Synthesis and Characterizations of Bioactive Glass Nanoparticle-Incorporated Triblock Copolymeric Injectable Hydrogel for Bone Tissue Engineering.

Recently, injectable hydrogels have attracted much interest in tissue engineering (TE) applications because of their controlled flowability, adaptability, and easy handling properties. This work emphasizes the synthesis and characterizations of bioactive glass (BAG) nanoparticle-reinforced poly(ethylene glycol) (PEG)- and poly(N-vinylcarbazole) (pNVC)-based minimally invasive composite injectable hydrogel suitable for bone regeneration. First, the copolymer was synthesized from a combination of PEG and pNVC through reversible addition-fragmentation chain-transfer (RAFT) polymerization and nanocomposite hydrogel constructs were subsequently prepared by conjugating BAG particles at varying loading concentrations. Gel permeation chromatography (GPC) analysis confirmed the controlled nature of the polymer. Various physicochemical characterization results confirmed the successful synthesis of copolymer and nanocomposite hydrogels that showed good gelling and injectability properties. Our optimal nanocomposite hydrogel formulation showed excellent swelling properties in comparison to the copolymeric hydrogel due to the presence of hydrophilic BAG particles. The bone cell proliferation rate was found to be evidently higher in the nanocomposite hydrogel than in the copolymeric hydrogel. Moreover, the enhanced level of ALP activity and apatite mineralization for the nanocomposite in comparison to that for the copolymeric hydrogel indicates accelerated in vitro osteogenesis. Overall, our study findings indicate BAG particle-conjugated nanocomposite hydrogels can be used as promising grafting materials in orthopedic reconstructive surgeries complementary to conventional bone graft substitutes in cancellous bone defects due to their 3D porous framework, minimal invasiveness, and ability to form any desired shape to match irregular bone defects.

Bioactive glasses incorporating less-common ions to improve biological and physical properties.

Bioactive glasses (BGs) have been a focus of research for over five decades for several biomedical applications. Although their use in bone substitution and bone tissue regeneration has gained important attention, recent developments have also seen the expansion of BG applications to the field of soft tissue engineering. Hard and soft tissue repair therapies can benefit from the biological activity of metallic ions released from BGs. These metallic ions are incorporated in the BG network not only for their biological therapeutic effects but also in many cases for influencing the structure and processability of the glass and to impart extra functional properties. The "classical" elements in silicate BG compositions are silicon (Si), phosphorous (P), calcium (Ca), sodium (Na), and potassium (K). In addition, other well-recognized biologically active ions have been incorporated in BGs to provide osteogenic, angiogenic, anti-inflammatory, and antibacterial effects such as zinc (Zn), magnesium (Mg), silver (Ag), strontium (Sr), gallium (Ga), fluorine (F), iron (Fe), cobalt (Co), boron (B), lithium (Li), titanium (Ti), and copper (Cu). More recently, rare earth and other elements considered less common or, some of them, even "exotic" for biomedical applications, have found room as doping elements in BGs to enhance their biological and physical properties. For example, barium (Ba), bismuth (Bi), chlorine (Cl), chromium (Cr), dysprosium (Dy), europium (Eu), gadolinium (Gd), ytterbium (Yb), thulium (Tm), germanium (Ge), gold (Au), holmium (Ho), iodine (I), lanthanum (La), manganese (Mn), molybdenum (Mo), nickel (Ni), niobium (Nb), nitrogen (N), palladium (Pd), rubidium (Rb), samarium (Sm), selenium (Se), tantalum (Ta), tellurium (Te), terbium (Tb), erbium (Er), tin (Sn), tungsten (W), vanadium (V), yttrium (Y) as well as zirconium (Zr) have been included in BGs. These ions have been found to be particularly interesting for enhancing the biological performance of doped BGs in novel compositions for tissue repair (both hard and soft tissue) and for providing, in some cases, extra functionalities to the BG, for example fluorescence, luminescence, radiation shielding, anti-inflammatory, and antibacterial properties. This review summarizes the influence of incorporating such less-common elements in BGs with focus on tissue engineering applications, usually exploiting the bioactivity of the BG in combination with other functional properties imparted by the presence of the added elements.

Research progress on the biological modifications of implant materials in 3D printed intervertebral fusion cages.

Anterior spine decompression and reconstruction with bone grafts and fusion is a routine spinal surgery. The intervertebral fusion cage can maintain intervertebral height and provide a bone graft window. Titanium fusion cages are the most widely used metal material in spinal clinical applications. However, there is a certain incidence of complications in clinical follow-ups, such as pseudoarticulation formation and implant displacement due to nonfusion of bone grafts in the cage. With the deepening research on metal materials, the properties of these materials have been developed from being biologically inert to having biological activity and biological functionalization, promoting adhesion, cell differentiation, and bone fusion. In addition, 3D printing, thin-film, active biological material, and 4D bioprinting technology are also being used in the biofunctionalization and intelligent advanced manufacturing processes of implant devices in the spine. This review focuses on the biofunctionalization of implant materials in 3D printed intervertebral fusion cages. The surface modifications of implant materials in metal endoscopy, material biocompatibility, and bioactive functionalizationare summarized. Furthermore, the prospects and challenges of the biofunctionalization of implant materials in spinal surgery are discussed. Fig.a.b.c.d.e.f.g As a pre-selected image for the cover, I really look forward to being selected. Special thanks to you for your comments.

Evaluation of Ti/Al alloy coated with biogenic hydroxyapatite as an implant device in dogs' femur bones.

The main target of the present research was a full assessment of the toxicity effects and biocompatibility of a Ti/Al-alloy device coated with biogenic hydroxyapatite (bHA) when implanted in dogs in comparison with those of an uncoated Ti/Al-alloy device. The coating of the alloy was carried out using controlled high-velocity suspension flame spray (HVSFS) technique. Both coated and uncoated devices were implanted in dogs' femur bones for different time periods (45 days and 90 days). Bone-formation ability and healing were followed up, and blood analysis was performed, at Time zero (immediately post surgery), and then at 3 days, 45 days, and 90 days post surgery. Bone mineral density checks, radiological scans of the femur bone, and histological analysis were also conducted. The in-vivo study results proved that implantation of a device made from bHA-coated Ti/Al alloy in dogs' femur bones is completely safe. This is due to the high osteoconductivity of the coated alloy, which enables the formation of new bone and a full connection between new and original bone material. At 90 days post surgery, the coated alloy had been completely digested within the original bone; thus, it appeared as a part of the femur bone and not as a foreign body. Both the scanning electron microscopy with energy-dispersive X-ray and histology analysis findings affirmed the results. Furthermore, the blood tests indicated no toxicity effects during the 90 days of implantation.

PGS/HAp Microporous Composite Scaffold Obtained in the TIPS-TCL-SL Method: An Innovation for Bone Tissue Engineering.

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (1H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1ß, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.

Synthesis of silver nanoparticle-decorated hydroxyapatite nanocomposite with combined bioactivity and antibacterial properties.

Combination of bioactive material such as hydroxyapatite (HAp) with antibacterial agents would have great potential to be used as bone implant materials to avert possible bacterial infection that can lead to implant-associated diseases. The present study aimed to develop an antibacterial silver nanoparticle-decorated hydroxyapatite (HAp/AgNPs) nanocomposite using chemical reduction and thermal calcination approaches. In this work, natural HAp that was extracted from chicken bone wastes is used as support matrix for the deposition of silver nanoparticles (AgNPs) to produce HAp/AgNPs nanocomposite. XRD, FESEM-EDX, HRTEM, and XPS analyses confirmed that spherical AgNPs were successfully synthesized and deposited on the surface of HAp particles, and the amount of AgNPs adhered on the HAp surface increased with increasing AgNO3 concentration used. The synthesized HAp/AgNPs nanocomposites demonstrated strong antibacterial activity against Staphylococcus aureus bacteria, where the antibacterial efficiency is relied on the amount and size of deposited AgNPs. In addition, the in vitro bioactivity examination in Hank's balanced salt solution showed that more apatite were grown on the surface of HAp/AgNPs nanocomposite when AgNO3 concentration used >1 wt.%. Such nanocomposite with enhanced bioactivity and antibacterial properties emerged as a promising biomaterial to be applied for dentistry and orthopedic implantology.

Biological evaluation of the modified nano-amorphous phosphate calcium doped with citrate/poly-amino acid composite as a potential candidate for bone repair and reconstruction.

Large numbers of research works related to fabricating organic-inorganic composite materials have been carried out to mimic the natural structure of bone. In this study, a new modified n-ACP doped with citrate (n-ACP-cit)/poly (amino acids) (PAA) composite (n-ACP-cit/PAA) was synthesized by employing high bioactive n-ACP-cit and the biodegradable and biocompatible PAA copolymer. Its basic structure was characterized by X-ray diffraction spectroscopy, Fourier transformed infrared spectroscopy, and X-ray photoelectron spectroscopy. Moreover, the degradability, bioactivity, biocompatibility, and osteoconductivity of n-ACP-cit/PAA composite were evaluated in vitro and in vivo, using simulated body fluid (SBF) solution soaking test, mouse bone marrow mesenchymal stem cells proliferation and differentiation, morphological observation test, expression of genes associated with osteogenesis, and bone defect model repair test, respectively. The modified n-ACP-cit/PAA composite exhibited a much higher weight loss rate (36.01 wt.%) than that of PAA (23.99 wt.%) after immersing in SBF solution for 16 weeks and the pH values of local environment restored to neutral condition. Moreover, cells co-culturing with composites exhibited higher alkaline phosphatase activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes (Bmp-2, Colla I, OCN, OPN, and Runx-2) than that of PAA. Furthermore, the bone defect model repair test revealed that the composite could be intimately incorporated with the surrounding bone without causing any deleterious reaction and capable of guiding new bone formation. Together, these results indicated that the new modified bone repair n-ACP-cit/PAA composite material with specific characteristics may be designed for meeting diverse requirements from biomedical applications.

The effect of synthetic bone graft substitutes on bone formation in rabbit calvarial defects.

The aim of this study was to evaluate the influence of the intensity of the biomimetic hydroxyapatite (HA) coating of α-tricalcium phosphate (α-TCP) on biomaterial degradation and bone formation. Twenty-four female NZW rabbits of approximately 12 weeks of age were used. Critical size defects were randomly treated with 3%:97% HA:α-TCP (BBCP1), 12%:88% HA:α-TCP (BBCP2), and 23%:77% HA:α-TCP (BBCP3), respectively or sham. All defects were covered with a resorbable collagen membrane. Animals were euthanized after 3 and 12 weeks of healing and samples were investigated by micro-CT and histologic analysis. Ingrowth of newly formed woven bone from the original bone at 3-week healing period was observed in all samples. At the 12-week healing period, the new bone in the peripheral area was mainly lamellar and in the central region composed of both woven and lamellar bone. New bony tissue was found on the surface of all three types of granules and at the interior of the BBCP1 granules. Samples with 3% HA showed significantly less residual biomaterial in comparison to the other two groups. Furthermore, BBCP1 significantly promoted new bone area as compared to other three groups and more bone volume as compared to the control. Within its limitations, this study indicated the highest degradation rate in case of BBCP1 concomitant with the highest rate of bone formation. Hence, formation of new bone can be affected by the level of biomimetic HA coating of α-TCP.

Nanocomposite Clay-Based Bioinks for Skeletal Tissue Engineering.

Biofabrication is revolutionizing substitute tissue manufacturing. Skeletal stem cells (SSCs) can be blended with hydrogel biomaterials and printed to form three-dimensional structures that can closely mimic tissues of interest. Our bioink formulation takes into account the potential for cell printing including a bioink nanocomposite that contains low fraction polymeric content to facilitate cell encapsulation and survival, while preserving hydrogel integrity and mechanical properties following extrusion. Clay inclusion to the nanocomposite strengthens the alginate-methylcellulose network providing a biopaste with unique shear-thinning properties that can be easily prepared under sterile conditions. SSCs can be mixed with the clay-based paste, and the resulting bioink can be printed in 3D structures ready for implantation. In this chapter, we provide the methodology for preparation, encapsulation, and printing of SSCs in a unique clay-based bioink.

Structural and chemical features of xenograft bone substitutes: A systematic review of in vitro studies.

Xenograft bone substitutes are obtained from different species and prepared by various procedures including heat treatment, hydrazine, and chemical and hydrothermal methods. These grafts are utilized widely because of similar structure and properties to human bone, proper bone formation, and biocompatibility. The aim of this systematic review was to evaluate different xenografts from structural and chemical aspects. In vitro studies published in English language, which assessed xenografts' features, met the inclusion criteria. Electronic search of four databases including PubMed, Google Scholar, Scopus, and Web of Science and a hand search until September 2020 were performed. The irrelevant studies were the ones which focused on cell adhesion and effect of growth factors. Finally, 25 studies were included in the review. Nineteen studies used bovine xenografts, and 12 studies applied heat treatment as their preparation method. Particles showed various morphologies, and their largest size was observed at 5 mm. From 18 studies, it is found that the smallest pore size was 1.3 µm and the highest pore size was 1000 µm. There is large heterogeneity of porosity, crystallinity, Ca/P ratio, and osteogenesis based on the preparation method. Proper porosity and the connection between pores affect bone regeneration. Therefore, biomaterial selection and outcomes evaluation should be interpreted separately.

Preparation and characterization of a novel polylactic acid/hydroxyapatite composite scaffold with biomimetic micro-nanofibrous porous structure.

Combining synthetic polymer scaffolds with inorganic bioactive factors is widely used to promote the bioactivity and bone conductivity of bone tissue. However, except for the chemical composition of scaffold, the biomimetic structure also plays an important role in its application. In this study, we report the fabrication of polylactic acid/hydroxyapatite (PLA/HA) composite nanofibrous scaffolds via phase separation method to mimic the native extracellular matrix (ECM). The SEM analysis showed that the addition of HA dramatically impacted the morphology of the PLA matrix, which changed from 3D nanofibrous network structure to a disorderly micro-nanofibrous porous structure. At the same time, HA particles could be evenly dispersed at the end of the fiber. The FTIR and XRD demonstrated that there was not any chemical interaction between PLA and HA. Thermal analyses showed that HA could decrease the crystallization of PLA, but improve the thermal decomposition temperature of the composite scaffold. Moreover, water contact angle analysis of the PLA/HA composite scaffold demonstrated that the hydrophilicity increased with the addition of HA. Furthermore, apatite-formation ability tests confirmed that HA could not only more and faster induced the deposition of weak hydroxyapatite but also induced specific morphology of HA.

Effective production of multifunctional magnetic-sensitive biomaterial by an extrusion-based additive manufacturing technique.

A calcium phosphate (CaP)-based scaffold used as synthetic bone grafts, which smartly combines precise dimensions, controlled porosity and therapeutic functions, presents benefits beyond those offered by conventional practices, although its fabrication is still a challenge. The sintering step normally required to improve the strength of the ceramic scaffolds precludes the addition of any biomolecules or functional particles before this stage. This study presents a proof of concept of multifunctional CaP-based scaffolds, fabricated by additive manufacturing from an innovative ink composition, with potential for bone regeneration, cancer treatment by local magnetic hyperthermia and drug delivery platforms. Highly loaded inks comprising iron-doped hydroxyapatite and ß-tricalcium phosphate powders suspended in a chitosan-based solution, in the presence of levofloxacin (LEV) as model drug and magnetic nanoparticles (MNP), were developed. The sintering step was removed from the production process, and the integrity of the printed scaffolds was assured by the polymerization capacity of the ink composite, using genipin as a crosslinking agent. The effects of MNP and LEV on the inks' rheological properties, as well as on the mechanical and structural behaviour of non-doped and iron-doped scaffolds, were evaluated. Magnetic and magneto-thermal response, drug delivery and biological performance, such as cell proliferation in the absence and presence of an applied magnetic field, were also assessed. The addition of a constant amount of MNP in the iron-doped and non-doped CaP-based inks enhances their magnetic response and induction heating, with these effects more pronounced for the iron-doped CaP-based ink. These results suggest a synergistic effect between the iron-doped CaP-based powders and the MNP due to ferro/ferrimagnetic interactions. Furthermore, the iron presence enhances human mesenchymal stem cell metabolic activity and proliferation.

Comparative study of photoinitiators for the synthesis and 3D printing of a light-curable, degradable polymer for custom-fit hard tissue implants.

Three-dimensional (3D) printing enhances the production of on-demand fabrication of patient-specific devices, as well as anatomically fitting implants with high complexity in a cost-effective manner. Additive systems that employ vat photopolymerisation such as stereolithography (SLA) and digital light projection are used widely in the field of biomedical science and engineering. However, additive manufacturing methods can be limited by the types of materials that can be used. In this study, we present an isosorbide-based formulation for a polymer resin yielding a range of elastic moduli between 1.7 and 3 GN mm-2 dependent on the photoinitiator system used as well as the amount of calcium phosphate filler added. The monomer was prepared and enhanced for 3D-printing using an SLA technique that delivered stable and optimized 3D-printed models. The resin discussed could potentially be used following major surgery for the correction of congenital defects, the removal of oral tumours and the reconstruction of the head and neck region. The surgeon is usually limited with devices available to restore both function and appearance and with the ever-increasing demand for low-priced and efficient facial implants, there is an urgent need to advance new manufacturing approaches and implants with a higher osseointegration performance.

An innovative strategy to treat large metaphyseal segmental femoral bone defect using customized design and 3D printed micro-porous prosthesis: a prospective clinical study.

Five patients with segmental irregular-shaped bone defect of the femur were recruited in this study from 2017.12 to 2018.11. All patients were treated by customized design and 3D printed micro-porous prosthesis. And the procedure was divided into stages: radical debridement and temporary fixation (the first stage); the membrane formation and virtual surgery (intervening period for 6-8 weeks); definite reconstruction the defects (the second stage). Routine clinical follow-up and radiographic evaluation were done to assess bone incorporation and complications of internal fixation. The weight-bearing time and the joint function of the patients were recorded. The patients were followed up for an average of 16.4 months. The average length of bone defect and the distal residual bone was 12 cm and 6.5 cm. The average time of partial weight-bearing and full weight-bearing was 12.7 days and 2.6 months. X-ray demonstrated good osseous integration of the implant/bone interface. No complications occurred such as implant loosening, subsidence, loss of correction and infection. At the last follow-up, Harris score of hip joint was excellent in 2 cases, good in 2 cases, fair in 1 case; HSS score of knee joint was good in 4 cases, middle in 1 case. From our study, we concluded that meticulous customized design 3D printed micro-porous prosthesis combined with intramedullary nail may be a promising and an alternative strategy to treat metaphyseal segmental irregular-shaped femoral bone defect, especially for cases with massive juxta-articular bone loss.

Rotary-jet spun polycaprolactone/nano-hydroxyapatite scaffolds modified by simulated body fluid influenced the flexural mode of the neoformed bone.

Polycaprolactone (PCL) is a biocompatible, biodegradable synthetic polymer which in combination with nanohydroxyapatite (nHAp) can give rise to a low cost, nontoxic bioactive product with excellent mechanical properties and slow degradation. Here we produced, characterized and evaluated in vivo the bone formation of PCL/nHAp scaffolds produced by the rotary jet spinning technique. The scaffolds produced were firstly soaked into simulated body fluid for 21 days to also obtain nHAp onto PCL/nHAp scaffolds. Afterwards, the scaffolds were characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy and Raman spectroscopy. For in vivo experiments, 20 male Wistar rats were used and randomly divided in 4 experimental groups (n = 5). A critical defect of 3 mm in diameter was made in the tibia of the animals, which were filled with G1 control (clot); G2-PCL scaffold; G3-PCL/nHAp (5%) scaffold; G4-PCL/nHAp (20%) scaffold. All animals were euthanized 60 days after surgery, and the bone repair in the right tibiae were evaluated by radiographic analysis, histological analysis and histomorphometric analysis. While in the left tibias, the areas of bone repair were submitted to the flexural strength test. Radiographic and histomorphometric analyses no showed statistical difference in new bone formation between the groups, but in the three-point flexural tests, the PCL/nHAp (20%) scaffold positively influenced the flexural mode of the neoformed bone. These findings indicate that PCL/nHAp (20%) scaffold improve biomechanical properties of neoformed bone and could be used for bone medicine regenerative.

In-vitro bioactivity of silicate-phosphate glasses using agriculture biomass silica.

In the present work, silica extracted from the agricultural waste material; rice husk (RH) was utilized for the synthesis of biocompatible glass of general composition SiO2-P2O5-CaO-MgO-MoO3. In the synthesized glasses P2O5 (5%) and CaO (25%) was kept constant whereas MgO and MoO3 was varied from 10% to 20% and 0% to 5% respectively. The structural, morphological, elemental and functional properties of silica as well as the derived glasses were analyzed by X-Ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Energy Dispersive X-ray spectroscopy (EDX) and Fourier Transform Infrared (FTIR) spectroscopy techniques. The effect of MoO3 on the structural and thermal properties of silicate phosphate glasses has been studied in details. The bioactivity of as-synthesized glass samples were further evaluated after immersion in Simulated Body Fluid (SBF) solution which shows bioactive properties thus enabling them to be used as scaffolds in implant materials.

Effects of hydroxyapatite on PMMA-HAp cement for biomedical applications.

OBJECTIVE: The main goal of this study was to examine the influence of hydroxyapatite (HAp) macroaggreate concentrations on thermal and mechanical properties of radioactive bone cement and to study the relation of glass transition Tg with its mechanical properties. METHODS: The bone cement as (1-x)PMMA-xHAp binary system was prepared in six [x] distinct concentration parameters of 0.0 up to 0.5. The HAp was synthesized using a solgel procedure following calcination by thermal treatment. The composite was prepared in cold based (non-radioactive) mixing polymethyl methacrylate (PMMA) and HAp. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and mechanical compressive strength (CS) were used to measure the thermal and mechanical properties. RESULTS: The DSC and TGA thermal profiles in function to concentration parameter [x] were presented. The CS lies in a range of 3.71-7.37 MPa and the glass transition temperature Tg = 126.27 °C. There was a direct relationship between the PMMA-HAp thermoplastic properties with mechanical and thermal properties in function of HAp concentrations. CONCLUSION: The specific PMMA-HAp composite, with a concentration ratio of 1:1 and HAp thermal treatment at the Tg, provides a material with a compression strength of 7.37 MPa and a suitable amount of porous similar to a trabecular bone, possible to apply in bone cement implants, regardless of whether they are radioactive or not.

Novel Extrusion-Microdrilling Approach to Fabricate Calcium Phosphate-Based Bioceramic Scaffolds Enabling Fast Bone Regeneration.

This study proposes a novel approach, termed extrusion-microdrilling, to fabricate three-dimensional (3D) interconnected bioceramic scaffolds with channel-like macropores for bone regeneration. The extrusion-microdrilling method is characterized by ease of use, high efficiency, structural flexibility, and precision. The 3D interconnected ß-tricalcium phosphate bioceramic (EM-TCP) scaffolds prepared by this method showed channel-like square macropores (∼650 µm) by extrusion and channel-like round macropores (∼570 µm) by microdrilling as well as copious micropores. By incorporating a strontium-containing phosphate-based glass (SrPG), the obtained calcium phosphate-based bioceramic (EM-TCP/SrPG) scaffolds had noticeably higher compressive strength, lower porosity, and smaller macropore size, tremendously enhanced in vitro proliferation and osteogenic differentiation of mouse bone marrow stromal cells, and suppressed in vitro osteoclastic activities of RAW264.7 cells, as compared with the EM-TCP scaffolds. In vivo assessment results indicated that at postoperative week 6, new vessels and a large percentage of new bone tissues (24-25%) were formed throughout the interconnected macropores of EM-TCP and EM-TCP/SrPG, which were implanted in the femoral defects of rabbits; the bone formation of the EM-TCP group was comparable to that of the EM-TCP/SrPG group. At 12 weeks postimplantation, the bone formation percentage of EM-TCP was slightly reduced, while that of EM-TCP/SrPG with a slower degradation rate was pronouncedly increased. This work provides a new strategy to fabricate interconnected bioceramic scaffolds allowing for fast bone regeneration, and the EM-TCP/SrPG scaffolds are promising for efficiently repairing bone defects.

In-vivo evaluation of a partially resorbable poly l-lactic acid/ braided bioactive glass fibers reinforced composite for load bearing fracture fixation.

Our previous studies have been focused on the design, optimization and manufacture of a partially resorbable composite bone plate consisting of a poly l-lactic acid matrix reinforced with braided fabrics bioactive glass fibers (PLLA/BG). In the present study, the response of the composite samples, the degradation rate, the inflammatory response, fibrous capsule formation and tissue-implant bonding to the in-vivo environment were assessed via implantation in the rabbit subcutaneous tissue. Despite the presence of both enzymatic degradation and hydrolysis processes within the body, the rate of the molecular weight loss as an indicator of degradation did not show a significant difference with the in-vitro conditions. It was predicted that strength loss would show the same trend since it was a consequence of molecular chain disruption and the loss of molecular weight. Inexistence of chronic inflammation, as confirmed by our previous results on the controlled degradation rate, also showed the maintenance of the physiological pH in the peripheral environment of the implant. Moreover, lack of the fibrous capsule tissue around the implant indicated that the implant was bioactive. In addition, given the composition of the bioactive glass fibers, that could be bonded to soft and hard tissues, tissue bonding with the PLLA/BG composite samples was also observed, thereby confirming the bioactivity and biocompatibility of the proposed bone plate.

First successful stabilization of consolidated amorphous calcium phosphate (ACP) by cold sintering: toward highly-resorbable reactive bioceramics.

In the field of bone regeneration, some clinical conditions require highly-resorbable, reactive bone substitutes to rapidly initiate tissue neo-formation. In this view, Amorphous Calcium Phosphates (ACP) appear as well suited bioceramics taking into account their high metastability. However, the metastability also leads to difficulties of sintering without transformation into crystalline compounds. In this work, various calcium phosphate samples (co)doped with carbonate (CO32-) and magnesium ions were synthesized by the double decomposition method in alkaline media using ammonium and potassium hydroxide solutions. The obtained amorphous powders possess an exceptionally-high carbonate content up to 18.3 wt%. Spark Plasma Sintering (SPS) at very low temperature (150 °C) was then utilized to consolidate initial powders with the view to preserve their amorphous character. The influence of the introduction of different apatite growth inhibitors such as carbonate (CO32-) and magnesium ions was studied. XRD and FTIR analyses revealed that sintered ceramics generally consisted in highly carbonated low-crystallinity apatites, which are expected to have higher solubility than conventional apatite-based systems. However, most interestingly, modulation of the doping conditions allowed us to retain, for the first time, the amorphous character of ACP powders after SPS. Such consolidated ACP compounds may now be considered as a new family of bioceramics with high metastability allowing the fast release of bioactive ions upon resorption.