coated fibers for bone) could enhance the mimicking of regeneration of natural periodontal tissues.

Nanoscale ß-TCP-Laden GelMA/PCL Composite Membrane for Guided Bone Regeneration.

Major advances in the field of periodontal tissue engineering have favored the fabrication of biodegradable membranes with tunable physical and biological properties for guided bone regeneration (GBR). Herein, we engineered innovative nanoscale beta-tricalcium phosphate (ß-TCP)-laden gelatin methacryloyl/polycaprolactone (GelMA/PCL-TCP) photocrosslinkable composite fibrous membranes via electrospinning. Chemo-morphological findings showed that the composite microfibers had a uniform porous network and ß-TCP particles successfully integrated within the fibers. Compared with pure PCL and GelMA/PCL, GelMA/PCL-TCP membranes led to increased cell attachment, proliferation, mineralization, and osteogenic gene expression in alveolar bone-derived mesenchymal stem cells (aBMSCs). Moreover, our GelMA/PCL-TCP membrane was able to promote robust bone regeneration in rat calvarial critical-size defects, showing remarkable osteogenesis compared to PCL and GelMA/PCL groups. Altogether, the GelMA/PCL-TCP composite fibrous membrane promoted osteogenic differentiation of aBMSCs in vitro and pronounced bone formation in vivo. Our data confirmed that the electrospun GelMA/PCL-TCP composite has a strong potential as a promising membrane for guided bone regeneration.

Composite Graded Melt Electrowritten Scaffolds for Regeneration of the Periodontal Ligament-to-Bone Interface.

Periodontitis is a ubiquitous chronic inflammatory, bacteria-triggered oral disease affecting the adult population. If left untreated, periodontitis can lead to severe tissue destruction, eventually resulting in tooth loss. Despite previous efforts in clinically managing the disease, therapeutic strategies are still lacking. Herein, melt electrowriting (MEW) is utilized to develop a compositionally and structurally tailored graded scaffold for regeneration of the periodontal ligament-to-bone interface. The composite scaffolds, consisting of fibers of polycaprolactone (PCL) and fibers of PCL-containing magnesium phosphate (MgP) were fabricated using MEW. To maximize the bond between bone (MgP) and ligament (PCL) regions, we evaluated two different fiber architectures in the interface area. These were a crosshatch pattern at a 0/90° angle and a random pattern. MgP fibrous scaffolds were able to promote in vitro bone formation even in culture media devoid of osteogenic supplements. Mechanical properties after MgP incorporation resulted in an increase of the elastic modulus and yield stress of the scaffolds, and fiber orientation in the interfacial zone affected the interfacial toughness. Composite graded MEW scaffolds enhanced bone fill when they were implanted in an in vivo periodontal fenestration defect model in rats. The presence of an interfacial zone allows coordinated regeneration of multitissues, as indicated by higher expression of bone, ligament, and cementoblastic markers compared to empty defects. Collectively, MEW-fabricated scaffolds having compositionally and structurally tailored zones exhibit a good mimicry of the periodontal complex, with excellent regenerative capacity and great potential as a defect-specific treatment strategy.

Microwave assisted synthesis of amorphous magnesium phosphate nanospheres.

Magnesium phosphate (MgP) materials have been investigated in recent years for tissue engineering applications, attributed to their biocompatibility and biodegradability. This paper describes a novel microwave assisted approach to produce amorphous magnesium phosphate (AMP) in a nanospherical form from an aqueous solution containing Mg(2+) and HPO(4) (2-)/PO(4) (3-). Some synthesis parameters such as pH, Mg/P ratio, solution composition were studied and the mechanism of AMP precursors was also demonstrated. The as-produced AMP nanospheres were characterized and tested in vitro. The results proved these AMP nanospheres can self-assemble into mature MgP materials and support cell proliferation. It is expected such AMP has potential in biomedical applications.

Biomimetic coating of bisphosphonate incorporated CDHA on Ti6Al4V.

Bi-functional coatings of carbonated calcium deficient hydroxyapatite (CDHA) on Ti alloys were developed by using a biomimetic coating process. The bi-functionality was achieved by loading alendonate sodium (AS), an approved bisphosphonate drug used for the treatment of osteoporosis, into the inner layers of CDHA coatings. Three possible methods of loading AS into CDHA coatings were systematically studied and compared. The results indicated that the co-precipitation method had greater benefits and can modify the release profile of AS by incorporating AS in the inner layers of the coatings. As a preliminary study, the influences of applied AS dosage to CDHA coatings were evaluated using XRD and SEM. In vitro tests indicated that the AS content on CDHA coatings played a significant role, and optimum AS content in local area is beneficial for osteoblast cells proliferation. It is expected that the CDHA-AS coatings via the co-precipitation approach have potential for bone tissue engineering applications.

Influence of Fused Deposition Modelling Nozzle Temperature on the Rheology and Mechanical Properties of 3D Printed ß-Tricalcium Phosphate (TCP)/Polylactic Acid (PLA) Composite.

The primary goal of this study is to develop and analyze 3D printed structures based on a well-known composite known as ß-Tricalcium Phosphate (TCP)- polylactic acid (PLA). There are some interesting aspects of this study. First, we developed 3D printable TCP-PLA composite filaments in-house, with high reproducibility, by a one-step process method using a single screw extruder. Second, we explored the physicochemical properties of the developed TCP-PLA composite filaments. Third, we investigated the effect of an FDM-based nozzle temperature of 190 °C, 200 °C, 210 °C, and 220 °C on the composite's crystallinity and rheological and mechanical properties. Results confirmed the successful development of constant-diameter TCP-PLA composite filaments with a homogeneous distribution of TCP particles in the PLA matrix. We observed that a higher nozzle temperature in the FDM process increased the crystallinity of the printed PLA and TCP-PLA structures. As a result, it also helped to enhance the mechanical properties of the printed structures. The rheological studies were performed in the same temperature range used in the actual FDM process, and results showed an improvement in rheological properties at higher nozzle temperatures. The bare polymer and the composite polymer-ceramic melts exhibited lower viscosity and less rigidity at higher nozzle temperatures, which resulted in enhancing the polymer melt flowability and interlayer bonding between the printed layers. Overall, our results confirmed that 3D printable TCP-PLA filaments could be made in-house, and optimization of the nozzle temperature is essential to developing 3D printed composite parts with favorable mechanical properties.

Patient-specific 3D printed Poly-ether-ether-ketone (PEEK) dental implant system.

Fused Filament Fabrication (FFF)-based 3D printing is an efficient technique for developing medical implants, but it is not very useful in developing small yet mechanically robust design-specific fixtures such as dental implants (<15 mm). Specifically, it is challenging to 3D print robust Polyetheretherketone (PEEK) small implants due to PEEK's high melting temperature and melt viscosity. However, in this study, we efficiently utilize high-temperature FFF to develop the first-of-its-kind patient-specific robust PEEK dental implants with high print resolution. Specifically, we explore the effects of critical FFF processing conditions on the mechanical properties of the implants and subsequently determine an optimized set of processing conditions that are essential in developing durable dental implant systems. Our results indicate that the 3D printed dental implants exhibit good fatigue properties and suffice the clinical and industrial requirements for dental implants. Furthermore, we prove that the 3D printed implants exhibit adequate mechanical durability even after simulated (accelerated) aging of 30 years.

Fabrication of novel PLA/CDHA bionanocomposite fibers for tissue engineering applications via electrospinning.

The main theme here is to fabricate PLA (poly lactic-acid)/CDHA (carbonated calcium deficient hydroxyapatite) bionanocomposites, where both the constituents are biocompatible and biodegradable with one dimension in nanometer scale. Such materials are important in tissue engineering applications. The bionanocomposite fibers were fabricated via electrospinning. There are two important signatures of this paper. First, CDHA, rather than HA, is added to PLA as the second phase. As opposed to HA, CDHA mimics the bone mineral composition better and is biodegradable. Therefore, PLA/CDHA fibers should have better biodegradability while maintaining a physiological pH during degradation. To the best of our knowledge, this is the first attempt of electrospinning of such a composite. Second, the CDHA nanoparticles were synthesized using the benign low temperature biomimetic technique, the only route available for the retention of carbonate ions in the HA lattice. The structural properties, degradation behavior, bioactivity, cell adhesion, and growth capability of as-fabricated PLA/CDHA bionanocomposites were investigated. The results show that the incorporation of CDHA decreased PLA fiber diameters, accelerated PLA degradation, buffered pH decrease caused by PLA degradation, improved the bioactivity and biocompatibility of the scaffold. These results prove that PLA/CDHA bionanocomposites have the potential in tissue regeneration applications.

Hydrolysis of monetite/chitosan composites in α-MEM and SBF solutions.

There are two objectives of this work. The first objective is to study the hydrolysis behavior of monetite cements formed in the presence and absence of the chitosan in cell culture media (α-MEM) and simulated body fluid (SBF) solutions at 37°C. During hydrolysis, monetite transformed to carbonated apatite. Therefore, the second objective is to examine how addition of chitosan affects on the formation of carbonated apatite phases. The changes in the phase structure of monetite after hydrolysis reactions were characterized using XRD, FTIR and SEM. Pure monetite and monetite/chitosan composite were soaked in α-MEM and SBF solution for 4 and 7 days. In α-MEM solution, the monetite particles started to transform into carbonated apatite with a slow rate. However, in SBF, the rate of monetite transformation to carbonated apatite was more rapid. The presence of the chitosan had no significant effect on the precipitation of carbonated apatite on the monetite particles.

Fused Filament Fabrication (Three-Dimensional Printing) of Amorphous Magnesium Phosphate/Polylactic Acid Macroporous Biocomposite Scaffolds.

The ultimate goal of this paper is to develop novel ceramic-polymer-based biocomposite orthopedic scaffolds with the help of additive manufacturing. Specifically, we incorporate a bioceramic known as amorphous magnesium phosphate (AMP) into polylactic acid (PLA) with the help of the melt-blending technique. Magnesium phosphate (MgP) was chosen as the bioactive component as previous studies have confirmed its favorable biomaterial properties, especially in orthopedics. Special care was taken to develop constant diameter AMP-PLA composite filaments, which would serve as feedstock for a fused filament fabrication (FFF)-based three-dimensional (3D) printer. Before the filaments were used for FFF, a thorough set of characterization protocols comprising of phase analysis, microstructure evaluations, thermal analysis, rheological analysis, and in vitro degradation determinations was performed on the biocomposites. Scanning electron microscopy (SEM) results confirmed a homogenous dispersion of AMP particles in the PLA matrix. Rheological studies demonstrated good printability behavior of the AMP-PLA filaments. In vitro degradation studies indicated a faster degradation rate in the case of AMP-PLA filaments as compared to the single phase PLA filaments. Subsequently, the filaments were fed into an FFF setup, and tensile bars and design-specific macroporous AMP-PLA scaffolds were printed. The biocomposite exhibited favorable mechanical properties. Furthermore, in vitro cytocompatibility results revealed higher pre-osteoblast cell attachment and proliferation on AMP-PLA scaffolds as compared to single-phase PLA scaffolds. Altogether, this study provides a proof of concept that design-specific bioactive AMP-PLA biocomposite scaffolds fabricated by FFF can be potential candidates as medical implants in orthopedics.

A Highly Ordered, Nanostructured Fluorinated CaP-Coated Melt Electrowritten Scaffold for Periodontal Tissue Regeneration.

Periodontitis is a chronic inflammatory, bacteria-triggered disorder affecting nearly half of American adults. Although some level of tissue regeneration is realized, its low success in complex cases demands superior strategies to amplify regenerative capacity. Herein, highly ordered scaffolds are engineered via Melt ElectroWriting (MEW), and the effects of strand spacing, as well as the presence of a nanostructured fluorinated calcium phosphate (F/CaP) coating on the adhesion/proliferation, and osteogenic differentiation of human-derived periodontal ligament stem cells, are investigated. Upon initial cell-scaffold interaction screening aimed at defining the most suitable design, MEW poly(ε-caprolactone) scaffolds with 500 µm strand spacing are chosen. Following an alkali treatment, scaffolds are immersed in a pre-established solution to allow for coating formation. The presence of a nanostructured F/CaP coating leads to a marked upregulation of osteogenic genes and attenuated bacterial growth. In vivo findings confirm that the F/CaP-coated scaffolds are biocompatible and lead to periodontal regeneration when implanted in a rat mandibular periodontal fenestration defect model. In aggregate, it is considered that this work can contribute to the development of personalized scaffolds capable of enabling tissue-specific differentiation of progenitor cells, and thus guide simultaneous and coordinated regeneration of soft and hard periodontal tissues, while providing antimicrobial protection.

Formation of calcium deficient HAp/collagen composites by hydrolysis of alpha-TCP.

Bone-like composites containing calcium deficient hydroxyapatite (CDHAp) were formed by the hydrolysis of alpha-tricalcium phosphate (alpha-TCP) in the presence of type I collagen. CDHAp-collagen composites were synthesized using two techniques. In one technique alpha-TCP was mixed with non-milled (as-received) collagen prior to the addition of the aqueous solution. In the second, the collagen was milled with alpha-TCP in heptane at room temperature prior to its conversion to CDHAp. The effect of milling strongly facilitates the formation of CDHAp at physiological temperature. The proportion of milled collagen between 5 and 20 wt% present in the alpha-TCP/collagen composites has no significant effect on the rate of CDHAp formation. Variations in pH and in calcium and phosphate concentrations were determined as a function of collagen processing and variations specific to the presence of collagen were discerned. Compared to CDHAp or to composites containing non-milled collagen, diametrical and compressive strengths of CDHAp increased in the presence of milled collagen. Lack of collagen dispersion and incomplete formation of CDHAp during 48 h were the bases for reduced strengths of composites containing non-milled collagen.

Microwave processing of calcium phosphate and magnesium phosphate based orthopedic bioceramics: A state-of-the-art review.

The main theme of this paper is to review microwave-assisted synthesis and processing of calcium and magnesium phosphate bioceramics. Microwave processing of advanced materials has been an active field of research for the last three decades and has been already reviewed in the literature. Microwave processing of bioceramics is being pursued for almost the same period of time. Unfortunately, to the best of our knowledge, we are not aware of any comprehensive review in the literature. Our group has been a significant contributor to the field, and we feel that it is an appropriate time for reviewing the state-of-the-art of the field. The paper is divided into several sections. After rationalizing the motivation behind writing this paper in the introduction, the second section builds on some fundamental aspects of microwave-matter interactions. The third section, representing the synthesis aspects, is subdivided into five sub-sections focusing on various calcium and magnesium phosphates in both crystalline and amorphous forms. The fourth section focuses on magnesium phosphate-based bioceramics. The fifth and the sixth section describe results on the utility of microwave assistance in developing multi-functional coatings on medical implants and orthopedic cements respectively. The subsequent section reviews results on microwave sintering of calcium and magnesium phosphates. The paper concludes with remarks on unresolved issues and future directions of research. It is expected that this comprehensive review on the interdisciplinary topic will further propel the exploration of other novel applications of microwave technology in processing biomaterials by a diverse group of scientists and engineers. STATEMENT OF SIGNIFICANCE: 1. This review highlights the broad-spectrum capabilities of microwave applications in processing orthopedic bioceramics. 2. The article covers "processing" in the broadest sense of the word, comprising of material synthesis, sintering, coating formation, and setting of orthopedic cements. It also expands beyond conventional calcium phosphates to include the emergent family of magnesium phosphates. 3. In vitro/in vivo responses of microwave-processed bioceramics are discussed thus providing an integral understanding of biological aspects of these materials. 4. The comprehensive review on this interdisciplinary topic will help researchers in various disciplines to appreciate the significance and usefulness of microwaves in biomaterials processing. Further, we also believe that it will propel the exploration of other novel applications of microwave technology in the biomaterials sector.

Silver (Ag) doped magnesium phosphate microplatelets as next-generation antibacterial orthopedic biomaterials.

This article reports for the first time our successful result in the synthesis of antibacterial single-phase newberyite (NB, MgHPO4 .3H2 O), an important magnesium phosphate (MgP) bioceramic. The prime novelty lies in the fact that we explore novel MgPs as next-generation orthopedic biomaterials as opposed to conventional calcium phosphates (CaP). While NB has already shown great promise, unlike its competitor struvite (ST, MgNH4 PO4 .6H2 O), NB is not intrinsically antibacterial. Given the havoc created by surgical site infections (SSI) in orthopedics, it would be worthwhile to explore if antibacterial NB can be synthesized cost-effectively. To accomplish that central goal, we used silver ion (Ag+ ) containing precursor solutions and exposed those to microwave irradiation. This action resulted in the rapid synthesis of NB microplatelets. Besides, three other specific objectives are addressed. First, Ag-doping was optimized to preserve the single-phase nature for sustained dopant release. Second, Ag+ release kinetics against common infection causing bacterial strains was analyzed. Finally, we inspected for any harmful effect of Ag-doped NB on MC3T3 preosteoblasts. Interestingly, the single-phase nature of NB microplatelets can be retained until 2 wt % Ag-doping and they exhibit good antibacterial and cytocompatible properties. Even though 3 wt % Ag-doped compositions (composites) were 100% antibacterial; they were cytotoxic.

Extracellular Matrix/Amorphous Magnesium Phosphate Bioink for 3D Bioprinting of Craniomaxillofacial Bone Tissue.

Bioprinting, a promising field in regenerative medicine, holds great potential to create three-dimensional, defect-specific vascularized bones with tremendous opportunities to address unmet craniomaxillofacial reconstructive challenges. A cytocompatible bioink is a critical prerequisite to successfully regenerate functional bone tissue. Synthetic self-assembling peptides have a nanofibrous structure resembling the native extracellular matrix (ECM), making them an excellent bioink component. Amorphous magnesium phosphates (AMPs) have shown greater levels of resorption while maintaining high biocompatibility, osteoinductivity, and low inflammatory response, as compared to their calcium phosphate counterparts. Here, we have established a novel bioink formulation (ECM/AMP) that combines an ECM-based hydrogel containing 2% octapeptide FEFEFKFK and 98% water with AMP particles to realize high cell function with desirable bioprintability. We analyzed the osteogenic differentiation of dental pulp stem cells (DPSCs) encapsulated in the bioink, as well as in vivo bone regeneration, to define the potential of the formulated bioink as a growth factor-free bone-forming strategy. Cell-laden AMP-modified bioprinted constructs showed an improved cell morphology but similar cell viability (∼90%) compared to their AMP-free counterpart. In functional assays, the cell-laden bioprinted constructs modified with AMP exhibited a high level of mineralization and osteogenic gene expression without the use of growth factors, thus suggesting that the presence of AMP-triggered DPSCs' osteogenic differentiation. Cell-free ECM-based bioprinted constructs were implanted in vivo. In comparison with the ECM group, bone volume per total volume for ECM/1.0AMP was approximately 1.7- and 1.4-fold higher at 4 and 8 weeks, respectively. Further, a significant increase in the bone density was observed in ECM/1.0AMP from 4 to 8 weeks. These results demonstrate that the presence of AMP in the bioink significantly increased bone formation, thus showing promise for in situ bioprinting strategies. We foresee significant potential in translating this innovative bioink toward the regeneration of patient-specific bone tissue for regenerative dentistry.

Antibacterial calcium phosphate composite cements reinforced with silver-doped magnesium phosphate (newberyite) micro-platelets.

This article demonstrates our efforts in developing and evaluating all-ceramic, biodegradable composites of calcium phosphate cements (CPCs) reinforced with silver (Ag)-doped magnesium phosphate (MgP) crystals. Two primary goals of this study were to 1) enhance CPC's poor mechanical properties with micro-platelet reinforcement, and 2) impart antibacterial functionalities in composites with the aim to inhibit surgical site infections (SSI). The work embodies three novel features. First, as opposed to well-known reinforcements with whisker or fiber-like morphology, we explored micro-platelets for the first time as the strengthening phase in the CPC matrix. Second, in contrast to conventional polymeric or calcium phosphate (CaP) fibrous reinforcements, newberyite (NB, MgHPO4.3H2O) micro-platelets belonging to the less explored yet promising MgP family, were evaluated as reinforcements for the first time. Third, NB micro-platelets were doped with Ag+ ions (AgNB, Ag content: 2 wt%) for enhancing antibacterial functionalities. Results indicated that 1 wt% of AgNB micro-platelet incorporation in the CPC matrix enhanced the compressive and flexural strengths by 200% and 140% respectively as compared to the un-reinforced ones. Besides, antibacterial assays revealed effective bactericidal functionalities (>99% bacteria kill) of the AgNB reinforced CPCs against Escherichia coli. Finally, cytocompatibility studies confirmed favorable pre-osteoblast cell proliferation and differentiation in vitro. Hence, this effort was successful in developing a self-setting and injectable AgNB reinforced CPC composition with favorable mechanical and antibacterial properties.

Magnetic Calcium Phosphate Cement for Hyperthermia Treatment of Bone Tumors.

This article reports, for the first time, the 'proof-of-concept' results on magnetic monetite (CaHPO4)-based calcium phosphate cements (CPCs) compositions developed for the hyperthermia treatment of bone tumors. Hyperthermia involves the heating of a tumor within a temperature range of 40-45 °C, inducing apoptosis in the tumor cells. This process holds promising potential in the field of cancer treatment and has been proven to be more effective than conventional therapeutics. Hence, we aimed to develop cement compositions that are capable of the hyperthermia treatment of bone tumors. To achieve that central goal, we incorporated iron oxide (Fe3O4), a ferromagnetic material, into monetite and hypothesized that, upon the application of a magnetic field, magnetite will generate heat and ablate the tumor cells near the implantation site. The results confirmed that an optimized content of magnetite incorporation in monetite can generate heat in the range of 40-45 °C upon the application of a magnetic field. Furthermore, the compositions were bioactive and cytocompatible with an osteoblastic cell line.

Bioactive amorphous magnesium phosphate-polyetheretherketone composite filaments for 3D printing.

OBJECTIVE: The aim of this study was to develop bioactive and osseointegrable polyetheretherketone (PEEK)-based composite filaments melt-blended with novel amorphous magnesium phosphate (AMP) particles for 3D printing of dental and orthopedic implants. MATERIALS AND METHODS: A series of materials and biological analyses of AMP-PEEK were performed. Thermal stability, thermogravimetric and differential scanning calorimetry curves of as-synthesized AMP were measured. Complex viscosity, elastic modulus and viscous modulus were determined using a rotational rheometer. In vitro bioactivity was analyzed using SBF immersion method. SEM, EDS and XRD were used to study the apatite-forming ability of the AMP-PEEK filaments. Mouse pre-osteoblasts (MC3T3-E1) were cultured and analyzed for cell viability, proliferation and gene expression. For in vivo analyses, bare PEEK was used as the control and 15AMP-PEEK was chosen based on its in vitro cell-related results. After 4 or 12 weeks, animals were euthanized, and the femurs were collected for micro-computed tomography (µ-CT) and histology. RESULTS: The collected findings confirmed the homogeneous dispersion of AMP particles within the PEEK matrix with no phase degradation. Rheological studies demonstrated that AMP-PEEK composites are good candidates for 3D printing by exhibiting high zero-shear and low infinite-shear viscosities. In vitro results revealed enhanced bioactivity and superior pre-osteoblast cell function in the case of AMP-PEEK composites as compared to bare PEEK. In vivo analyses further corroborated the enhanced osseointegration capacity for AMP-PEEK implants. SIGNIFICANCE: Collectively, the present investigation demonstrated that AMP-PEEK composite filaments can serve as feedstock for 3D printing of orthopedic and dental implants due to enhanced bioactivity and osseointegration capacity.

Highly tunable bioactive fiber-reinforced hydrogel for guided bone regeneration.

One of the most damaging pathologies that affects the health of both soft and hard tissues around the tooth is periodontitis. Clinically, periodontal tissue destruction has been managed by an integrated approach involving elimination of injured tissues followed by regenerative strategies with bone substitutes and/or barrier membranes. Regrettably, a barrier membrane with predictable mechanical integrity and multifunctional therapeutic features has yet to be established. Herein, we report a fiber-reinforced hydrogel with unprecedented tunability in terms of mechanical competence and therapeutic features by integration of highly porous poly(ε-caprolactone) fibrous mesh(es) with well-controlled 3D architecture into bioactive amorphous magnesium phosphate-laden gelatin methacryloyl hydrogels. The presence of amorphous magnesium phosphate and PCL mesh in the hydrogel can control the mechanical properties and improve the osteogenic ability, opening a tremendous opportunity in guided bone regeneration (GBR). Results demonstrate that the presence of PCL meshes fabricated via melt electrowriting can delay hydrogel degradation preventing soft tissue invasion and providing the mechanical barrier to allow time for slower migrating progenitor cells to participate in bone regeneration due to their ability to differentiate into bone-forming cells. Altogether, our approach offers a platform technology for the development of the next-generation of GBR membranes with tunable mechanical and therapeutic properties to amplify bone regeneration in compromised sites. STATEMENT OF SIGNIFICANCE: In this study, we developed a fiber-reinforced hydrogel platform with unprecedented tunability in terms of mechanical competence and therapeutic features for guided bone regeneration. We successfully integrated highly porous poly(ε-caprolactone) [PCL] mesh(es) into amorphous magnesium phosphate-laden hydrogels. The stiffness of the engineered hydrogel was significantly enhanced, and this reinforcing effect could be modulated by altering the number of PCL meshes and tailoring the AMP concentration. Furthermore, the fiber-reinforced hydrogel showed favorable cellular responses, significantly higher rates of mineralization, upregulation of osteogenic-related genes and bone formation. In sum, these fiber-reinforced membranes in combination with therapeutic agent(s) embedded in the hydrogel offer a robust, highly tunable platform to amplify bone regeneration not only in periodontal defects, but also in other craniomaxillofacial sites.