Structural and morphological study of pulsed laser deposited calcium phosphate bioceramic coatings: influence of deposition conditions, laser parameters, and target properties

Calcium phosphate (CaP) bioceramics, especially hydroxyapatite (HA), have been used as coatings on implants owing to their biocompatible properties. The commercial practice for applying HA coating, plasma spraying, has some disadvantages which limit the long-term stability of the implants. Pulsed laser deposition (PLD) is being investigated as an alternative technique. The purpose of this research was to systematically study the effect of various parameters of the PLD process on the properties of CaP coatings. In this study, three types of HA targets and two laser wavelengths were used to make six categories of coatings. Predominantly crystalline HA coatings were produced under all six categories at optimum conditions, although small amounts of minor phases sometimes were found. Sufficient coating/substrate bond strength was also obtained. A wide variety of coating morphologies was obtained, from rather dense and uniform to rough and porous. The important factors that affected the morphology included target properties, vacuum level, deposition temperature, and laser wavelength and energy density. PLD's ability to produce both amorphous and crystalline, and both smooth/dense and rough/porous coatings may be a unique advantage.     

Liquid-phase laser process for simple and area-specific calcium phosphate coating

Simple, mild, and area-specific calcium phosphate (CaP) coating techniques are useful for the production and surface modification of biomaterials. In this study, an area-specific CaP coating technique for polymer substrates was successfully developed using a liquid-phase laser process. In the proposed method, Nd-YAG laser light (355 nm, 30 Hz, and 1-3 W) irradiated an ethylene-vinyl alcohol copolymer (EVOH) substrate immersed in a supersaturated CaP solution for various periods of time (up to 30 min). The CaP-forming ability increased with an increase in the laser power and irradiation period. At the optimal laser power (3 W), a continuous CaP layer formed within 30 min on the laser-irradiated surface of the EVOH substrate. The formation of CaP was attributed to laser absorption by the EVOH substrate, which promoted the surface modification of EVOH and an increase in the temperature of the solution near the surface of the substrate. The resulting CaP coating showed better cell adhesion property than the naked EVOH substrate. The proposed CaP coating technique is simple (quick and single step) and area specific. Furthermore, the present process is carried out under mild conditions, that is, at normal pressures and temperatures in a safe aqueous medium. These are significant advantages of the proposed CaP coating technique. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2573-2580, 2012.     

Laser-induced crystallization of calcium phosphate coatings on polyethylene (PE)

Calcium phosphate (CaP) coatings are used for obtaining a desired biological response. Usually, CaP coatings on metallic substrates are crystallized by annealing at temperatures of at least 400-600 degrees C. For polymeric substrates, this annealing is not possible due to the low melting temperatures. In this work, we present a more suitable method for obtaining crystalline coatings on polymeric substrates, namely laser crystallization. We were successful in obtaining hydroxyapatite coatings on polyethylene. Because of the UV transmission characteristics of the CaP coatings, the use of a low wavelength (157 nm) F(2) laser was necessary for this. As a result of the laser treatment, the CaP coating broke up into islands. The cracks between the islands became larger and the surface became porous with increasing laser energy. The mechanism behind the formation of this morphology did not become clear. However, the fact that crystalline CaP coatings can be obtained on polymeric substrates in an easy way, possibly allows for the development of new products.     

Preparation and characterization of RF magnetron sputtered calcium pyrophosphate coatings

CaP ceramic has been widely used as coating on metals in orthopedics and oral dentistry. Variations in CaP composition can lead to different dissolution/precipitation behavior and may also affect the bone response. In the present study calcium pyrophosphate and hydroxylapatite coatings were successfully prepared by RF magnetron sputtering deposition. The phase composition, morphological properties, and the dissolution in SBF were characterized by using XRD, FTIR, EDS, SEM, and spectrophotometry. The results showed that all the sputtered coatings were amorphous and changed into a crystal structure after IR-radiation. The temperature for the crystallization of the amorphous coatings is lower for the hydroxylapatite coating (550 degrees C), compared to the calcium pyrophosphate coating (650 degrees C). All sputtered amorphous coatings were instable in SBF and dissolved partially within 4 wks of incubation. The heat-treated coatings appeared to be stable after incubation. These results showed that magnetron sputtering of calcium pyrophosphate coating is a promising method for forming a biocompatible ceramic coating.     

Analytical and mechanical testing of high velocity oxy-fuel thermal sprayed and plasma sprayed calcium phosphate coatings

Plasma spraying (PS) is the most frequently used coating technique for implants; however, in other industries a cheaper, more efficient process, high-velocity oxy-fuel thermal spraying (HVOF), is in use. This process provides higher purity, denser, more adherent coatings than plasma spraying. The primary objective of this work was to determine if the use of HVOF could improve the mechanical properties of calcium phosphate coatings. Previous studies have shown that HVOF calcium phosphate coatings are more crystalline than plasma sprayed coatings. In addition, because the coatings are exposed to more complex loading profiles in vivo than standard ASTM tensile tests provide, a secondary objective of this study was to determine the applicability of four-point bend testing for these coatings. Coatings produced by HVOF and PS were analyzed by profilometry, diffuse reflectance Fourier transform infrared spectroscopy, X-ray diffraction, four-point bend, and ASTM C633 tensile testing. HVOF coatings were found to have lower amorphous calcium phosphate content, higher roughness values, and lower ASTM C633 bond strengths than PS coatings; however, both coatings had similar crystal unit cell sizes, phases present (including hydroxyapatite, beta-tricalcium phosphate, and tetracalcium phosphate), and four-point bend bond strengths. Thus, the chemical, structural, and mechanical results of this study, in general, indicate that the use of HVOF to produce calcium phosphate coatings is equivalent to those produced by plasma spraying.     

Physical, chemical, and biological characterization of pulsed laser deposited and plasma sputtered hydroxyapatite thin films on titanium alloy

The physical, chemical, and biological properties of pulsed laser deposited (PLD) and plasma sputtered (PS) hydroxyapatite (HA) coatings were compared. Human osteoblast-like cell responses to these coatings in vitro were assayed for proliferation and phenotypic expression. PS coatings formed smooth and continuous thin films that followed the contours of the substrate surface. PLD coatings consisted of numerous spheroidal micro- and macroparticles. The crystallinity of all coatings was quantified by comparison with the HA target used for both the PS and PLD processes. The XRD and FTIR results indicated that unannealed PLD coatings deposited at room temperature had X-ray spectra consistent with an amorphous structure and were found to dissolve after only a few hours in saline solution. Annealing at 400 degrees C increased the crystallinity (87-98%), which resulted in improved stability and cell activity. The PS coatings showed greater chemical stability than the unannealed PLD coatings and contained an approximate 15% crystalline phase, increasing to 65% postannealing. Cell proliferation and alkaline phosphatase production were significantly higher on unannealed PS specimens than the other coating treatments. There may be benefits in engineering the presence of a minor percentage of a microcrystalline phase in an amorphous or nanometer scale polycrystalline HA structure.     

Electrostatic spray deposition (ESD) of calcium phosphate coatings, an in vitro study with osteoblast-like cells

Electrostatic spray deposition (ESD) is a recently developed technique to deposit a calcium phosphate (CaP) coating upon substrates. With this technique, an organic solvent containing calcium and phosphate is pumped through a nozzle. Between the nozzle and substrate a high voltage is applied. As a consequence, droplets coming out the nozzle disperse into a spray, and this spray is deposited upon the substrate. When the solvent has evaporated, a coating is formed on the substrate. ESD allows for a variation in coating composition and morphology. Titanium alloy (TiAl6V4) substrates were coated with a CaP layer using two different methods; radio frequency magnetron sputtering, and ESD. These surfaces were characterized with X-ray diffraction, Fourier transform infrared spectroscopy, an universal surface tester, scanning electron microscopy, and energy dispersive spectrometry. Subsequently, bone marrow cells were isolated from rat femora and cultured 1, 4, 8, 14 and 16 days. Cell proliferation, alkaline phosphatase activity, and osteocalcin concentration were assayed. RT-PCR was done for collagen type I and osteocalcin. SEM was also performed to observe cellular behaviour during culture. Two separate runs of the experiment were performed. In the first run, osteoblast-like cells on both CaP coatings showed similar results in all assays. In the second run, proliferation and osteogenic expression had increased on ESD coatings. On basis of these results, we conclude that the novel ESD coating behaved similar to, or even better than the known RF magnetron sputter coating. Thus, ESD could be a valid addition to already existing CaP coating processes.     

Osteoclastic resorption of calcium phosphate coatings applied with electrostatic spray deposition (ESD), in vitro

Calcium phosphate (CaP) coatings have been applied on titanium implants to improve the bioactivity in order to favor the initial bone healing response. Recently, a new technique has been developed to apply CaP coatings: electrostatic spray deposition (ESD). Although ESD-derived coatings have several benefits, it is not known whether they are degradable. This study was designed to examine the cell-mediated degradation of two ESD-derived coatings with different chemical compositions, that is, beta-tricalcium phosphate (beta-TCP) and carbonate apatite (CA). First, coatings were deposited and analyzed physiochemically. Subsequently, rat bone marrow-derived osteoclastlike cells were seeded on the coatings, and analyzed with osteoclast-specific markers, scanning electron microscopy, and transmission electron microscopy. Results showed that both coatings exhibited porous morphologies, with an average pore size of less than 1 microm (beta-TCP), or larger than 1 microm (CA). After heat treatment, both coatings were crystalline in structure. The Ca/P ratios were 1.4 to 1.5 for the beta-TCP coating, and 1.8 to 2.0 for the CA coating. After 8 and 12 days of culture, multinucleated osteoclastlike cells were observed on both coatings. The osteoclast phenotype was confirmed by tartrate resistant acid phosphatase (TRAP) staining, and immunostaining against the calcitonin receptor. Using scanning electron microscopy, numerous resorption lacunae were observed in both coatings. Finally, transmission electron microscopy of TRAP-positive cells confirmed the osteoclastlike aspect of the cells revealing multiple nuclei and a ruffled border. In conclusion, CaP coatings produced with the ESD process can be degraded by osteoclasts.     

Significance of calcium phosphate coatings for the enhancement of new bone osteogenesis – A review

A systematic analysis of results available from in vitro, in vivo and clinical trials on the effects of biocompatible calcium phosphate (CaP) coatings is presented. An overview of the most frequently used methods to prepare CaP-based coatings was conducted. Dense, homogeneous, highly adherent and biocompatible CaP or hybrid organic/inorganic CaP coatings with tailored properties can be deposited. It has been demonstrated that CaP coatings have a significant effect on the bone regeneration process. In vitro experiments using different cells (e.g. SaOS-2, human mesenchymal stem cells and osteoblast-like cells) have revealed that CaP coatings enhance cellular adhesion, proliferation and differentiation to promote bone regeneration. However, in vivo, the exact mechanism of osteogenesis in response to CaP coatings is unclear; indeed, there are conflicting reports of the effectiveness of CaP coatings, with results ranging from highly effective to no significant or even negative effects. This review therefore highlights progress in CaP coatings for orthopaedic implants and discusses the future research and use of these devices. Currently, an exciting area of research is in bioactive hybrid composite CaP-based coatings containing both inorganic (CaP coating) and organic (collagen, bone morphogenetic proteins, arginylglycylaspartic acid etc.) components with the aim of promoting tissue ingrowth and vascularization. Further investigations are necessary to reveal the relative influences of implant design, surgical procedure, and coating characteristics (thickness, structure, topography, porosity, wettability etc.) on the long-term clinical effects of hybrid CaP coatings. In addition to commercially available plasma spraying, other effective routes for the fabrication of hybrid CaP coatings for clinical use still need to be determined and current progress is discussed.     

A review on calcium phosphate coatings produced using a sputtering process--an alternative to plasma spraying

New promising techniques for depositing hydroxyapatite (HA) and calcium phosphate (CaP) coatings on medical devices are continuously being investigated. Given the vast number of experimental deposition process currently available, this review will focus only on CaP and/or HA coatings produced using the sputtering process. This review will discuss the characterization of sputtered CaP coatings before and after post-deposition treatments and tissue responses to some of the characterized coating surfaces. From the studies observed in the literature, current research on sputtered CaP coatings has shown some promises that may eliminate some of the problems associated with the plasma-spraying process. It has been generally accepted that sputtered HA and CaP coatings improve bone strength and initial osseointegration rate. However, optimal coating properties required to achieve maximal bone response are yet to be reported. As such, the use of well-characterized sputtered CaP and/or HA surfaces in the evaluation of biological responses should be well documented to avoid controversial results. In addition, future investigations of the sputtering process should include clinical trials, to continue the understanding of bone responses to coated-implant surfaces of different properties, and the possibility of coupling sputtered HA and CaP coatings with growth factors.     

Influence of coating strain on calcium phosphate thin-film dissolution.

The success of calcium phosphate (CaP) coatings used to accelerate initial bone growth onto dental implants can vary depending on the CaP phases present in the coating. In this study, the effect of CaP coating crystal structure and morphology on dissolution rates was investigated. RF magnetron-sputtered CaP coatings (NTC) were compared to a less strained coating (HTC) obtained from heat treatment of sputtered samples at 550 degrees C. Coating strain differences were apparent in XRD spectra where hydroxyapatite-like planes shifted by 0.5 degrees 2theta and 0.05 degrees 2theta for the NTC and HTC coatings, respectively. HTC XRD peak widths were broader than NTC peak widths, indicating smaller crystals or grain sizes. These differences in grain size were corroborated by imaging with scanning probe microscopy. NTC coatings dissolved at a 300% faster rate than HTC coatings. A major factor contributing to this kinetic effect was the level of strain in both coatings. These results suggest an alternate design for CaP coatings can be obtained through the manipulation of coating strain. Using this approach, delivery of different ionic gradients from CaP coatings to surrounding tissue environments can be obtained from surfaces having similar chemistries.     

Influence of precursor solution parameters on chemical properties of calcium phosphate coatings prepared using Electrostatic Spray Deposition (ESD)

A novel coating technique, referred to as Electrostatic Spray Deposition (ESD), was used to deposit calcium phosphate (CaP) coatings with a variety of chemical properties. The relationship between the composition of the precursor solutions and the crystal and molecular structure of the deposited coatings was investigated by means of X-ray diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FTIR) and Energy Dispersive Spectroscopy (EDS). It was shown that the relative Ca/P ratio in the precursor solution, the absolute precursor concentration, the acidity of the precursor solution and the type of Ca-precursor strongly influenced the chemical nature of the deposited CaP coatings. Various crystal phases and phase mixtures were obtained, such as carbonate apatite, beta-TCP, Mg-substituted whitlockite, monetite, beta/gamma-pyrophosphate, and calcite.It was shown that carbonate plays an essential role in the chemical mechanism of coating formation. Carbonate is formed due to a decomposition reaction of organic solvents. Depending on deposition conditions, carbonate anions (a) react with acidic phosphate groups, (b) are incorporated into apatitic calcium phosphate phases, and (c) react with excessive Ca(2+) cations in case of phosphate-deficient precursor solutions.     

Enzymatic pH control for biomimetic deposition of calcium phosphate coatings

The current study examines the enzymatic decomposition of urea into carbon dioxide and ammonia as a means to increase the pH during biomimetic deposition of calcium phospate (CaP) onto implant surfaces. The kinetics of the enzymatically induced pH increase were studied by monitoring pH, calcium concentration and conductivity of the aqueous solutions as a function of time, urease concentration and initial concentrations of calcium and phosphate ions. Cryogenic transmission electron microscopy was used to study the process of homogeneous CaP precipitation in solution, whereas CaP deposition on conventional acid-etched titanium and micropatterned polystyrene (PS) surfaces was studied using scanning electron microscopy. The data presented in this study confirm that the substrate–enzyme combination urea–urease offers strong control over the rate of pH increase by varying the concentrations of precursor salts and urease. Formation of biomimetic CaP coatings was shown to proceed via formation of ionic polymeric assemblies of prenucleation complexes. The process of deposition and corresponding coating morphology was strongly dependent on the concentration of calcium, phosphate and urease. Finally, it was shown that the substrate–enzyme combination urea–urease allowed for spatial distribution of CaP crystals along the grooves of micropatterned PS surfaces at low concentrations of calcium, phosphate and urease, stressing the sensitivity of the presented method.     

Effect of post-deposition heating temperature and the presence of water vapor during heat treatment on crystallinity of calcium phosphate coatings

In this study, radiofrequency sputtered calcium phosphate (CaP) coatings were evaluated after 1 h post-deposition heat treatment at either 350°C, 400°C, 450°C, 500°C or 600°C in the presence or absence of water vapor. X-ray diffraction analyses indicated the as-sputtered coatings to be amorphous. With different post-deposition heat treatments used, in this study, crystallinity of CaP coatings was observed to be in the range of 0–68%. The 400°C and 450°C heat-treated CaP coatings in the absence of water vapor were poorly crystalline, exhibiting a crystallinity of 2±1%. In comparison to heat treatments at 450°C in the absence of water vapor, the presence of water vapor at 450°C heat treatment resulted in a significant increase in coating crystallinity. However, this effect was not observed at higher temperatures. A coating crystallinity of 60–68% was observed for coatings heat treated at 450°C in the presence of water vapor, and at 500°C and 600°C in the presence or absence of water vapor. In addition, increases in the degree of coating crystallinity were observed to be consistent with the increasing number of PO₄ peaks observed as a result of different post-deposition heat treatments. It was concluded that the presence of water vapor at 450°C post-deposition heat treatment significantly affect the crystallinity of CaP coatings, whereas an increase to temperature higher than 450°C and in the presence of water vapor has no significant effect on crystallinity.     

Microstructure and biological properties of micro-arc oxidation coatings on ZK60 magnesium alloy

Ceramic coatings were prepared on ZK60 magnesium alloy in electrolyte with different concentration ratio of calcium and phosphorus (Ca/P) by micro-arc oxidation (MAO) technique at constant voltage. The microstructure, phase composition, elemental distribution, corrosion resistance, and adhesion of the coatings were investigated by scanning electron microscope (SEM), X-ray diffractometer (XRD), energy-dispersive X-ray spectrometry (EDS), electrochemical workstation, and scratch spectrometer, respectively. The coating biocompatibility was evaluated by in vitro cytotoxicity tests and systemic toxicity tests, and the bioactivity and degradability were evaluated by simulation body fluid (SBF) immersion tests. SEM shows that pores with different shapes distribute all over the coating surface. The adhesion and thickness of the coatings increases with increasing Ca/P ratio of electrolyte. The in vitro cytotoxicity tests and systemic toxicity texts demonstrate that the coatings have no toxicity to cell and living animal, which show that the coatings have excellent biocompatibility. XRD analysis shows that bioactive calciumphosphate (CaP) phases such as hydroxyapatite (HA, Ca(10)(PO(4))(6)(OH)(2)) and calcium pyrophosphate (CPP, Ca(2)P(2)O(7)) are induced in the immersed coatings, indicating that the MAO coatings have excellent bioactivity.     

Bond strength of plasma-sprayed hydroxyapatite/Ti composite coatings

One of the most important clinical applications of hydroxyapatite (HA) is as a coating on metal implants, especially plasma-sprayed HA coating applied on Ti alloy substrate. However, the poor bonding strength between HA and Ti alloy has been of concern to orthopedists. In this paper, an attempt has been made to enhance the bonding strength of HA coating by forming a composite coating with Ti. The bioactivity of the coating has also been studied. HA/Ti composite coatings were prepared via atmospheric plasma spraying on Ti-6Al-4V alloy substrates. The bond strength evaluation of HA/Ti composite coatings was performed according to ASTM C-633 test method. X-ray diffractometer and scanning electron microscopy were applied to identify the phases and the morphologies of the coatings. The bioactivity of HA/Ti composite coating was qualified by immersion of coating in simulated body fluid (SBF). The obtained results revealed that the addition of Ti to HA improved the bonding strength of coating significantly. In the SBF test, the coating surface was covered by carbonate-apatite, which was testified by X-ray photoelectron spectroscope, indicating good bioactivity for HA/Ti composite coating. The bioactivity of the coating has not been reduced by the addition of Ti.     

On the feasibility of phosphate glass and hydroxyapatite engineered coating on titanium

In this report, bioactive calcium phosphate (CaP) coatings were produced on titanium (Ti) by using phosphate-based glass (P-glass) and hydroxyapatite (HA), and their feasibility for hard tissue applications was addressed in vitro. P-glass and HA composite slurries were coated on Ti under mild heat treatment conditions to form a porous thick layer, and then the micropores were filled in with an HA sol-gel precursor to produce a dense layer. The resultant coating product was composed of HA and calcium phosphate glass ceramics, such as tricalcium phosphate (TCP) and calcium pyrophosphate (CPP). The coating layer had a thickness of approximately 30-40 microm and adhered to the Ti substrate tightly. The adhesion strength of the coating layer on Ti was as high as 30-33 MPa. The human osteoblastic cells cultured on the coatings produced by the combined method attached and proliferated favorably. Moreover, the cells on the coatings expressed significantly higher alkaline phosphatase activity than those on pure Ti, suggesting the stimulation of the osteoblastic activity on the coatings. On the basis of these observations, the engineered CaP coating layer is considered to be potentially applicable as a hard tissue-coating system on Ti-based implants.     

Mechanical stability of two-step chemically deposited hydroxyapatite coating on Ti substrate: effects of various surface pretreatments

The success of implants in orthopaedic and dental load-bearing applications crucially depends on the initial biological fixation of implants in surrounding bone tissues. Using hydroxyapatite (HA) coating on Ti implant as carrier for bone morphogenetic proteins (BMPs) may promote the osteointegration of implants; therefore, reduce the risk of implant failure. The goal of this study was to develop an HA coating method in conditions allowing the incorporation of protein-based drugs into the coating materials, while achieving a mechanical stable coating on Ti implant. HA coatings were deposited on six different groups of Ti surfaces: control (no pretreatment), pretreated with alkali, acid, heat at 800°C, grit blasted with Al?O?, and grit blasted followed by heat treatment. HA coating was prepared using a two-step procedure. First step was the chemical deposition of a monetite coating on Ti substrate in acidic condition at 75°C and the second step was the hydrolysis of the monetite coating to HA. Coatings were characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). The roughness of substrates and coatings was measured using profilometry technique. The mechanical stability of the coatings deposited on the pretreated substrates was assessed using scratch test. The coatings deposited on the grit-blasted Ti surface demonstrated superior adhesive properties with critical shearing stress 131.6 ± 0.2 MPa.     

Initial deposition of calcium phosphate ceramic on polyethylene and polydimethylsiloxane by rf magnetron sputtering deposition: the interface chemistry

Calcium phosphate (CaP) coatings are well known for their bioactive nature. CaP coated polymeric materials can be used as implant material. For this, a strong adhesion between the coating and substrate is necessary. Because the chemical structure of the interface plays an important role in the coating adhesion, we studied the interface between CaP and the polymers polyethylene (PE) and polydimethylsiloxane (PDMS/silicone rubber). Both untreated and plasma pretreated polymers were used. On PE, a low Ca/P ratio nearby the interface and a high amount of C-O bonds were found on both untreated and plasma pretreated PE. This is the result of phosphate-like groups that are able to bind to the carbon of the PE. PDMS reacts towards the plasma pretreatment by losing CH(3) side groups. Compared to PE, a low amount of C-O bonds is found nearby the interface. Besides, a low Ca/P ratio is found nearby the interface. This is the result of phosphate groups that connect to Si atoms of the PDMS, thereby replacing the CH(3) side groups. The bombardment by negatively charged oxygen ions that are accelerated from the target during the deposition process makes the chemical interaction between the coating and the substrates possible.     

Preparation and evaluation of parathyroid hormone incorporated CaP coating via a biomimetic method

Parathyroid hormone (PTH) is a potent bone growth stimulator used for osteoporosis treatment. However, the inconvenience of daily administration and side effect of systemic exposure severely limit its use in clinical applications. Local, controlled delivery is a promising approach which can maintain therapeutic concentration locally for a long period. In this study, PTH was incorporated into a biomimetic calcium phosphate (CaP) coating via a coprecipitation process in a modified simulated body fluid (m-SBF). It was found that PTH was successfully incorporated into biomimetic CaP coating on titanium surface with a high incorporation efficiency. The incorporation of PTH into coatings had significantly changed the coating morphology, but the composition of the coating remained unchanged. Localized release of PTH had occurred in vitro, and was accompanied with partial dissolution of CaP coatings. Cell culture study demonstrated that the PTH released from CaP coatings fully retained its bioactivity. It had improved substantially MC3T3-E1 cell proliferation but slightly delayed the expression of alkaline phosphatase (ALP) of the cells. In summary, our results have shown that CaP coatings incorporated with PTH may be a promising approach for osteoporosis and other bone-related disease treatment in the future.