Hydroxyapatite Bone Scaffolds Research Articles

Experimental and numerical investigations for compressive behavior of porous hydroxyapatite bone scaffold fabricated via freeze-gel casting method

Artificial bone scaffolds with a porosity of ≥64% were manufactured using hydroxyapatite (HA). The Freeze-gel Casting method using tert-butyl alcohol (TBA) as a solvent was adopted to maintain proper mechanical strength. The manufactured HA scaffold had excellent internal connectivity owing to the continuous connection of the long columnar pores and arrangement of the constant pore walls. For the HA scaffold, compression tests at different strain rates under uniaxially compressed loads were performed, and the compressive behavior according to the strain rate was analyzed. A maximum yield stress of 2–3 MPa was observed, and the overall compressive behavior was divided into elastic, plateau, and densification sections, which were different from the brittleness behavior of ordinary ceramics and similar to that of polymer materials. The compressive behavior of the HA scaffold was successfully simulated by applying the Frank–Brockman–Zairi constitutive model used to simulate elasto-viscoplastic material behavior. Seven material parameters belonging to the constitutive equation were proposed for the HA scaffold by adopting a deterministic approach for material parameter identification. Models can be developed from methods for simulating the mechanical behavior of a porous ceramic scaffold to predict the long-term mechanical behavior of the scaffold inserted in vivo, which may help in bone defects recovery.

Modification of hydroxyapatite (HA) powder by carboxymethyl chitosan (CMCS) for 3D printing bioceramic bone scaffolds

The poor mechanical properties of 3D printed HA bone scaffold is always a challenge in tissue engineering, to address this issue, carboxymethyl chitosan (CMCS) was proposed to modify HA bone scaffolds by a physical blending method in this research. A series of HA and HA/CMCS composite ceramic scaffolds were printed by using piezoelectric inkjet 3D printing technology, and their properties were investigated in terms of forming quality, structural morphology, mechanical properties, degradability, cytotoxicity, and cell adhesion growth. The results of forming quality and structural morphology show that with the increase of CMCS content, the forming quality of the samples deteriorated, the pore size and porosity increased. However, when the content of CMCS reached 5 wt%, obvious cracks appeared on the surface of the sample, and the forming quality was relatively poor. The mechanical testing results indicated the toughness of composites could be enhanced by incorporating CMCS into HA, which was attributed to the higher strength connections of the CMCS polymer network between HA particles and the stronger interaction between HA and CMCS molecules. FTIR spectra further revealed the strong hydrogen bonding interaction between CMCS and HA. Moreover, the degradation rate and mineralization ability of the sample increased with the content of CMCS, but the compressive strength during degradation increased with the CMCS content, indicating that incorporating CMCS into HA cannot only improve the mechanical property and biological activity of the scaffold but also makes up the defect of slow degradation of pure HA scaffold. Finally, the cytotoxicity, cell adhesion, and cell proliferation tests show that HA and HA/CMCS composite samples had good cytocompatibility, HA/CMCS sample with 3 wt% CMCS possessed the best bioactivity. In summary, HA/CMCS composite powder with 3 wt% CMCS content is the optimal matrix material for 3D printing bone scaffolds.

Tissue-Engineered Hydroxyapatite Bone Scaffold Impregnated with Osteoprogenitor Cells Promotes Bone Regeneration in Sheep Model.

Managing massive bone defects, a great challenge to orthopaedics reconstructive surgery. The problem arise is the supply of suitable bone is limited with many complications. Tissue-engineered hydroxyapatite bone (TEHB) scaffold impregnated with osteoprogenitor cells developed as an alternative to promote bone regeneration. This animal protocol has been approved by Universiti Kebangsaan Malaysia Animal Ethical Committee. The TEHB scaffold prepared from hydroxyapatite using gel casting method. A total of six adolescent female sheep were chosen for this study. Later, all the sheep were euthanized in a proper manner and the bone harvested for biomechanical study. Bone marrow was collected from iliac crest of the sheep and bone marrow stem cells (BMSCs) isolated and cultured. BMSCs then cultured in osteogenic medium for osteoprogenitor cells development and the plasma collected was seeded with osteoprogenitor cells mixed with calcium chloride. Bone defect of 3cm length of tibia bone created from each sheep leg and implanted with autologous and TEHB scaffold in 2 different groups of sheep. Wound site was monitored weekly until the wound completely healed and conventional X-ray performed at week 1 and 24. Shear test was conducted to determine the shear force on the autologous bone and TEHB scaffold after implantation for 24weeks. All of the sheep survived without any complications during the study period and radiograph showed new bone formation. Later, the bone harvested was for biomechanical study. The highest shear force for the autologous group was 13MPa and the lowest was 5MPa while for the scaffold group, the highest was 10MPa and the lowest was 3MPa. Although, proximal and distal interface of autologous bone graft shows higher shear strength compared to the TEHB scaffold but there is no significant difference in both groups, p value > 0.05. Histologically in both proximal and distal interface in both arms shows bone healing and woven bone formation. TEHB scaffold impregnated with osteoprogenitor cells has the potential to be developed as a bone substitute in view of its strength and capability to promote bone regeneration.

3D printing and osteogenesis of loofah-like hydroxyapatite bone scaffolds

Repair of metabolic function in large bone defect remains a critical challenge, which largely depends on the osteogenic property of bone scaffold. Furthermore, microporous structure is one of the most critical factors that influence the osteogenic performance of bone scaffold. Therefore, it is an effective method to explore porous structures aiming at promoting osteogenesis. In this work, hydroxyapatite, the most abundant inorganic substance in bone tissue, was considered the research material. Furthermore, a natural loofah with high porosity and connectivity was selected as the bionic structure to reconstruct a porous bone scaffold based on 3D printing. Four types of loofah-like bone scaffolds were reconstructed and fabricated, and they all have an appropriate pore size and complex internal structure with a desirable porosity. According to the osteogenic ability analyses of micro-CT and histological morphometric, the BV/TV data of Type Ⅱ could reach 33%. The bone formation was found in pores and deep, rugged surfaces of scaffolds. The bionic bone scaffolds can promote in vivo osteogenesis, confirming the utility of our designed bionic scaffolds for bone regeneration.

Low-temperature fabrication of calcium deficient hydroxyapatite bone scaffold by optimization of 3D printing conditions

We herein propose a novel low-temperature fabrication process of calcium deficient hydroxyapatite (CDHA) 3D scaffolds for bone tissue regeneration through a combination of material extrusion type 3D printing process and bone cement chemistry. The CDHA scaffolds with high porosity of 70% showed excellent mechanical property of 25 MPa (compressive strength), without any sintering process after 3D printing. By using this method, the final structures do not show size shrinkage, which must be considered in conventional ceramic sintering processes. We could therefore achieve both size- and 3D architecture-controlled porous CDHA scaffolds with high accuracy. In addition, the resulting ceramic cement scaffolds were not brittle and could be machined without chipping or fracturing the scaffold. The complete process takes place at physiological conditions (37 °C, pH=7), and heat sensitive drugs and biomolecules could be directly loaded onto the raw powder and achieve homogeneous distribution throughout the CDHA scaffold. In this study, we discuss various key factors to complete this low-temperature 3D printing fabrication of calcium phosphate, such as the pre-treatment conditions of particles, liquid-to-powder ratio, relationships between strut sizes, infill of structures, setting temperatures and the properties of 3D printed scaffolds. The low-temperature fabrication process of calcium phosphate scaffolds developed in this study has excellent potential for use in bone tissue engineering.

Microstructure, mechanical properties and in vitro biocompatibilities of a novel bionic hydroxyapatite bone scaffold prepared by the addition of boron nitride

Hydroxyapatite (HA) is an ideal bone insert material due to its biocompatibility and osteoconductivity, but the poor mechanical properties limit its wide application in clinical practice. The aim of this work is to fabricate a novel composite that with similar porous structure to cortical bone and high mechanical properties by the addition of boron nitride (BN) and sintered in air at 1250 °C for 40 min. In mechanical properties, the maximum flexural strength, elastic modulus and fracture toughness are 94.04 MPa, 69.46 GPa and 1.16 MPa m1/2, respectively, which are improved by 20.56%, 12.87% and 8.41%, respectively. In the microscopy of surface and fracture surface, the porous structure similar to cortical bone is observed. There are microscale and nanoscale pores, and the pores present an interconnected structure. In vitro biocompatibility assessment, the addition of BN and its reaction product have no adverse effect on osteoblast viability, which even promotes osteogenic differentiation and mineralization.

The printability of three water based polymeric binders and their effects on the properties of 3D printed hydroxyapatite bone scaffold

As the basic material of 3D printing, the binder is the key factor to a successful 3D printing process as it determines the property and structure of the printed bone scaffolds, as well as the reliability of the entire printing system. In this study, three commonly used polymeric binders (PVA, PVP and PAM) were applied to fabricate HA embryonic scaffolds by powder-based 3D printing technology. The suitable printing concentrations of three binders were screened by investigating their printability and drop penetration. Following, based on the printable binders, different scaffold samples were fabricated and characterized. And the effects of different binders on the properties of scaffolds were investigated in terms of mechanical properties and cell attachment. Results show that the binder of 1.0 wt% PVA and its scaffolds possess the best the printing resolution, solidification ability and compressive strength, while the binder of 1.5 wt% PVP and its scaffolds possess the shortest penetration time and the largest compressive modulus. Additionally, the cell culture experimental results demonstrate that the scaffolds printed with 1.0 wt% PVA process the best cytocompatibility and are most conducive to cell attachment among three binders. Therefore, comprehensive considering the current results of three binders we conclude that among three binders the binder of 1.0 wt% PVA is most suitable for fabricating HA bone scaffolds by 3D printing technology.

Characterization of Mechanical and Micro-Architectural Properties of Porous Hydroxyapatite Bone Scaffold Using Green MicroAlgae as Binder

Novel Hydroxyapatite (HA)-based porous bone scaffold is developed using green microalgae as binding as well as pore-forming agent. The composite scaffolds are developed at 1:2, 2:1 and 1:1 (w/w) compositions of HA and binder, respectively, using solvent-casting technique and their mechanical and micro-architectural properties are investigated. Material characterization of the scaffold shows improved mechanical strength with a maximum compressive strength of 2.89 MPa and maximum interconnected porosity of 65.29%. FT-IR and XRD results confirm formation of crystalline nano-HA in the scaffolds. SEM and TEM micrographs of the scaffolds show pore morphology with a maximum pore diameter of 258 microns and minimum pore diameter of 6 microns and uniformly dispersed rod-shaped nano-HA particles of length 3.95–99.11 nm, respectively. TG/DTG analysis shows high thermal stability of scaffolds with high HA content. Comparative study of the three types of scaffolds shows composites with equal weight ratio of HA, and binder yields the highest porosity and mechanical strength desired for cell growth and support. XRF analysis confirms Ca and P as the major constituent elements of the scaffold. The study highlights the potential of natural biomass as an alternative to synthetic and naturally derived polymeric binders for development of HA-based bone scaffolds.

Additive manufacturing of hydroxyapatite bone scaffolds via digital light processing and in vitro compatibility

The bioceramic material hydroxyapatite (HA) is widely used in the field of bone repair. Based on additive manufacturing (AM) techniques, HA is fabricated with complex geometry to satisfy biomedical application requirements. Digital light processing (DLP) is a promising AM technique that is capable of producing HA parts with high accuracy and efficiency. The fabrication of HA parts using DLP is investigated in this study. Properties of the HA ceramic slurry and the process parameters of curing, debinding, and sintering are initially examined. The mechanical properties, porosity, and shrinkage of the sintered samples is then investigated. The experimental results show that ceramic samples with density above 90%, microhardness up to 270 HV, and flexural strength of 41.3 MPa can be manufactured using the DLP method. Hydroxyapatite bone scaffolds are then prepared with pore sizes of 300–600 μm, porosity of about 49.8%, and compressive strength of 15.25 MPa, and the scaffolds are cultured with osteoblast precursor cells to detect biocompatibility. Results illustrate that the produced scaffolds possess strong biocompatibility and can promote osteoblast proliferation, adhesion, and differentiation. The HA bone scaffolds fabricated by DLP AM show strong potential to fulfill a constructive role in the medical field of human bone repair.

The Transplantation of hBM-MSCs Increases Bone Neo-Formation and Preserves Hearing Function in the Treatment of Temporal Bone Defects - on the Experience of Two Month Follow Up.

Temporal bone reconstruction is a persisting problem following middle ear cholesteatoma surgery. Seeking to advance the clinical transfer of stem cell therapy we attempted the reconstruction of temporal bone using a composite bioartificial graft based on a hydroxyapatite bone scaffold combined with human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The aim of this study was to evaluate the effect of the combined biomaterial on the healing of postoperative temporal bone defects and the preservation of physiological hearing functions in a guinea pig model. The treatment's effect could be observed at 1 and 2months after implantation of the biomaterial, as opposed to the control group. The clinical evaluation of our results included animal survival, clinical signs of an inflammatory response, and exploration of the tympanic bulla. Osteogenesis, angiogenesis, and inflammation were evaluated by histopathological analyses, whereas hBM-MSCs survival was evaluated by immunofluorescence assays. Hearing capacity was evaluated by objective audiometric methods, i.e. auditory brainstem responses and otoacoustic emission. Our study shows that hBM-MSCs, in combination with hydroxyapatite scaffolds, improves the repair of bone defects providing a safe and effective alternative in their treatment following middle ear surgery due to cholesteatoma.

Strategies to Improve Bioactivity of Hydroxyapatite Bone Scaffolds

Two different approaches are proposed in this study to enhance the bioactivity of hydroxyapatite-based scaffolds for bone tissue regeneration. The first method consists in a structural modification of Hydroxyapatite (HA) through doping it with Magnesium (1,3% wt) while the second one in using HA in combination with a calcium silicate, i.e. Wollastonite (WS), to form a composite bioceramic. Scaffolds with high and strongly interconnected porosity (pores ranging from 300 to 800 µm) were produced throughout both procedures. Higher mechanical properties in compression were obtained when the composite Ws/HA bioceramic was adopted. That one showed a weight loss after 6 months in physiological solution seven times higher than doped HA. Preliminary in vitro tests highlighted that both kinds of scaffold allowed the adhesion of MG63, without significant differences in terms of vitality, indicating a good biocompatibility of both used biomaterials.

Chitosan/β-1,3-glucan/hydroxyapatite bone scaffold enhances osteogenic differentiation through TNF-α-mediated mechanism

The role of TNF-α in bone healing process is still unclear and controversial. Although it is commonly believed that TNF-α inhibits osteogenic differentiation, there are few reports that identified a crucial role of TNF-α in enhancing bone regeneration process. The aim of this study was to prove that novel chitosan/β-1,3-glucan/HA scaffold (chit/glu/HA) may promote osteogenic differentiation via TNF-α-mediated mechanism and an autocrine stimulation of osteoblasts. It was demonstrated that normal human fetal osteoblasts (hFOB 1.19) maintained in conditioned medium containing increased level of TNF-α and harvested from hFOB 1.19 cells cultured on the chit/glu/HA scaffold (CM-chit/glu/HA) were in more advanced phase of osteogenic differentiation compared to the osteoblasts cultured in non-conditioned osteogenic medium and conditioned medium harvested from hFOB 1.19 cells cultured on the polystyrene plate. Cells cultured in CM-chit/glu/HA produced significantly more Col I protein, revealed 2-fold higher bALP activity, deposited 3-fold more calcium phosphate, and formed mineralized nodules. Thus, it was demonstrated that novel chit/glu/HA scaffold is promising material for bone regeneration applications to stimulate accelerated new bone formation as it enhances osteogenic differentiation via increasing TNF-α production by osteoblasts.

Can European Sea Bass (<i>Dicentrarchus labrax</i>) Scale Be a Good Candidate for Nano-Bioceramics Production?

Bioceramics are commonly used biomaterials for orthopedic and dental applications. Among these bioceramics, hydroxyapatite (HA) and tricalcium phosphate (TCP) are of interest and are used in various biomedical applications. Production of bioceramics from natural materials such as bovine and sheep bones with calcination method, is possible. Lately, fish scales become an alternative biological source for bioceramic production. The present study proposes an approach to obtain HA bone-scaffolds from European Sea Bass (Dicentrarchus labrax) scales aiming to provide nano-biomaterials via calcination method. Untreated fish scales are obtained and are carefully cleaned from their meat and grease. They are washed with alkaline water several times and calcinated at 850°C for 4 hours. Energy Dispersive Spectroscopy (EDS), X-ray diffraction analysis, Scanning Electron Microscopy (SEM) studies are performed. Various calcium phosphate species (HA, TCP) are identified in the study. SEM images prove the presence of the nano-scale structures. This study indicates calcination as a simple way of nano-scale bioceramic production for drug delivery and tissue engineering applications. Being produced from wastes of a sustainable and cheap source, these bioceramics can be good candidates for future clinical applications.

Study the bonding mechanism of binders on hydroxyapatite surface and mechanical properties for 3DP fabrication bone scaffolds: A molecular dynamics method

Event Abstract Back to Event Study the bonding mechanism of binders on hydroxyapatite surface and mechanical properties for 3DP fabrication bone scaffolds: A molecular dynamics method Qinghua Wei1, Yanen Wang1, Xinpei Li1, Mingming Yang1, Weihong Chai1 and Yingfeng Zhang1 1 Northwestern Polytechnical University, School of Mechanical Engineering, China Introduction: Hydroxyapatite (HA) is one of the most popular bio-ceramics in biomedical tissue engineering applications due to its excellent biocompatibility[1] and not easy to cause inflammation and immune reaction[2]. 3DP can directly bond HA powder to fabricate artificial bone scaffolds on the basis of the individual patient bone parameters[3],[4]. Clarifying the interaction mechanism between binder and bioceramics power can improve the microstructure and mechanical properties of HA bone scaffold[5]-[7]. Therefore, we applied molecular dynamics (MD) methodology and physical experiments to study the bonding mechanism of bio-binders on the HA crystallographic planes for 3DP fabrication bone scaffolds. Materials and Methods: In this study, three kinds of popular bio-binders (polyvinylpyrrolidone (PVP), polyacrylamide (PAM), polyvinylalcohol (PVA)) and their interaction with HA surface systems were constructed and simulated (Fig.1), the cohesive energy densities of binders and the binding energies, pair correlation function (PCF) g(r), mechanical properties for various of binders/HA interaction models were analyzed. Furthermore, HA bone scaffold specimens with different glues were prepared by 3DP additive manufacturing according to the design scheme of simulations, their Young's modulus and compressive strength were tested by electronic universal testing machine. Finally, we analyzed the SEM pictures of transverse plane and fracture sections with different amplifications for HA bone scaffold specimens to explore the main reasons for differences in mechanical properties between simulation and experiment (Fig.2). Results and Discussion: The simulation results revealed that the relationship of the binding energies between binders and HA surface is consistent with the cohesive energy densities of binders, which is PAM/HA>PVA/HA>PVP/HA. The PCFs g(r) indicated that their interfacial interactions mainly attribute to the ionic bonds and hydrogen bonds which formed between the polar atoms, functional groups in binder polymer and the Ca, -OH in HA. The results of mechanical experiments verified the relationship of Young's modulus for three interaction models in simulation, which is PVA/HA>PAM/HA>PVP/HA. While the trend of compressive strength is PAM/HA>PVA/HA>PVP/HA, this is consistent with the binding energies of simulation. From the SEM pictures, the same phenomenon can be found in every sample. There were many small pores and incomplete infiltration points existing on the transverse plane and fracture sections of specimens, but HA pellets on the fracture sections of samples were not damaged (Such as the SEM pictures of PAM/HA bone scaffold in Fig.2). Thereby, the major reasons for differences in mechanical properties between simulation and experiment were found, the small space in the HA pellets and the incomplete infiltration of glue were the main factor influencing the mechanical properties of 3DP fabrication HA bone scaffolds. Conclusion: MD simulation is effective in analyzing the interfacial bonding behaviors of binder on HA surface. Their interfacial interactions mainly attribute to the ionic bonds and hydrogen bonds which formed between the polar atoms, functional groups in binder polymer and the Ca, -OH in HA. And the Young's modulus of bone scaffolds are limited by the Young's modulus of binders, the compressive strength is consistent with the viscosity of binder. Additionally, the major reasons for differences in mechanical properties between simulation and experiment were the bonding defect in the pellets and the incomplete infiltration of glue for 3DP fabrication HA bone scaffolds. These results provide useful information in choosing binder for 3DP fabrication bone scaffolds and understanding the interaction mechanism between binder and HA bioceramics power. the National Natural Science Foundation of China(Grant No. 51175432); the Doctor Special Science and Technological Funding of the China Ministry of Education; the Fundamental Research Funds for the Central Universities; the key Industrial Science and technology projects of Shaanxi; the Xinjiang Uygur Autonomous Region science and technology project

Study the bonding mechanism of binders on hydroxyapatite surface and mechanical properties for 3DP fabrication bone scaffolds

In 3DP fabricating artificial bone scaffolds process, the interaction mechanism between binder and bioceramics power determines the microstructure and macro mechanical properties of Hydroxyapatite (HA) bone scaffold. In this study, we applied Molecular Dynamics (MD) methods to investigating the bonding mechanism and essence of binders on the HA crystallographic planes for 3DP fabrication bone scaffolds. The cohesive energy densities of binders and the binding energies, PCFs g(r), mechanical properties of binder/HA interaction models were analyzed through the MD simulation. Additionally, we prepared the HA bone scaffold specimens with different glues by 3DP additive manufacturing, and tested their mechanical properties by the electronic universal testing machine. The simulation results revealed that the relationship of the binding energies between binders and HA surface is consistent with the cohesive energy densities of binders, which is PAM/HA>PVA/HA>PVP/HA. The PCFs g(r) indicated that their interfacial interactions mainly attribute to the ionic bonds and hydrogen bonds which formed between the polar atoms, functional groups in binder polymer and the Ca, –OH in HA. The results of mechanical experiments verified the relationship of Young׳s modulus for three interaction models in simulation, which is PVA/HA>PAM/HA>PVP/HA. But the trend of compressive strength is PAM/HA>PVA/HA>PVP/HA, this is consistent with the binding energies of simulation. Therefore, the Young׳s modulus of bone scaffolds are limited by the Young׳s modulus of binders, and the compressive strength is mainly decided by the viscosity of binder. Finally, the major reasons for differences in mechanical properties between simulation and experiment were found, the space among HA pellets and the incomplete infiltration of glue were the main reasons influencing the mechanical properties of 3DP fabrication HA bone scaffolds. These results provide useful information in choosing binder for 3DP fabrication bone scaffolds and understanding the interaction mechanism between binder and HA bioceramics power.

Alginate–Hydroxyapatite Bone Scaffolds with Isotropic or Anisotropic Pore Structure: Material Properties and Biological Behavior

AbstractAlginate/hydroxyapatite composites, with isotropic or anisotropic porosity, were developed using two different freezing methods. Morphological analysis highlighted the differences in their three‐dimensional network. Swelling and in vitro degradation studies revealed that both structures are highly hydrophilic and stable. Static compression tests showed that isotropic scaffolds possess higher modulus and toughness than anisotropic ones. Cyclic compression tests revealed that wet scaffolds are able to withstand high deformations with a peculiar shape‐recovery behaviour. In vitro biological tests showed that osteoblast‐like cells proliferate on both types of structures in a comparable manner.

The combination of mesenchymal stem cells and a bone scaffold in the treatment of vertebral body defects

Vertebral body defects represent one of the most common orthopedic challenges. In order to advance the transfer of stem cell therapies into orthopedic clinical practice, we performed this study to evaluate the safety and efficacy of a composite bioartificial graft based on a hydroxyapatite bone scaffold (CEM-OSTETIC(®)) combined with human mesenchymal stem cells (MSCs) in a rat model of vertebral body defects. Under general isoflurane anesthesia, a defect in the body of the L2 vertebra was prepared and left to heal spontaneously (group 1), implanted with scaffold material alone (group 2), or implanted with a scaffold together with 0.5 million MSCs (group 3) or 5 million MSCs (group 4). The rats were killed 8 weeks after surgery. Histological and histomorphometrical evaluation of the implant as well as micro-CT imaging of the vertebrae were performed. We observed a significant effect on the formation of new bone tissue in the defect in group 4 when compared to the other groups and a reduced inflammatory reaction in both groups receiving a scaffold and MSCs. We did not detect any substantial pathological changes or tumor formation after graft implantation. MSCs in combination with a hydroxyapatite scaffold improved the repair of a model bone defect and might represent a safe and effective alternative in the treatment of vertebral bone defects.

The mechanical properties and osteoconductivity of hydroxyapatite bone scaffolds with multi-scale porosity

The relative osteoconductivity and the change in the mechanical properties of hydroxyapatite (HA) scaffolds with multi-scale porosity were compared to scaffolds with a single pore size. Non-microporous (NMP) scaffolds contained only macroporosity (250-350 microm) and microporous (MP) scaffolds contained both macroporosity and microporosity (2-8 microm). Recombinant human bone morphogenetic protein-2 (rhBMP-2) was incorporated into all scaffolds via gelatin microspheres prior to implantation into the latissimus dorsi muscle of Yorkshire pigs. After 8 weeks, only the MP scaffolds contained bone. The result demonstrates the efficacy of the MP scaffolds as drug carriers. Implanted and as-fabricated scaffolds were compared using histology, microcomputed tomography, scanning electron microscopy, and compression testing. Implanted scaffolds exhibited a stress-strain response similar to that of cancellous bone with strengths between those of cancellous and cortical bone. The strength and stiffness of implanted NMP scaffolds decreased by 15% and 46%, respectively. Implanted MP scaffolds lost 30% of their strength and 31% of their stiffness. Bone arrested crack propagation effectively in MP scaffolds. The change in mechanical behavior is discussed and the study demonstrates the importance of scaffold microporosity on bone ingrowth and on the mechanical behavior of HA implant materials.

Effects of degradation and porosity on the load bearing properties of model hydroxyapatite bone scaffolds

Degradation of three types of model hydroxyapatite (HA) scaffolds was studied after in vitro degradation in a sodium acetate buffer (pH 4). Degradation was evaluated using compression testing, scanning electron microscopy (SEM), inductively coupled plasma (ICP) analysis, and weight measurements. Scaffolds were fabricated with a solid freeform fabrication (SFF) technique based on the robotic deposition of colloidal pastes. Scaffolds had a macrostructure resembling a lattice of rods. Scaffolds contained either macropores (270 or 680 microm in the x-y direction and 280 microm in the z-direction) and micropores (1-30-microm pores and pores <1 microm) or only macropores pores (270 microm in the x-y direction and 280 microm in the z-direction). A computer-aided design (CAD) program controlled the size and distribution of macropores; micropores were created by polymethylmethacrylate (PMMA) microsphere porogens (1-30-microm pore diameter) and controlled sintering (pores <1 microm). Percent weight loss of the scaffolds and calcium and phosphorus ion concentrations in solution increased as the degradation period increased for all scaffold types. After degradation, compressive strength and compressive modulus decreased significantly for those scaffolds with microporosity. For scaffolds without microporosity, the changes in strength and modulus after degradation were not statistically significant. The compressive strength of scaffolds without microporosity was significantly greater than the scaffolds with microporosity.

Development of hydroxyapatite bone scaffold for controlled drug release via poly(epsilon-caprolactone) and hydroxyapatite hybrid coatings.

A scaffold-coating design, the hydroxyapatite (HA) porous bone scaffold coated with poly(epsilon-)caprolactone (PCL) and HA powder hybrids, was developed for use as tissue-regeneration and controlled-release system. An antibiotic drug, tetracycline hydrochloride (TCH), was encapsulated within the hybrid coating layer through a dip-coating and solvent-casting method. Coating cycle and drug loading amount differed to control the level of drug-release rate. The HA scaffold framework, obtained by a polymeric foam reticulate method, exhibited a highly porous structure, with porosity and pore size of approximately 87% and 180 microm, respectively. The hybrid layer, consisting of PCL sheet and HA fine powders, was uniformly coated on the scaffold surface. The coating layer exhibited only PCL and HA phases and structures, revealing no chemical interaction among the coating components, as observed by X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) analyses. The coated-HA scaffolds showed an effective stress distribution behavior in response to an applied load, as confirmed by the compressive stress-strain curve. The mechanical properties of the coated scaffolds were improved highly with coatings; the compressive strength and elastic modulus of the cyclic coated scaffolds were approximately 3-4 times, and the energy absorption were approximately 8 times, higher than those without coating. These improvements were attributed mainly to the shielding of framework flaws by a flexible coating layer and partially to the thicker stems (porosity reduction). The dissolution of the coated scaffolds in a phosphate-buffered saline (PBS) solution increased with incubation time. The drug was released sharply within the initial several hours ( approximately 2 h), but the rate decreased further, showing a sustained release. The release amount was well controlled via coating-cycle and initial drug loading amount, suggesting the effectiveness of the coating-scaffold design as a drug-delivery system.