Osteoconductive Ceramics Research Articles

Osseointegration enhancement by controlling dispersion state of carbonate apatite in polylactic acid implant

Osteoconductive ceramics (OCs) are often used to endow polylactic acid (PLA) with osseointegration ability. Conventionally, OC powder is dispersed in PLA. However, considering cell attachment to the implant, OCs may be more favorable when they exist in the form of aggregations, such as granules, and are larger than the cells rather than being dispersed like a powder. In this study, to clarify the effects of the dispersion state of OCs on the osseointegration ability, carbonate apatite (CAp), a bone mineral analog that is osteoconductive and bioresorbable, powder–PLA (P-PLA), and CAp granule–PLA (G-PLA) composite implants were fabricated via thermal pressing. The powder and granule sizes of CAp were approximately 1 and 300–600 µm, respectively. G-PLA exhibited a higher water wettability and released calcium and phosphate ions faster than P-PLA. When cylindrical G-PLA, P-PLA, and PLA were implanted in rabbit tibial bone defects, G-PLA promoted bone maturation compared to P-PLA and pure PLA. Furthermore, G-PLA bonded directly to the host bone, whereas P-PLA bonded across the osteoid layers. Consequently, the bone-to-implant contact of G-PLA was 1.8- and 5.6-fold higher than those of P-PLA and PLA, respectively. Furthermore, the adhesive shear strength of G-PLA was 1.9- and 3.0-fold higher than those of P-PLA and PLA, respectively. Thus, G-PLA achieved earlier and stronger osseointegration than P-PLA or PLA. The findings of this study highlight the significance of the state of dispersion of OCs in implants as a novel strategy for material development.

Functionally gradient magnesium-based composite for temporary orthopaedic implant with improved corrosion resistance and osteogenic properties

Magnesium (Mg) is a potential alternative for conventional orthopaedic implant materials owing to its biodegradation behavior and physical characteristics similar to natural human bone. Due to its biomimetic mechanical attributes, Mg in orthopaedic applications could reduce the risk of the ‘stress shielding effect’. However, the major limitation of Mg is its high in-vivo corrosion rate. Thermal sprayed coatings of osteoconductive ceramics like hydroxyapatite (HA) have been explored as a potential solution, albeit with limited success due to the low melting point of Mg, which restricts the ease of fabricating surface-adherent ceramic coating. The present study focuses on overcoming this limitation through a Mg-HA functionally gradient material (FGM) system, which is expected to provide a highly corrosion-resistant surface and uniform mechanical integrity throughout the structure. In addition to corrosion resistance, the FGM system has improved biocompatibility and osteoconductivity without compromising its mechanical stability. The FGM, with a compositional gradient of Mg-HA composite, consisting of Mg at the core and increasing HA towards the outer layer, has been fabricated through spark plasma sintering. Mechanical properties of the overall structure were better than those of the best individual composite. More importantly, corrosion resistance of the FGM structure was significantly improved (~154%) as compared to individual composites. In addition, alkaline phosphatase activity, osteogenic gene expression and cell viability, all pertaining to efficient osteogenic differentiation, were enhanced for FGM and 15 wt% HA reinforced composites. These observations suggest that the FGM structure is promising for temporary biodegradable orthopaedic implants.

The Use of Sucrose Granule as Pore Maker in Preparation of Porous Calcium Sulfate Dihydrate

Calcium sulfate dihydrate (CSD) has been clinically used as bone filler for decades. CSD bone graft is cheap, biocompatible and can be transformed to other osteoconductive ceramics such as hydroxyapatite and carbonate apatite. In addition, porous ceramic bone grafts is desired clinically. Development of porous ceramics bone graft with simple and cost-effective method is preferred. Thus, in this study, porous CSD was developed. Porous CSD can be used both as bone filler or precursor for porous hydroxyapatite and carbonate apatite. Porous CSD was prepared by mixing calcium sulfate hemihydrate (CSH) containing sucrose granules with distilled water. After setting, the sucrose granules were removed by immersion in distilled water. Porous CSD was obtained after sucrose leaching. It was observed that more pore formed in the specimen with 50% sucrose granule compared with that of 25% sucrose granule. The sucrose was completely removed from the porous CSD evident from ATR-FTIR analysis. The diametral tensile strength of the porous CSD tend to decrease with the increase of sucrose granule. Finally, sucrose granule was feasible to be used as pore maker in preparation of porous CSD.

Functional self-assembled neocartilage as part of a biphasic osteochondral construct.

Bone-to-bone integration can be obtained by osteoconductive ceramics such as hydroxyapatite (HAp) and beta-tricalcium phosphate (β-TCP), but cartilage-to-cartilage integration is notoriously difficult. Many cartilage repair therapies, including microfracture and mosaicplasty, capitalize on the reparative aspects of subchondral bone due to its resident population of stem cells and vascularity. A strategy of incorporating tissue engineered neocartilage into a ceramic to form an osteochondral construct may serve as a suitable alternative to achieve cartilage graft fixation. The use of a tissue engineered osteochondral construct to repair cartilage defects may also benefit from the ceramic’s proximity to underlying bone and abundant supply of progenitor cells and nutrients. The objective of the first study was to compare HAp and β-TCP ceramics, two widely used ceramics in bone regeneration, in terms of their ability to influence neocartilage interdigitation at an engineered osteochondral interface. Additional assays quantified ceramic pore size, porosity, and compressive strength. The compressive strength of HAp was six times higher than that of β-TCP due to differences in porosity and pore size, and HAp was thus carried forward in the second study as the composition with which to engineer an osteochondral construct. Importantly, it was shown that incorporation of the HAp ceramic in conjunction with the self-assembling process resulted in functionally viable neocartilage. For example, only collagen/dry weight and ultimate tensile strength of the chondral control constructs remained significantly greater than the neocartilage cut off the osteochondral constructs. By demonstrating that the functional properties of engineered neocartilage are not negatively affected by the inclusion of an HAp ceramic in culture, neocartilage engineering strategies may be directly applied to the formation of an osteochondral construct.

An ECM-Mimicking, Mesenchymal Stem Cell-Embedded Hybrid Scaffold for Bone Regeneration.

While biologically feasible, bone repair is often inadequate, particularly in cases of large defects. The search for effective bone regeneration strategies has led to the emergence of bone tissue engineering (TE) techniques. When integrating electrospinning techniques, scaffolds featuring randomly oriented or aligned fibers, characteristic of the extracellular matrix (ECM), can be fabricated. In parallel, mesenchymal stem cells (MSCs), which are capable of both self-renewing and differentiating into numerous tissue types, have been suggested to be a suitable option for cell-based tissue engineering therapies. This work aimed to create a novel biocompatible hybrid scaffold composed of electrospun polymeric nanofibers combined with osteoconductive ceramics, loaded with human MSCs, to yield a tissue-like construct to promote in vivo bone formation. Characterization of the cell-embedded scaffolds demonstrated their resemblance to bone tissue extracellular matrix, on both micro- and nanoscales and MSC viability and integration within the electrospun nanofibers. Subcutaneous implantation of the cell-embedded scaffolds in the dorsal side of mice led to new bone, muscle, adipose, and connective tissue formation within 8 weeks. This hybrid scaffold may represent a step forward in the pursuit of advanced bone tissue engineering scaffolds.

Efficacy of Osteoconductive Ceramics in Bioresorbable Screws for Anterior Cruciate Ligament Reconstruction: A Prospective Intrapatient Comparative Study.

Background:Osteoconductive additives are used in resorbable interference screws for anterior cruciate ligament (ACL) reconstruction to improve graft incorporation and mitigate adverse effects. There are no published studies that compare biological performances of bioresorbable and biocomposite screws without artifacts due to different follow-up times and intrinsic patient characteristics.Purpose/Hypothesis:The purpose of this study was to evaluate the efficacy of osteoconductive agents in bioresorbable screws for ACL reconstruction at minimum follow-up of 2 years by intrapatient comparison. The hypothesis was that osteoconductive ceramics would result in slower resorption, improved ossification, and less tunnel widening.Study Design:Cohort study; Level of evidence, 2.Methods:A total of 28 ACL reconstructions at 2 centers were randomly assigned into 2 comparable groups: (1) the graft was fixed in the tibia using standard bioresorbable screws and in the femur using biocomposite screws with osteoconductive agents (biphasic calcium phosphate), and (2) the graft was fixed in the femur using a standard bioresorbable screw and in the tibia using a biocomposite screw with osteoconductive agents.Results:Twenty-seven patients completed evaluations at 29.9 ± 4.0 months. Resorption was complete for more bioresorbable (81%) than biocomposite (37%) screws (P = .0029), whereas satisfactory ossification was observed in more biocomposite (52%) than bioresorbable (15%) screws (P = .0216). The tunnel shape was normal in more biocomposite (81%) than bioresorbable (48%) screws (P = .0126), and marked cortical formation was twice more frequent for biocomposite (78%) than bioresorbable (37%) screws (P = .0012). Bioresorbable screws exhibited faster resorption in the femur (P = .0202) but not in the tibia (not significant). Conversely, biocomposite screws demonstrated better ossification, less tunnel widening, and more cortical formation in the tibia (P < .0001, P = .0227, and P < .0001, respectively) but not in the femur (not significant for all).Conclusion:Osteoconductive additives can reduce the extent of resorption while improving ossification, reducing tunnel widening, and increasing cortical formation.Clinical Relevance:The benefits of osteoconductive agents justify their associated costs for ACL reconstruction, particularly in the tibia.

Osteoconductive ceramics with a specified system of interconnected pores based on double calcium alkali metal phosphates

Osteoconductive ceramics with a specified system of interconnected pores based on double calcium alkali metal phosphates

Use of bone graft replacement in spinal fusions

The rationale for the increasing use of bone graft replacement lies in the need for increased graft volume, the avoidance of typical autograft donor site morbidity, and the potential improvement of fusion rates in revision and complex reconstructive surgery. The purpose of this work is to offer the spinal surgeon an evidence-based guide for choosing the appropriate grafting material and for using it effectively. Evidence-based overview of physical and biological properties, clinical indications and results of osteoconductive and osteoinductive bone replacement materials. The ideal bone replacement material should be osteoinductive and conductive, non-pathogenic, minimally antigenic, and (if required) mechanically stable. Compared to autograft, vascularization and remodeling of the fusion mass are delayed using allograft. Allogenous bone and demineralized bone matrix (DBM) possess limited osteoinductive properties and carry the risk of potential infectious disease transmission. Plasma-rich plasma (PRP) and bone marrow aspirate are commonly used in conjunction with an osteoconductive carrier materials. On-label use of bone morphogenetic proteins (BMPs) is currently restricted to mono- and bisegmental anterior lumbar fusion. The fusion rates obtained with BMPs match those of autologous bone graft. Potential risks of rhBMP in clinical use include soft tissue reactions, radiculitis and potentially increased risk of cancer. Osteoconductive ceramics (HA, CC, CS, ß-TCP) are useful graft extenders and carriers for bone growth enhancers and antibiotics. Osteoconductive bioceramics with different mechanical and biological properties are available for use as graft extenders. In a defined group of anterior interbody fusion procedures (ACDF, ALIF), satisfactory fusion rates (> 90%) may be obtained with exclusive use of graft extenders, whereas their solitary use in posterolateral fusions is not advisable. Genuine bone replacement is currently feasible with BMPs. Their use should be restricted to specific indications such as complex revision surgery and pseudarthrosis.

Primary cancellous bone formation around micro-chambered beads

ObjectivesThe question has been raised whether benign bone defects in patients can be treated with bone forming osteoconductive ceramics achieving primarily a cancellous bone scaffold, which is under load from the beginning. Materials and methodsTen reconstructions were performed in 9 patients (6 women and 3 male), with a mean age of 49 (25–65)years, suffering a high variety of epi- and metaphyseal defects, four tibial fractures, two calcaneal fractures, one pathological phalangeal fracture, one chondroma of the distal femur and two open-wedge osteotomies were filled with micro-chambered ceramic beads of 4 and 6mm in diameter. The mean follow-up was 22 (7–8)months. X-rays and CT-scans formed the basis for the evaluation of the reconstruction of the cancellous bone scaffolds. ResultsAll cancellous structures were rebuilt, if completely filled with bone-forming elements. If the filling was incomplete, no physiological cancellous bone scaffold resulted. The β-TCP micro-chambered beads were completely reabsorbed or sandwich-like incorporated at the time of evaluation. The HA micro-chambered beads revealed a contrast enhancement and were integrated in the osseous construction of the bone scaffold. ConclusionPrimary cancellous bone formation can be achieved with osteoconductive ceramic micro-chambered beads and can be combined with any osteosynthesis for stable fixation.

Formación de hueso esponjoso con esferas microcompartimentales

ObjectivesThe question has been raised whether benign bone defects in patients can be treated with bone forming osteoconductive ceramics achieving primarily a cancellous bone scaffold, which is under load from the beginning. Material and methodsTen reconstructions were performed in 9patients (6women and 3male), with a mean age of 49 (25-65)years, suffering a high variety of epi- and metaphyseal defects, four tibial fractures, two calcaneal fractures, one pathological phalangeal fracture, one chondroma of the distal femur and two open-wedge osteotomies were filled with micro-chambered ceramic beads of 4 and 6mm in diameter. The mean follow up was 22 (7- 8)months. X-rays and CT-scans formed the basis for the evaluation of the reconstruction of the cancellous bone scaffolds. ResultsAll cancellous structures were rebuilt, if completely filled with bone-forming elements. If the filling was incomplete, no physiological cancellous bone scaffold resulted. The β-TCP micro-chambered beads were completely reabsorbed or sandwich-like incorporated at the time of evaluation. The HA micro-chambered beads revealed a contrast enhancement and were integrated in the osseous construction of the bone scaffold. ConclusionPrimary cancellous bone formation can be achieved with osteoconductive ceramic micro-chambered beads and can be combined with any osteosynthesis for stable fixation.

Strength Characteristics of Resorbable Osteoconductive Ceramics Based on Diphosphates of Calcium and Alkali Metals

3 An investigation into the strength characteristics of ceramics based on diphosphates Ca(3-x)�F 2x(PO4)2 (x = 0-1 andF = Na, K) provides evidence of composition strengthening in the range х = 0.6-0.8 containing the greatest amount of the supercooled high-temperature modification α-�KZFJH 4. The method of high- temperature x-ray diffractometry is used to examine thermal expansion of rhenanite phases ofKZFJH 4.

How bone forms in large cancellous defects: Critical analysis based on experimental work and literature

The behaviour of physiological biomaterials, β-tricalciumphosphate and hydroxyapatite, is analysed based on current literature and our own experimental work.The properties of graft substitutes based on ceramic materials are clearly defined according to their scientific efficiency. The strength of the materials and their biodegradability are still not fully evaluated. Strength and degradability have a direct proportional relationship and are considered the most efficient way to be adapted by their properties to the needs for the treatment of bone defects. New technologies for the manufacturing process are presented that increase those properties and thus open up new indications and easier application of the ceramic materials. The implantation process as well is carefully validated by animal experiments to avoid failures. Based on the experiments, a completely new approach is defined as to how primary bone formation with osteoconductive ceramics can be achieved. The milestones in that approach comprise a synthetically manufactured replica of the bone marrow spaces as osteoconductive ladder, whereas the bead is defined as bone-forming element. As a result, materials are available with high strength if the ceramic is solid or highly porous and possesses a micro-structure. The injection moulding process allows for the combination of high strength of the material with high porosity. Based on the strong capillary forces, micro-chambered beads fulfil most expectations for primary bone formation in cancellous bone defects, including drug delivery, mechanical strengthening if necessary, and stable implantation in situ by coagulation of the blood and bone marrow suctioned in.

BENIGN BONE TUMORS AND TUMOR-LIKE BONE LESIONS: TREATMENT UPDATE AND NEW TRENDS

The treatment of benign bone tumors (BBT) and tumor-like bone lesions (TBL) has observed the introduction of new drugs, such as intravenous bisphosphonates, which have ossified bone lesions caused by fibrous dysplasia. Aneurismal bone cyst has been treated with sclerosing agents by percutaneous injection, yielding good results. Adjuvants allow joint salvage, maintenance of movements and function, with low rates of recurrence. Among them, the most used ones are bone cement (PMMA), phenol, nitrogen-based cryotherapy, hydrogen peroxide, ethanol and radiotherapy. New methods of treatment include thermal ablation with radiofrequency and laser, mainly utilized for treating osteoid osteoma. Arthroscopy allows resection of benign intra-joint lesions and assists the surgery of subchondral tumors. A great advance is the utilization of synthetic bone substitutes, which are a mixture of osteoinductive growth factors and osteoconductive ceramics, and have presented comparable results to autogenous bone grafts. There is a recent trend for closed treatments, with percutaneous injection of demineralized bone matrix (DBM) and calcium sulfate. Autogenous cancellous bone graft remains as the gold standard. Vascularized fibula graft, on the other hand, incorporates faster in the treatment of large destructive lesions. Also, allogenic cortical support allows structural augmentation for aggressive tumors. Freeze-dried allografts are used to fill contained defects and as expanders of autografts. Joint endoprosthesis may be used in large destructive lesions of the distal femur, hip and shoulder.

Nerve growth factor beta(NGF beta) delivery via a collagen/hydroxyapatite (Col/HAp) composite and its effects on new bone ingrowth.

In craniofacial surgery, bone is needed to augment misshapen areas and to fill gaps during repair of congenital anomalies and injuries resulting into bone deficiencies. Examples of conditions requiring bone tissue include missing alveolar bone in cleft palates, bony nasal pyramid defects following removal of fistulous tracts or cysts and defects following removal of sinus and mandibular tumors. Moreover, maxillofacial neurosensory deficiencies may be caused by various surgical procedures, such as tooth extraction, osteotomies, pre-prosthetic procedures, excision of tumors or cysts, surgery of TMJ, and surgical treatment of fractures and cleft lip/palate. Therefore, a tissue engineering approach to craniofacial surgery has a crucial importance: the use of various composites with osteoconductive ceramics, polymers, bioactive factors, cells, or a combination of them, offers the possibility of rapid tissue regeneration and integration with the host tissue. In this study, a composite consisting of two well-known biomaterials, collagen/hydroxyapatite (Col/HAp), was used as a drug delivery device for neurotrophin - nerve growth factor beta (NGF beta). This delivery device, enriched with neurogenic-osteogenic factor, was analyzed in vitro and in vivo. It was implanted into calvaria defects of 20 Wistar rats, weighing 200-250 g. Implants were left in place for different periods of time. Controls were as follows: (a) contralateral defect without any implant; and (b) contralateral defect implanted with composite without NGF factor. The rats were euthanized after 30 days, and the implant sites and explants were examined clinically, histologically, SEM and histomorphometrically. Our results evidenced stimulation of periosteal and endocortical woven and lamellar bone formation, with increases in bone mass and decreases in bone marrow. We found that NGF enhanced the remodeling activity in the intracortical region, and induced an increase in the intracortical cavity number and area by the end of the study. In vitro results were in line with in vivo ones. We believe that the composite proposed in this study has considerable advantages in tissue engineering and is very suitable as a biomaterial for the filling of irregular defects in maxillo-facial surgery. Two areas of clinical research will be impacted by this system. The first is pharmaceutical research on drug delivery and high-throughput screening of neurotrophic-osteogenic compounds. Transplantation research is the second area that will benefit from the system.