Polylactic Acid Hydroxyapatite Research Articles

Preparation and characterisation of a lamellar hydroxyapatite/polylactic acid composite

ABSTRACTIn this study, laminated hydroxyapatite/polylactic acid (HAp/PLA) composites were synthesized through solution intercalation method. The phase composition and micro morphology of the prepared HAp/PLA composites were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy, respectively. The obtained data revealed that intercalated and exfoliated structures were obtained by different HAp contents. Computed tomography result showed that the HAp lamellae distributed well in the PLA matrix and no air-bubble existed in the interface of HAp and PLA. Differential scanning calorimetry and mechanical performance test revealed that the thermal stability and tensile strength were all improved by intercalating of HAp lamellae. Moreover, the degradation experiment confirmed that the 10HAp/PLA showed the slowest degradation rate attributing to the molecular barrier effect of HAp lamellae. Besides that, MTT assay suggested that HAp/PLA composite exhibit excellent biocompatibility, indicating that it may become a promising material for biomedical applications.

Bioactive silver doped hydroxyapatite composite coatings on metal substrates: Synthesis and characterization

Antibacterial Ag-doped hydroxyapatite/polylactic acid(HA/PLA) composite coatings are rarely studied as implant coatings in recent years. Ag-doped hydroxyapatite (HA) powders were synthesized by chemical precipitation with different initial molar ratios of [Ag]/[Ca] (0(pure HA), 0.001, 0.003 and 0.005), and sintered in air at 800 °C. And then Ag-doped HA/PLA coatings were formed on stainless steel substrates by spin-coating technique for the first time. The obtained products were examined by the techniques of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), and X-ray photoelectron spectroscopy (XPS). The results showed that the doped Ag ions entered the crystal lattice of apatite successfully, but Ag3PO4 was also formed as the initial ratio of [Ag]/[Ca] increased. XPS suggested that some Ag3PO4 was then decomposed into metallic Ag in the high-temperature sintering process. Moreover, the addition of PLA could help form uniform composite coatings. The antibacterial activity of Ag-doped HA powders and Ag-doped HA/PLA composite coatings was also tested and showed a significant antibacterial property (bactericidal efficiency in 24h over 85%) while having low content of Ag. The results indicated both Ag-doped powders and composite coatings would be potential antibacterial materials for future applications.

Simulation of interfacial structures and mechanical properties of hydroxyapatite-polylactic acid and Zn-doped hydroxyapatite-polylactic acid

Simulation of interfacial structures and mechanical properties of hydroxyapatite-polylactic acid and Zn-doped hydroxyapatite-polylactic acid

Three dimensional printed polylactic acid-hydroxyapatite composite scaffolds for prefabricating vascularized tissue engineered bone: An in vivo bioreactor model

The repair of large bone defects with complex geometries remains a major clinical challenge. Here, we explored the feasibility of fabricating polylactic acid-hydroxyapatite (PLA-HA) composite scaffolds. These scaffolds were constructed from vascularized tissue engineered bone using an in vivo bioreactor (IVB) strategy with three-dimensional printing technology. Specifically, a rabbit model was established to prefabricate vascularized tissue engineered bone in two groups. An experimental group (EG) was designed using a tibial periosteum capsule filled with 3D printed (3DP) PLA-HA composite scaffolds seeded with bone marrow stromal cells (BMSCs) and crossed with a vascular bundle. 3DP PLA-HA scaffolds were also combined with autologous BMSCs and transplanted to tibial periosteum without blood vessel as a control group (CG). After four and eight weeks, neovascularisation and bone tissues were analysed by studying related genes, micro-computed tomography (Micro-CT) and histological examinations between groups. The results showed that our method capably generated vascularized tissue engineered bone in vivo. Furthermore, we observed significant differences in neovascular and new viable bone formation in the two groups. In this study, we demonstrated the feasibility of generating large vascularized bone tissues in vivo with 3DP PLA-HA composite scaffolds.

3D printing of hydroxyapatite polymer-based composites for bone tissue engineering

Abstract Skeletal defects reconstruction, using custom-made substitutes, represents a valid solution to replacing lost and damaged anatomical bone structures, renew their original function, and at the same time, restore the original aesthetic aspect. Rapid prototyping (RP) techniques allow the construction of complex physical models based on 3D clinical images. However, RP machines usually work with synthetic polymers; therefore, producing custom-made scaffolds using a biocompatible material directly by RP is an exciting challenge. The aim of the present work is to investigate the potentiality of 3D printing as a manufacturing method to produce an osteogenic hydroxyapatite-polylactic acid bone graft substitute.

Spin-coating synthesis and characterization of Zn-doped hydroxyapatite/polylactic acid composite coatings

Abstract Zn-doped hydroxyapatite/polylactic acid (HA/PLA) composite coatings fabricated by spin-coating technique have rarely been studied by other researchers in recent years. In this study, Zn-doped hydroxyapatite (Zn-doped HA) powder were synthesized by chemical precipitation method, and then Zn-doped hydroxyapatite/polylactic acid (Zn-doped HA/PLA) composite coatings were coated on stainless steel substrates using a spin-coating technique for the first time. The effects of heat treatment in air at 600 °C on the composition and morphology of Zn-doped HA/PLA composite coatings with a series of molar ratios of zinc (0 mol%, 5 mol%, 10 mol%, 15 mol% and 20 mol%) were studied. The obtained samples were characterized by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The results showed that Zn 2 + ions had replaced the partial Ca 2 + ions and were doped into hydroxyapatite lattice successfully. The synthetic hydroxyapatite nanoparticles showed rod-like morphology, whereas the substitution of the Zn ions restrained the growth of Zn-doped HA crystal and decreased its size. The surface morphology of Zn-doped HA/PLA composite coatings after sintering at 600 °C for 1 h exhibited a uniform, porous structure with a thickness of 60 μm or so. The introduction of PLA in composite coatings could keep metal substrates from catalyzing the decomposition of HA caused by high temperature heat treatment.

Synthesis and characterization of Cerium-doped hydroxyapatite/polylactic acid composite coatings on metal substrates

Ce-doped hydroxyapatite/polylactic acid (HA/PLA) composites serving as implant coatings have rarely been studied by other researchers in recent years. This paper was focused to study the existence of Ce ions in structure, chemical composition and surface morphology of HA and its composite coatings. Ce-doped HA powders were synthesized by chemical precipitation method with different Ce molar fractions (0(pure HA), 0.5 mol%, 1 mol% and 2 mol%). And Ce-doped HA/PLA composite coatings were fabricated for the first time on stainless steel substrates by spin coating technique. The obtained samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) coupled with energy dispersive X-ray detector (EDX), thermo gravimetric-differential thermal analysis (TG-DTA) and X-ray photoelectron spectroscopy (XPS). The results showed that Ce ions were doped into the crystal lattice of apatite successfully. The (Ce + Ca)/P atomic ratios in the doped HA/PLA samples ranged from 1.614 to 1.673, which were very close to the theoretical value of 1.67 for the stoichiometric HA. The addition of PLA could keep metal substrates from catalyzing the decomposition of HA. TG-DTA analysis indicated that Ce-doped HA powder had high thermal stability, and the SEM micrographs revealed that the surface topography of Ce-doped HA/PLA composite coatings was uniform and dense when the Ce molar fraction was 2 mol%. XPS results indicated that the Ce ions doped in HA showed mixed valences of Ce3+ and Ce4+.

Independent effects of the chemical and microstructural surface properties of polymer/ceramic composites on proliferation and osteogenic differentiation of human MSCs

Within the general aim of finding affordable and sustainable regenerative solutions for damaged and diseased tissues and organs, significant efforts have been invested in developing synthetic alternatives to natural bone grafts, such as autografts. Calcium phosphate (CaP) ceramics are among widely used synthetic bone graft substitutes, but their mechanical properties and bone regenerative capacity are still outperformed by their natural counterparts. In order to improve the existing synthetic bone graft substitutes, it is imperative to understand the effects of their individual properties on a biological response, and to find a way to combine the desired properties into new, improved functional biomaterials. To this end, we studied the independent effects of the chemical composition and surface microstructure of a poly(lactic acid)/hydroxyapatite (PLA/HA) composite material on the proliferation and osteogenic differentiation of clinically relevant bone marrow-derived human mesenchymal stromal cells (hMSCs). While the molecular weight of the polymer and presence/absence of the ceramic phase were used as the chemical variables, a soft embossing technique was used to pattern the surfaces of all materials with either pits or pillars with identical microscale dimensions. The results indicated that, while cell morphology was affected by both the presence and availability of HA and by the surface microstructure, the effect of the latter parameter on cell proliferation was negligible. The osteogenic differentiation of hMSCs, and in particular the expression of bone morphogenetic protein 2 (BMP-2) and osteopontin (OP) were significantly enhanced when cells were cultured on the composite based on low-molecular-weight PLA, as compared to the high-molecular-weight PLA-based composite and the two pure polymers. The OP expression on the low-molecular-weight PLA-based composite was further enhanced when the surface was patterned with pits. Taken together, within this experimental set up, the individual effect of the chemistry, and in particular of the presence of CaP, was more pronounced than the individual effect of the surface microstructure, although their combined effects were, in some cases, synergistic. The approach presented here opens new routes to study the interactions of biomaterials with the biological environment in greater depths, which can serve as a starting point for developing biomaterials with improved bioactivity. Statement of SignificanceThe aim of the this study was to obtain insight into independent effects of the chemical composition and surface microstructure of a poly(lactic acid)/hydroxyapatite (PLA/HA) composite material on the morphology, proliferation and osteogenic differentiation of clinically relevant bone marrow-derived human mesenchymal stromal cells (hMSCs). While the need for synthetic alternatives for natural bone in bone regenerative strategies is rapidly increasing, the clinical performance of synthetic biomaterials needs to be further improved. To do this successfully, we believe that a better understanding of the relationship between a property of a material and a biological response is imperative. This study is a step forward in this direction, and we are therefore convinced that it will be of interest to the readers of Acta Biomaterialia.

Preparation of phylloquinone-loaded poly(lactic acid)/hydroxyapatite core–shell particles and their drug release behavior

Poly(lactic acid)/hydroxyapatite (PLA/HAp) core–shell particles loaded with hydrophobic drugs were fabricated through a modified surfactant-free emulsification method. The core–shell particles are expected to encapsulate hydrophobic drugs, whose clinical use is often hampered because of their poor water solubility. In this study, phylloquinone, a drug that mediates the gamma carboxylation of glutamyl residues, was used as a model hydrophobic drug. Oil-in-water emulsions were prepared using an organic phase composed of dissolved PLA with various amounts of phylloquinone and an aqueous phase composed of calcium acetate and diammonium hydrogen phosphate. The obtained suspension exhibited a yellow color, indicating that the particles successfully incorporated phylloquinone. Scanning electron microscopy and X-ray diffraction analyses revealed these particles to be PLA/HAp core–shell composites loaded with phylloquinone, approximately 100–500nm in diameter. The particle diameters were affected by the amount of loaded phylloquinone; excess phylloquinone causes encapsulation failure. The drug release behavior of the phylloquinone-loaded PLA/HAp particles was examined via UV detection. The phylloquinone release profile showed a sustained release from the PLA/HAp core–shell particles over a ten days period.

Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model

We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 μm and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, β-tricalcium phosphate (β-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the biocompatibility, bone repairing capacity and degradation in three different bone substitute materials were estimated using a critical-size rat calvarial defect model in vivo. The defects were evaluated by micro-computed tomography and histological analysis at four and eight weeks after surgery, respectively. The results showed that each of the studied scaffolds had its own specific merits and drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good biocompatibility and stimulated BMSC cell proliferation and differentiation to osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds had good osteogenic capability and biodegradation activity with no difference in inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential applications in bone tissue engineering and may be used as graft substitutes in reconstructive surgery.

Preparation and characterization of hydroxyapatite-polylactic acid HA-PLA composite film

Preparation and characterization of hydroxyapatite-polylactic acid HA-PLA composite film

Development and dissolution studies of bisphosphonate (clodronate)-containing hydroxyapatite-polylactic acid biocomposites for slow drug delivery.

An increase in clinical demand on the controlled release of bisphosphonates (BPs) due to complications associated with systemic administration, has been the current driving force on the development of BP drug-release systems. Bisphosphonates have the ability to bind to divalent metal ions, such as Ca2+ , in bone mineral and prevent bone resorption by influencing the apoptosis of osteoclasts. Localized delivery using biodegradable materials, such as polylactic acid (PLA) and hydroxyapatite (HAp), which are ideal in this approach, have been used in this study to investigate the dissolution of clodronate (non-nitrogen-containing bisphosphonate) in a new release system. The effects of coral structure-derived HAp and the release kinetics of the composites were evaluated. The release kinetics of clodronate from PLA-BP and PLA-HAp-BP systems seemed to follow the power law model described by Korsmeyer-Peppas. Drug release was quantified by 31 P-NMR with detection and quantification limits of 9.2 and 30.7 mM, respectively. The results suggest that these biocomposite systems could be tuned to release clodronate for both relatively short and prolonged period of time. In addition to drug delivery, the degradation of HAp supplies both Ca2+ and phosphate ions that can help in bone mineralization. Copyright © 2015 John Wiley & Sons, Ltd.

Fabrication of poly (lactic acid)/hydroxyapatite (PLA/HAp) porous nanocomposite for bone regeneration

In this study, a poly (lactic acid)/hydroxyapatite (PLA/HAp) porous nanocomposite was fabricated by melt mixing method. Polyethylene oxide (PEO) was added into the nanocomposite to improve compatibility of HAp in the PLA matrix. A porous structure of the nanocomposite was created by using a salt (NaCl) which leaches in water. The influence of HAp's weight, compatibiliser content of porous agent on morphology and mechanical properties of PLA/HAp nanocomposite was investigated by SEM and tensile testing method. The obtained results indicated that the nanocomposite containing 20 wt% HAp, 5 wt% PEO, and an amount of NaCl in proportion with PLA weight (1 : 1) had good mechanical properties with a promising Young's modulus close to the one of cancellous bone (530 MPa) as well as a high porosity. The invitro tests of nanocomposite in simulated body fluids (SBF) were carried out and then pH of SBF solution, variation of material mass (Δm), morphology and phase structure of the nanocomposite were also estimated. The results showed that pH decreased, and Δm had positive or negative values depending on composition and surface of material formed by HAp crystals and the hydrolysis of PLA during immersion time.

Macroporous and nanometre scale fibrous PLA and PLA–HA composite scaffolds fabricated by a bio safe strategy

The present study deals with the design, fabrication and characterization of porous scaffolds for tissue engineering made of polylactic acid (PLA) and PLA containing hydroxyapatite (HA) nanoparticles. The main novelty relies on the fact that the fabrication of the scaffolds has been achieved avoiding totally the use of toxic chemicals. In particular, the scaffolds are obtained by combining both thermal induced phase separation (TIPS) using ethyl lactate (EL) solutions and supercritical CO2 (scCO2) drying processes. Furthermore, gelatin particles have been used as a leachable porogen and combined with the previous processes to improve the control of the pore structure features of the scaffolds. The results show that the developed technique allows for the fabrication of porous PLA scaffolds with HA concentrations up to 30 wt%. Furthermore, these scaffolds are characterized by an overall porosity as high as 98% and a double scale pore structure. In particular, the appropriate control of the TIPS process and the scCO2 drying allowed for the development of nanoscale fibrous PLA and PLA–HA structures starting from PLA/EL solutions. Concomitantly, the proper selection of the size range of gelatin particles as well as their spatial distribution in the mixture allowed imprinting an interconnected network of large pores inside the scaffolds.

Treatment of rabbit femoral head necrosis with polylactic acid/hydroxyapatite porous scaffold combined with rabbit bone marrow mesenchymal stem cells transfected by vascular endothelial growth factor

Objective To observe the curative effectiveness of implanting the polylactic acid/hydroxyapatite (PLA/HA) porous scaffold combined with rabbit bone marrow mesenchymal stem cells (BMSCs) transfected by plasmid pcDNA3.1-VEGF165 into the rabbit femoral head necrosis model.Methods The expression of vascular endothelial growth factor was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR) after rabbit BMSCs were transfected with pcDNA3.1-VEGF165 plasmid.Four groups were created:pcDNA3.1-VEGF165 plasmid transfection with scaffold group,blank vector transfection with scaffold group,simple scaffold group,and untreated group.Porous scaffolds were implanted into the femoral head.Micro-CT and histological evaluations were performed to observe the rabbit femoral head 8 and 12 weeks after operation.X-ray photography was performed after 12 weeks.Results VEGF expression level was significantly higher in pcDNA3.1-VEGF165 transfection group than other groups.Micro-CT and X-ray showed new bone formation and small blood vessels around the necrotic trabeculae.Femoral head deformation,thin subchondral bone,trabecular bone fracture and non-uniform bone mineral density were shown in other groups.Conclusion Plasmid pcDNA3.1-VEGF165 transfection of rabbit BMSCs with the PLA/HA porous scaffold could induce the formation of blood vessels and bone in rabbit femoral head. Key words: Femoral head necrosis; Vascular endothelial growth factor; Gene transfection; Mesenchymal stem cell

Structural Changes in Poly(lactic acid)/Hydroxyapatite Nanocomposites by Gamma Irradiation

Poly (lactic acid)/hydroxyapatite (PLA/HAP) nanocomposites were made via solution casting method and subjected to gamma irradiation at doses of 30 and 50 kGy. FTIR spectra of the nanocomposites displayed structural changes in the crystalline phase of PLA upon irradiation. The PLA/HAP nanocomposites of 6 and 10 pph HAP irradiated at 30 kGy showed higher tensile strengths. This was attributed to radiation-induced crystallinity that verified by DSC crystallinity measurements. Using triallyl isocyanurate (TAIC) as a multifunctional monomer promoted radiation-induced crosslinking reactions in PLA that was manifested by improvements in the tensile strength of the nanocomposites. Optimum values for TAIC, irradiation dose and HAP content were found as 1 pph, 30 kGy and 10 pph respectively. Raising the irradiation dose from 30 to 50 kGy prompted chain scission reactions that had adverse effects on tensile properties.

Study on Artificial Bone Scaffolds with Control Release of Drugs by Low-Temperature Rapid Prototyping Technology

A kind of PLGA microspheres was prepared with bovine serum albumin (BSA) as the model drug and poly (lactide-co-glycolide) as the matrix. The polylactic acid/hydroxyapatite (PLA/HA) scaffold was manufactured through 3D printing technology. Then the PLGA microspheres were composited in the scaffold. It was also explored about the feasibility of skeletal scaffolds loaded with bone growth factor. The BSA loading PLGA microspheres were prepared by W/O/W method and the scaffolds were prepared by 3D-printing using PLA and HA as raw materials. The composite scaffold was fabricated by adsorbing the microspheres/ethanol suspension into scaffolds under negative pressure. The cell-adhesion ability, hydrophilicity, scaffold morphology, release properties and biocompatibility of the composite scaffold were characterized, respectively. The results show no burst release of BSA from the PLGA microspheres at beginning stage and sustained longer than 35 days. Drug-loading rate of microspheres was 0.64%. PLA/HA scaffold shows enhanced hydrophilicity as well as excellent cell compatibility and cell adhesion property. SEM images show PLGA microspheres were successfully absorbed in PLA/HA scaffold. MTT experiments of the composite scaffold show non cytotoxic and its cell relative proliferation rate is up to 88.37%. These studies show the feasibility of skeletal scaffolds loaded with bone growth factor. Through low-temperature rapid prototyping technology, the long-effective bioactive bone scaffold can be prepared and have a well application prospect.

Lead ion removal characteristics of poly(lactic acid)/hydroxyapatite composite foams prepared by supercritical CO2 process

We have prepared a series of poly(lactic acid)/hydroxyapatite (PLA/HAp) composite foams by a supercritical CO2 foaming process and investigated the lead ion (Pb2+) removal performances of the foam samples in batch aqueous solutions (foam sample of 5 g, aqueous solution of 500 ml, initial Pb2+ ion concentration of 275 mg/l, pH values of 2.0–6.0) at 25°C. It is characterized that the porosity of the foams decreases from 96.3% to 50.3% as the HAp content increases from 0 to 40 wt%, although all the foam samples exhibit well-developed open porous structures. The maximum capacity of Pb2+ ions removed by the composite foams increases from 81.2 to 140.5 mg/g with increasing the HAp content from 10 to 40 wt%, due to the increased adsorption sites of HAp for Pb2+ ions. However, the removal kinetic analysis based on the pseudo-second order model demonstrates that the Pb2+ ion removal rate is slightly faster for the composite foams with higher porosity (i.e., lower HAp content). The maximum Pb2+ ion removal capacity of a given composite foam increases from 20.2 to 140.5 mg/g with increasing the initial pH value from 2.0 to 5.0 but it decreases slightly to 111.7 mg/g at the initial pH value of 6.0. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers

Absorption and release of protein from hydroxyapatite-polylactic acid (HA-PLA) membranes

Objectives The aim of this study was to investigate the kinetics of protein interactions with a novel hydroxyapatite-polylactide (HA-PLA) composite membrane material. Methods Trilayer PLA and HA-PLA composite membranes reinforced with PLA fibres were used to absorb and release protein which was measured by a BioRad assay. The proteins used were fetal calf serum and bovine serum albumin. PLA and HA-PLA composite films were manufactured to test permeability. Results Maximal protein absorption was seen within 5 min of treating materials; a nearly 8-fold increase in total absorption was seen with HA-containing composites compared to those without HA. These also exhibited a more gradual and sustained release of protein for periods of up to 96 h, for example at 24 h protein concentrations released were 2.20 ± 2.80 and 0.49 ± 5.38 μg/ml for membranes with and without HA respectively. In addition low pressure and temperature used during production of membranes also allowed greater and more sustained protein release. HA-PLA composite films also showed marked increased permeability compared to plain PLA films, for example after 24 h PLA only films 3.64 ± 1.01 μg/ml, PLA film with 25% HA: 44.99 ± 35.61 μg/ml, PLA film with 75% HA: 153.12 ± 65.57 μg/ml. Conclusions The results demonstrate that these composite membranes rapidly absorb protein and that the absorbed protein is released slowly for periods of up to 96 h, dependent on constituents of the material and the manufacturing conditions. Incorporation of HA into these membranes was the key factor for improved protein kinetics and membrane permeability.