Biomineralized hyaluronic acid/poly(vinylphosphonic acid) hydrogel for bone tissue regeneration

Novel biomineralized hydrogels composed of hyaluronic acid (HA) and vinyl phosphonic acid (VPAc) were designed with the aim of developing a biomimetic hydrogel system to improve bone regeneration by local delivery of a protein drug including bone morphogenetic proteins. We synthesized crosslinked hydrogels composed of methacrylated HA and poly(VPAc) [P(VPAc)], which serves as a binding site for calcium ions during the mineralization process. The HA/P(VPAc) hydrogels were biomineralized by a urea‐mediation method to create functional polymer hydrogels that can deliver the protein drug and mimic the bone extracellular matrix. The water content of the hydrogels was influenced by the HA/P(VPAc) composition, crosslinking density, biomineralization, and ionic strength of the swelling media. All HA/P(VPAc) hydrogels maintained more than 84% water content. Enzymatic degradation of HA/P(VPAc) hydrogels was dependent on the concentration of hyaluronidase and the crosslinking density of the polymer network within the hydrogel. In addition, the release behavior of bovine serum albumin from the HA/PVPAc hydrogels was mainly influenced by the drug loading content, water content, and biomineralization of the hydrogels. In a cytotoxicity study, the HA/P(VPAc) and biomineralized HA/P(VPAc) hydrogels did not significantly affect cell viability. These results suggest that biomineralized HA/P(VPAc) hydrogels can be tailored to create a biomimetic hydrogel system that promotes bone tissue repair and regeneration by local delivery of protein drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41194.     

Morphology,wettability, and mechanical properties of polycaprolactone/hydroxyapatite composite scaffolds with interconnected pore structures fabricated by a mini‐deposition system

A new mini‐deposition system (MDS) was developed to fabricate scaffolds with interconnected pore structures and anatomical geometry for bone tissue engineering. Polycaprolactone/hydroxyapatite (PCL/HA) composites with varying hydroxyapatite (HA) content were adopted to manufacture scaffolds by using MDS with a porosity of 54.6%, a pore size of 716 μm in the x‐y plane, and 116 μm in the z direction. The water uptake ratio and compressive modulus of PCL/HA composite scaffold increase from 8 to 39% and from 26.5 to 49.8 MPa, respectively, as the HA content increases from 0 to 40%. PCL/HA composite scaffolds have better wettability and mechanical properties than pure PCL scaffold. A PCL/HA composite scaffold for mandible bone repair was successfully fabricated with both interconnected pore structures and anatomical shape to demonstrate the versatility of MDS. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers     

Surface‐engineered hydroxyapatite nanocrystal/ poly(ε‐caprolactone) hybrid scaffolds for bone tissue engineering

To achieve novel polymer/bioceramic composite scaffolds for use in materials for bone tissue engineering, we prepared organic/inorganic hybrid scaffolds composed of biodegradable poly(ε‐caprolactone) (PCL) and hydroxyapatite (HA), which has excellent biocompatibility with hard tissues and high osteoconductivity and bioactivity. To improve the interactions between the scaffolds and osteoblasts, we focused on surface‐engineered, porous HA/PCL scaffolds that had HA molecules on their surfaces and within them because of the biochemical affinity between the biotin and avidin molecules. The surface modification of HA nanocrystals was performed with two different methods. Using Fourier transform infrared, X‐ray diffraction, and thermogravimetric analysis measurements, we found that surface‐modified HA nanocrystals prepared with an ethylene glycol mediated coupling method showed a higher degree of coupling (%) than those prepared via a direct coupling method. HA/PCL hybrid scaffolds with a well‐controlled porous architecture were fabricated with a gas‐blowing/particle‐leaching process. All HA/PCL scaffold samples exhibited approximately 80–85% porosity. As the HA concentration within the HA/PCL scaffolds increased, the porosity of the HA/PCL scaffolds gradually decreased. The homogeneous immobilization of biotin‐conjugated HA nanocrystals on a three‐dimensional, porous scaffold was observed with confocal microscopy. According to an in vitro cytotoxicity study, all scaffold samples exhibited greater than 80% cell viability, regardless of the HA/PCL composition or preparation method. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Bioactive and Biocompatible Macroporous Scaffolds with Tunable Performances Prepared Based on 3D Printing of the Pre‐Crosslinked Sodium Alginate/Hydroxyapatite Hydrogel Ink

Bioactive and biocompatible porous scaffold materials with adjustable pore structures and drug delivery capability are one of the key elements in bone tissue engineering. In this work, bioactive and biocompatible sodium alginate (SA)/hydroxyapatite (HAP) macroporous scaffolds are facilely and effectively fabricated based on 3D printing of the pre‐crosslinked SA/HAP hydrogels followed by further crosslinking to improve the mechanical properties of scaffolds. The pore structures and porosity (>80%) of the porous scaffolds can be readily tailored by varying the formation conditions. Furthermore, the in vitro biomineralization tests show that the bioactivity of the porous scaffolds is effectively enhanced by the addition of HAP nanoparticles into the scaffold matrix. Furthermore, the anti‐inflammatory drug curcumin is loaded into the porous scaffolds and the in vitro release study shows the sustainable drug release function of the porous scaffolds. Moreover, mouse bone mesenchymal stem cells (mBMSCs) are cultured on the porous scaffolds, and the results of the in vitro biocompatibility experiment show that the mBMSCs can be adhered well on the porous scaffolds. All of the results suggest that the bioactive and biocompatible SA/HAP porous scaffolds have great application potential in bone tissue engineering.     

Fabrication and in vitro investigation of nanohydroxyapatite,chitosan, poly(L‐lactic acid) ternary biocomposite

The nanohydroxyapatite/chitosan/poly(L ‐lactic acid) (HA/CS/PLLA) ternary biocomposites were prepared by blending the hydroxyapatite/chitosan (HA/CS) nanocomposites with poly(L ‐lactic acid) (PLLA) solution. Surface modification by grafting D ‐, L ‐lactic acid onto the HA/CS nanocomposites was designed to improve the bonding with PLLA. The FTIR and ¹³C‐NMR spectrum confirmed that the oligo(lactic acid) was successfully grafted onto the HA/CS nanocomposites, and the time‐dependent phase monitoring showed that the grafted copolymers were stable. The TEM morphology of the HA/CS/PLLA ternary nanocomposites showed that nano‐HA fibers were distributed homogeneously, compacted closely and wrapped tightly by the CS and PLLA matrix. The ternary biocomposites with the HA content of 60 and 67 wt % exhibited high compressive strength of about 160 MPa and suitable hydrophilicity. The in vitro tests exhibited that the ternary biocomposites have good biodegradability and bioactivity when immersed in SBF solutions. All the results suggested that the n‐HA/CS/PLLA ternary biocomposites are appropriate to application as bone substitute in bone tissue engineering. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation and release study of ibuprofen‐loaded porous matrices of a biodegradable poly(ester amide) derived from L‐alanine units

Scaffolds of a biodegradable poly(ester amide) constituted of L ‐alanine, sebacic acid, and 1,12‐dodecanediol units (abbreviated as PADAS) were prepared by the compression‐molding/particulate‐leaching method. The influence of the type, size, and percentage of salt on the scaffold porosity and morphology was evaluated. The thermal behavior and crystallinity were also studied for samples obtained under different processing conditions. PADAS scaffolds were not cytotoxic because they showed good cell viability and supported cell growth at a similar ratio to that observed for the biocompatible materials used as a reference. The use of PADAS scaffolds as a drug‐delivery system was also evaluated by the employment of ibuprofen, a drug with well known anti‐inflammatory effects. Different drug‐loading methods were considered, and their influence on the release in a Sörensen's medium was evaluated as well as the influence of the scaffold morphology. A sustained release of ibuprofen could be attained without the production of a negative effect on the cell viability. The release kinetics of samples loaded before melt processing was well described by the combined Higuchi/first‐order model. This allowed the estimation of the diffusion coefficients, which ranged between 3 × 10^?14 and 5 × 10^?13 m²/s. Samples loaded by immersion in ibuprofen solutions showed a rapid release that could be delayed by the addition of polycaprolactone to the immersion medium (i.e., the release rate decreased from 0.027 to 0.015 h^?1). © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.     

Microarchitectural and mechanical characterization of chitosan/hydroxyapatite/demineralized bone matrix composite scaffold

Porous degradable scaffolds are used extensively in bone tissue engineering. As well as material type, the architectural and mechanical characterizations of scaffolds are important to facilitate cell and tissue growth. Matrices composed of hydroxyapatite (HA), chitosan (CS) and demineralized bone matrix (DBM) may create an appropriate environment for the regeneration of bones. In this study, CS/HA/DBM scaffolds with sufficient structural integrity and high interconnected porosity were produced using different combinations of CS, HA and DBM. Both mechanical and biological properties of porous scaffolds were determined by local microarchitecture whose parameters were quantified based on micro computed tomography (Micro-CT) analysis. Within porosity range of 48–65%, the ranges of average compressive modulus and ultimate strength of the scaffolds were 3 ± 1–6 ± 1 kPa and 11 ± 2–24 ± 2 kPa, respectively. With the increase of HA concentration at the equal weight of DBM, the average trabecular thickness and trabecular separation increased and bone surface/volume ratio decreased, resulting in higher volume fraction and lower total porosity. In vitro, MC3T3-E1 preosteoblast cells were used to investigate cell attachment, spreading and proliferation on the scaffolds via hematoxyline and eosin (HE), scanning electron microscopy (SEM) and MTS assay. The results showed that MC3T3-E1 cells adhered to the surface of composite scaffolds, cell number increased with culture time. Cell viability increased with the HA particles decreased, changed little with the DBM increased. Consideration of the microarchitectural and mechanical characterization and biocompatibility of the scaffolds, 3:3:1.5 and 3:5:1.5 groups were believed to be the best in our study.     

Calcium ion modulates protein release from chitosan‐hyaluronic acid poly electrolyte gel

Polyelectrolyte complex (PEC) of chitosan (CH) and hyaluronic acid (HA) are widely used for skin, cartilage, and bone tissue engineering. However, no reports are seen on their response at high ionic media, like increased Ca²⁺ where they are likely to be exposed in the form of bone constructs and the influence of these ions on modulating the release of incorporated entities such as drugs and growth factors. Here, we prepared freeze dried scaffolds of PEC of CH and HA (CH‐HA) and characterized them by FTIR, TGA, SEM, and ESEM. FITC conjugated BSA, designated as FA, was incorporated into the PEC to study the release properties in response to Ca²⁺. The swellability of CH‐HA and the extent of drug release from the matrix, FA loaded CH‐HA was studied in deionised water and aqueous Na⁺ and Ca²⁺ solutions. Swelling and drug release were high for the matrix in aqueous Ca²⁺ whereas it was remarkably low in water and Na⁺. Drug released was found to increase with concentrations of Ca²⁺ (0.02–1.0M) indicating that CH‐HA is a promising matrix for Ca²⁺ responsive delivery of agents to accelerate healing of bone cracks, which is known to release high amount of Ca²⁺. POLYM. ENG. SCI., 55:2089–2097, 2015. © 2015 Society of Plastics Engineers     

Sustained release of dexamethasone from drug‐loading PLGA scaffolds with specific pore structure fabricated by supercritical CO2 foaming

Inducing differentiation of bone marrow stem cells to generate new bone tissue is highly desirable by controlling the release of some osteoinductive or osteoconductive factors from porous scaffolds. In this study, dexamethasone was selected as a representative of small molecule drugs and dexamethasone‐loading porous poly(lactide‐co‐glycolide) (PLGA) scaffolds were successfully fabricated by supercritical CO₂ foaming. Scanning electron microscopy images showed that scaffolds had rough and relatively interconnected pores facilitating cells adhesion and growth. Specially, dexamethasone which was incorporated into PLGA matrix in a molecularly dispersed state could serve as a nucleation agent to be helpful for the formation of interconnected pores. Dexamethasone‐loading porous PLGA scaffolds exhibited sustained release profile, and the delivery of dexamethasone from porous scaffolds could last for up to 2 months. The cumulative released amount of dexamethasone was relevant with drug loading capacity (1.66%–2.95%) and pore structure of scaffolds; while the release behavior was anomalous (non‐Fickian) transport by fitting with the simple exponential equation, which had a diffusional exponent n higher than 0.5. It is feasible to fabricate drug‐loading porous scaffolds by supercritical CO₂ foaming with specific pore structure and sustained release profile, which can be well applied in bone tissue engineering. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46207.     

Preparation and performance of hydroxyapatite/Ti porous biocomposite scaffolds

Hydroxyapatite/titanium (HA/Ti) porous biocomposite scaffolds were prepared via a powder metallurgical method using NH₄HCO₃ as the pore-forming agent. The scaffolds induced HA formation and showed high bioactivity, and their porosity and compressive strength could be regulated by changing the NH₄HCO₃ dosage. When the NH₄HCO₃ dosage was 40.0%, the porosity was 67.0 ± 0.8%, and compressive strength was 19.0 ± 0.6 MPa, indicating the corresponding scaffold was an ideal choice for spongy bone repair.     

β‐cyclodextrin‐conjugated hyaluronan hydrogel as a potential drug sustained delivery carrier for wound healing

In order to develop a potential drug sustained delivery carrier suitable for wound healing, a series of β‐cyclodextrin conjugated hyaluronan hydrogels (β‐CD‐HA) with adjustable crosslink densities were synthesized and characterized, meanwhile the delivery kinetics and mechanism of diclofenac as a model anti‐inflammatory drug from these hydrogels were investigated. By controlling the feeding molar ratio of β‐CD/HA, a β‐CD substitution degree of 4.65% was obtained by ¹H‐NMR analysis. The incorporation of β‐CD modification had little effect on the internal porous structure, water swelling ratio, and rheological property of HA hydrogel, which however were influenced by the crosslink density. Although the crosslink density had an influence on the drug loading and release profile by altering the water swelling property, the interaction between β‐CD and drug was the primary factor for the high loading capacity and long‐term sustained delivery of diclofenac. The semiempirical equation fit showed that the release of diclofenac from HA‐based hydrogels followed a pseudo‐Fickian diffusion mechanism. By the aid of β‐CD and controlled crosslink density, a β‐CD‐HA hydrogel with a diclofenac sustained delivery period of over 28 days and desirable physicochemical properties was achieved, which will be a promising drug sustained delivery carrier for wound healing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43072.     

Adsorption and drug release based on β‐cyclodextrin‐grafted hydroxyapatite composite

In this study, β‐cyclodextrin (β‐CD) was covalently grafted on hydroxyapatite (HA) using a coupling agent to improve the drug loading capacity and prolong the drug release. The binding of β‐CD on the HA surface was confirmed by Fourier transformation infrared spectroscopy, thermal gravimetric analysis, and X‐ray powder diffraction. The adsorption capacity of ofloxacin on β‐CD‐grafted hydroxyapatite (β‐CD‐g‐HA) composite was found to be 30 mg g^?1 at 37°C and 24 h. The adsorption process is spontaneous, given the negative values of free energy change. Compared with the release of ofloxacin loaded on HA, the release of ofloxacin loaded on β‐CD‐g‐HA was slowed down 28% and 21% in pH 2.0 and pH 7.4 buffer media at 2 h, respectively. Biocompatibility of β‐CD‐g‐HA was assessed by MTT assay, and the result showed that it had no cytotoxicity. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Fabrication,characterization and drug loading of pH‐dependent multi‐morpho‐ logical nanoparticles based on cellulose

This paper investigates the pH‐dependent micellization of (hydroxyethyl cellulose)‐graft‐poly(acrylic acid) (HEC‐graft‐PAA), the crosslinking of the pH‐induced nanoparticles and the drug loading of the crosslinked multi‐morphological nanoparticles. The hydrodynamic diameter (〈D_h〉) of the pH‐induced micelles was found dependent on both temperature and concentration in dynamic light scattering studies. After the crosslinking of PAA segments in the micelles, shape‐persistent nanoparticles were obtained, which exhibited multiple morphologies from nano‐cage to hollow sphere, and a homogeneous swollen microgel in neutral medium with an increase of the degree of crosslinking. To investigate the drug loading of these shape‐persistant nanoparticles, diminazene aceturate was chosen as a model drug. The loading efficiency and the drug release behavior against water and 0.1 mol L^?1 NaCl were studied using UV absorption spectroscopy. Copyright © 2007 Society of Chemical Industry     

Preparation and characterization of vancomycin releasing PHBV coated 45S5 Bioglass®-based glass–ceramic scaffolds for bone tissue engineering

Porous 45S5 Bioglass^®-based glass–ceramic scaffolds with high porosity (96%) and interconnected pore structure (average pore size 300 μm) were prepared by foam replication method. In order to improve the mechanical properties and to incorporate a drug release function, the scaffolds were coated with a drug loaded solution, consisting of PHBV and vancomycin. The mechanical properties of the scaffolds were significantly improved by the PHBV coating. The bioactivity of scaffolds upon immersion in SBF was maintained in PHBV coated scaffolds although the formation of hydroxyapatite was slightly retarded by the presence of the coating. The encapsulated drug in coated scaffolds was released in a sustained manner (99.9% in 6 days) as compared to the rapid release (99.5% in 3 days) of drug directly adsorbed on the uncoated scaffolds. The obtained drug loaded and bioactive composite scaffolds represent promising candidates for bone tissue engineering applications.     

Chitosan/gelatin porous bone scaffolds made by crosslinking treatment and freeze‐drying technology: Effects of crosslinking durations on the porous structure,compressive strength,and in vitro cytotoxicity

In this study, freezing was used to separate a solute (polymer) and solvent (deionized water). The polymer in the ice crystals was then crosslinked with solvents, and this diminished the linear pores to form a porous structure. Gelatin and chitosan were blended and frozen, after which crosslinking agents were added, and the whole was frozen again and then freeze‐dried to form chitosan/gelatin porous bone scaffolds. Stereomicroscopy, scanning electron microscopy, compressive strength testing, porosity testing, in vitro biocompatibility, and cytotoxicity were used to evaluate the properties of the bone scaffolds. The test results show that both crosslinking agents, glutaraldehyde (GA) and 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide, were able to form a porous structure. In addition, the compressive strength increased as a result of the increased crosslinking time. However, the porosity and cell viability were not correlated with the crosslinking times. The optimal porous and interconnected pore structure occurred when the bone scaffolds were crosslinked with GA for 20 min. It was proven that crosslinking the frozen polymers successfully resulted in a division of the linear pores, and this resulted in interconnected multiple pores and a compressively strong structure. The 48‐h cytotoxicity did not affect the cell viability. This study successfully produced chitosan/gelatin porous materials for biomaterials application. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41851.     

Injection‐molded porous hydroxyapatite/polyamide‐66 scaffold for bone repair and investigations on the experimental conditions

Hydroxyapatite/polyamide‐66 (HA/PA66) composite scaffolds were prepared using injection‐molding technique and also analyzed by means of scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, and mechanical testing. Compared with common methods to fabricate scaffolds, this process can fabricate composite scaffolds in a rapid and convenient manner by adjusting the experimental conditions of foaming agent and shot size. The interactions between PA66 and HA particles affect the crystallization behavior of PA66 and the pore structure of scaffolds. HA particles can increase the stiffness of composite scaffolds accompanied by the reduction of impact strength, pore size and porosity. The obtained 40 wt% HA/PA66 composite scaffolds with a pore size ranging from 100–500 μm and a porosity more than 65% can simultaneously meet the requirements of porous structure and mechanical performance. POLYM. ENG. SCI., 54:1003–1012, 2014. © 2013 Society of Plastics Engineers     

Influence of hydroxyapatite and BMP‐2 on bioactivity and bone tissue formation ability of electrospun PLLA nanofibers

An excellent bioactive scaffold material which could induce and promote new bone formation is essential in the bone repair field. In this study, the bioactive material hydroxyapatite (HA) and the bone morphogenetic protein‐2 (BMP‐2) were added to poly‐l‐lactic acid (PLLA) using the electrospinning method. Scanning electron microscopy investigations performed on four different fiber scaffolds, PLLA, PLLA/HA, PLLA/BMP‐2 and PLLA/HA/BMP‐2, revealed that the fibers of all scaffolds are closely interwoven, and the presence of large interconnected voids between the fibers, resulting in a three‐dimensional porous network structure that was similar to the structure of the extracellular matrix of healthy bones. In the MG63 cell culture growth experiments, the composite scaffold material PLLA/HA/BMP‐2 showed a higher bioactivity than the other three scaffold materials. The four scaffold materials were implanted in rabbits’ tibia for 30 and 90 days. The results of the animal experiments indicate that the capability of the PLLA/HA/BMP‐2 composite to induce and promote bone tissue formation was better compared with PLLA/HA or PLLA/BMP‐2, suggesting that PLLA combined with HA/BMP‐2 is a promising material for bone tissue repair. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42249.     

Effects of micro and nano β‐TCP fillers in freeze‐gelled chitosan scaffolds for bone tissue engineering

Tissue engineering holds an exciting promise in providing a long‐term cure to bone‐related defects and diseases. However, one of the most important prerequisites for bone tissue engineering is an ideal platform that can aid tissue genesis by having biomimetic, mechanostable, and cytocompatible characteristics. Chitosan (CS) was chosen as the base polymer to incorporate filler, namely beta‐tri calcium phosphate (β‐TCP). This research deals with a comparative study on the properties of CS scaffolds prepared using micro‐ and nano‐sized β‐TCP as filler by freeze gelation method. The scaffolds were characterized for their morphology, porosity, swelling, structural, chemical, biodegradation, and bioresorption properties. Rheological behavior of polymer and polymer‐ceramic composite suspensions were analyzed and all the suspensions with varying ratios of β‐TCP showed non‐Newtonian behavior with shear thinning property. Pore size, porosity of micro‐ and nano‐sized composite scaffolds are measured as 48–158 μm and 77% and 43–155 μm and 81%, respectively. The scaffolds containing nano β‐TCP possess higher compressive strength (～2.67 MPa) and slower degradation rate as compared to composites prepared with micro‐sized β‐TCP (～1.52 MPa). Bioresorbability, in vitro cell viability by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, proliferation by Alamar blue assay, cell interaction by scanning electron microscope, and florescence microscopy further validates the potentiality of freeze‐gelled CS/β‐TCP composite scaffolds for bone tissue engineering applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41025.     

Composite chitosan/poly(ethylene oxide) electrospun nanofibrous mats as novel wound dressing matrixes for the controlled release of drugs

The aim of this study was to develop novel biomedical electrospun nanofiber mats for controlled drug release, in particular to release a drug directly to an injury site to accelerate wound healing. Here, nanofibers of chitosan (CS), poly(ethylene oxide) (PEO), and a 90 : 10 composite blend, loaded with a fluoroquinolone antibiotic, such as ciprofloxacin hydrochloride (CipHCl) or moxifloxacin hydrochloride (Moxi), were successfully prepared by an electrospinning technique. The morphology of the electrospun nanofibers was investigated by scanning electron microscopy. The functional groups of the electrospun nanofibers before and after crosslinking were characterized by Fourier transform infrared spectroscopy. X‐ray diffraction results indicated an amorphous distribution of the drug inside the nanofiber blend. In vitro drug‐release evaluations showed that the crosslinking could control the rate and period of drug release in wound‐healing applications. The inhibition of bacterial growth for both Escherichia coli and Staphylococcus aureus were achieved on the CipHCl‐ and Moxi‐loaded nanofibers. In addition, both types of CS/PEO and drug‐containing CS/PEO nanofibers showed excellent cytocompatibility in the cytotoxicity assays. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42060.     

Biodegradable chitosan-based composites with dual functions acting as the bone scaffold and the inflammation inhibitor in the treatment of bone defects

A composite based on nano-hydroxyapatite (n-HA)/chitosan (CS) and loaded with ciprofloxacin (CIP) was prepared and its physicochemical properties, antibacterial properties, drug release ability, and bone regeneration ability were characterized. The physicochemical results indicated that the n-HA/CS composite exhibited about a 70/30 ratio of n-HA to CS, and the size of n-HA in the n-HA/CS composite was about 100?nm. According to the results of the antibacterial test, the materials loaded with CIP presented excellent antibacterial activity. In addition, the in vivo concentration of CIP far surpassed the minimum inhibitory concentration (0.25–2?µg?mL^?1). In vitro standard deviation-rats marrow mesenchymal stem cells (MSCs) tests, including cell counting kit-8 assay and scanning electron microscopy images of MSCs, revealed that both of the scaffolds could support MSCs proliferation and attachment. The in vivo results indicated that n-HA/CS-CIP could promote the formation of bone tissues and blood vessels, and displayed a better repair ability for bone defect than the control group of n-HA-CIP. The CS-based composite with dual functions has a good perspective which would justify further research.