Injectable, self-healing hydrogels based on gelatin, quaternized chitosan, and laponite as localized celecoxib delivery system for nucleus pulpous repair.

Utilization of injectable hydrogels stands as a paradigm of minimally invasive intervention in the context of intervertebral disc degeneration treatment. Restoration of nucleus pulposus (NP) function exerts a profound influence in alleviating back pain. This study introduces an innovative class of injectable shear-thinning hydrogels, founded on quaternized chitosan (QCS), gelatin (GEL), and laponite (LAP) with the capacity for sustained release of the anti-inflammatory drug, celecoxib (CLX). First, synthesis of Magnesium-Aluminum-Layered double hydroxide (LDH) was achieved through a co-precipitation methodology, as a carrier for celecoxib and a source of Mg ions. Intercalation of celecoxib within LDH layers (LDH-CLX) was verified through a battery of analytical techniques, including FTIR, XRD, SEM, EDAX, TGA and UV-visible spectroscopy confirmed a drug loading efficiency of 39.22 ± 0.09 % within LDH. Then, LDH-CLX was loaded in the optimal GEL-QCS-LAP hydrogel under physiological conditions. Release behavior (15 days profile), mechanical properties, swelling ratio, and degradation rate of the resulting composite were evaluated. A G* of 15-47 kPa was recorded for the hydrogel at 22-40 °C, indicating gel stability in this temperature range. Self-healing properties and injectability of the composite were proved by rheological measurements. Also, ex vivo injection into intervertebral disc of sheep, evidenced in situ forming and NP cavity filling behavior of the hydrogel. Support of GEL-QCS-LAP/LDH-CLX (containing mg2+ ions) for viability and proliferation (from ~94 % on day 1 to ~134 % on day 7) of NP cells proved using MTT assay, DAPI and Live/Dead assays. The hydrogel could significantly upregulate secretion of glycosaminoglycan (GAG, from 4.68 ± 0.1 to 27.54 ± 1.0 µg/ml), when LHD-CLX3% was loaded. We conclude that presence of mg2+ ion and celecoxib in the hydrogel can lead to creation of a suitable environment that encourages GAG secretion. In conclusion, the formulated hydrogel holds promise as a minimally invasive candidate for degenerative disc repair.

Gelatin/O-carboxymethyl chitosan injectable self-healing hydrogels for ibuprofen and naproxen dual release.

Recently, a significantly greater clinical benefit has been reported with a combination of glucosamine sulfate and nonsteroidal anti-inflammatory drugs (NSAIDs) compared to either treatment alone for the growing osteoarthritis (OA) disease. So, this study introduces hydrogels using O-carboxymethyl chitosan (O-CMC, structurally akin glucosamine glycan), and Gelatin type A (GA) in a 1:2 ratio with ß-glycerophosphate (ßGPh) at varying percentages (5 %, 12.5 %, and 15 %). We show that hydrogel properties, adaptable for drug delivery or tissue engineering, can be fine-tuned based on OCMC:ßGPh ratio. CMC/GA/ßGPh-12.5 exhibited a swelling rate of 189 %, compressive stress of 164 kPa, and compressive modulus of 3.4 kPa. The self-healing hydrogel also exhibited excellent injectability through a 21-gauge needle, requiring only 5 N of force. Ibuprofen and Naproxen release from CMC/GA/ßGPh-12.5 and CMC/GA/ßGPh-15 of designed dimensions (bi-layer structures of different diameter and height) were measured, and drug release kinetics were estimated using mathematical equations (MATLAB and polyfit program). CMC/GA/ßGPh-12.5 demonstrated significant antibacterial effects against E. coli and S. aureus, a high cell survival rate of 89 % against L929 fibroblasts, and strong cell adhesion, all indicating biocompatibility. These findings underscore potential of these hydrogels as promising candidates for treating inflammatory diseases such as osteoarthritis.

A Rapid Screening Platform for Simultaneous Evaluation of Biodegradation and Therapeutic Release of an Ocular Hydrogel.

This study attempts to address the challenge of accurately measuring the degradation of biodegradable hydrogels, which are frequently employed in drug delivery for controlled and sustained release. The traditional method utilizes a mass-loss approach, which is cumbersome and time consuming. The aim of this study was to develop an innovative screening platform using a millifluidic device coupled with automated image analysis to measure the degradation of Gelatin methacrylate (GelMA) and the subsequent release of an entrapped wetting agent, polyvinyl alcohol (PVA). Gel samples were placed within circular wells on a custom millifluidic chip and stained with a red dye for enhanced visualization. A camera module captured time-lapse images of the gels throughout their degradation. An image-analysis algorithm was used to translate the image data into degradation rates. Simultaneously, the eluate from the chip was collected to quantify the amount of GelMA degraded and PVA released at various time points. The visual method was validated by comparing it with the mass-loss approach (R = 0.91), as well as the amount of GelMA eluted (R = 0.97). The degradation of the GelMA gels was also facilitated with matrix metalloproteinases 9. Notably, as the gels degraded, there was an increase in the amount of PVA released. Overall, these results support the use of the screening platform to assess hydrogel degradation and the subsequent release of entrapped therapeutic compounds.

Conductive polymers for cardiac tissue engineering and regeneration.

Cardiovascular diseases, such as myocardial infarction, are considered a significant global burden and the leading cause of death. Given the inability of damaged cardiac tissue to self-repair, cell-based tissue engineering and regeneration may be the only viable option for restoring normal heart function. To maintain the normal excitation-contraction coupling function of cardiac tissue, uniform electronic and ionic conductance properties are required. To transport cells to damaged cardiac tissues, several techniques, including the incorporation of cells into conductive polymers (CPs) and biomaterials, have been utilized. Due to the complexity of cardiac tissues, the success of tissue engineering for the damaged heart is highly dependent on several variables, such as the cell source, growth factors, and scaffolds. In this review, we sought to provide a comprehensive overview of the electro CPs and biomaterials used in the engineering and regeneration of heart tissue.

Corneal sustained delivery of hyaluronic acid from nanofiber-containing ring-implanted contact lens.

Dry eye syndrome, as a persist corneal epithelial defect (PED), is an inconvenient ocular disorder that is generally treated by high-dosage, conventional eye drops. Addressing low efficacy and rather restricted bioavailability of the conventional eye drops, drug-eluting contact lenses (CLs) are widely used as alternatives in ophthalmic drug delivery applications. In the present study, a nanofiber-containing ring implant poly (vinyl alcohol) (PVA) hydrogel is designed as a carrier for hyaluronic acid (HA) delivery. hyaluronic acid is physically encapsulated in a nanofiber-containing ring-shaped hydrogel with a 2 mm width that is implanted in the final CLs hydrogel. The designed CL has 59% porosity, 275% swelling ratio and undergoes no weight loss at physiological conditions in14 days. In-vitro release studies were performed on the CLs with and without nanofibers. The results showed that nanofiber incorporation in the designed CL was highly influential in decreasing burst release and supported sustained release of HA over 14 days. In addition, nanofiber incorporation in the designed system strengthened the lens, and the young modulus of the PVA hydrogel increased from 6 to 10 kPa. Cell viability study also revealed no cell cytotoxicity and cell attachment. Overall, the study demonstrated the effective role of nanofibers in the physical strengthening of the CL. Also, the designed system holds promise as a potential candidate for HA delivery over an extended period for treating dry eye syndrome.

Dexamethasone loaded injectable, self-healing hydrogel microspheresbased on UPy-functionalized Gelatin/ZnHAp physical network promotes bone regeneration.

Biopolymer-based injectable hydrogels provide great potential as bone tissue engineering (BTE) scaffolds on account of biocompatibility, and pore interconnectivity that enables delivery of cells and/or signaling molecules for bone repair. Recently, Gelatin hydrogels based on H-bonds were considered in response to concerns around the chemical crosslinking agents. In this study, a self-healing gelatin hydrogel with remarkable compressive and self-healing properties was prepared via formation of quadruple hydrogen bonds between ureidopyrimidinon functional groups, which were substituted on NH2 groups of gelatin(GelUPy). Degree of substitution controls properties of the resulting hydrogel from a shape- memory hydrogel (100% substitution), to a hydrogel (about 80%), to this self-healing hydrogel (about 40%). We report a strategy that adopts an emulsion synthesis approach to delivery of dexamethasone and Ca/Zn ions from injectable self-healing GelUPy hydrogel (GelUPy-ZnHApUPy-DEX), to induce osteogenic differentiation of adipose-derived stem cells, in vitro, and enhance bone regeneration in a cranial bone defect in a rat model. We show that key properties of the composite hydrogels, including mechanical properties, and release behavior of DEX are a match to the requirements of BTE. Overall, our results demonstrate that this self-healing gelatin approach is a promising strategy to enhance bone regeneration through a minimally invasive procedure.

Impact of supramolecular interactions on delivery of dexamethasone from a physical network of gelatin/ZnHAp composite scaffold.

Synthesis of a supramolecular composite hydrogel, a novel class of physical and dynamic hydrogels, is reported. The hydrogel comprised gelatin (Gel), Zn-doped nano-hydroxyapatite (nZnHAp), and dexamethasone disodium phosphate (DEX). nZnHAp was functionalized with ureidopyrimidinone (UPy; quadruple hydrogen-bond-forming groups). The nHAp, nZnHAp, and nZnHApUPy were characterized by FTIR, EDX, SEM, and TGA analysis. Gelatin was also functionalized with UPy groups (GelUPy), and the nanocomposites were prepared in solution (GelUPy/nZnHApUPy). Dexamethasone was added to the composite hydrogels (15, 20, and 25 wt%), as an osteoinductive and anti-inflammation medicine (GelUPy/nZnHApUPy/DEX). The mechanical (in compression mode), rheological, and thermal properties of the GelUPy/nZnHApUPy/DEX were compared with those of GelUPy/nZnHAp/DEX. The GelUPy/nZnHApUPy/DEX series showed the maximum compressive modulus (about 841 KPa) for GelUPy/nZnHApUPy/DEX25% in the swollen state. DSC analysis indicated that Tg of the pure GelUPy decreased significantly upon composite preparation and drug loading from 160 °C for GelUPy, down to 107 °C for GelUPy/nZnHApUPy/DEX15%. In-vitro drug release studies confirmed sustained release of DEX over a period of 12 days for GelUPy/nZnHApUPy composites with no remarkable initial burst compared to that of the pure GelUPy. Overall, our data suggests that the DEX carrying supramolecular nanocomposite can be used as an osteogenic hydrogel scaffold for bone tissue engineering applications.

Engineering atorvastatin loaded Mg-Mn/LDH nanoparticles and their composite with PLGA for bone tissue applications.

The impact of mixing method in conventional co-precipitation synthesis of layered double hydroxides (LDHs), on particle size, size distribution and drug loading capacity is reported. Synthesis of Mg (II)/Mn (III)-LDH nano-platelets was performed at constant pH using three different mixing systems, magnetic stirrer, mechanical mixer, and homogenizer at ambient temperature and a fixed Mg/Mn ratio of 3/1. The LDH characterization results showed that mechanical mixing and homogenization lead to production of very fine LDH nano-platelets (about 90-140 nm), with narrow particle size distribution. Amount of the intercalated drug was determined as about 60% and showed a significant increase in loading capacity of the LDH through homogenization and mechanical mixing compared to that of the magnetic stirring (about 35%). Our results also showed that in LDH preparation via co-precipitation, the mixing system plays a more influential role in particle size, size distribution, and drug loading control, than the mixing speed of each system. Drug loaded-LDH/PLGA composites were prepared via electrospinning to afford a bioactive/osteoinductive scaffold. A remarkable degree of cell viability on the scaffolds (drug-loaded-LDH/PLGA composite) was confirmed using MTT assay. Osteogenic differentiation of human ADMSCs, as shown by alkaline phosphatase activity and Alizarin Red staining assays, indicated that the scaffold with 5% drug loaded LDH(Mn-Mg-LDH/PLGA/AT5%) induced a remarkably higher level of the markers compared to the PLGA scaffold and therefore, it could be a valuable candidate for bone tissue engineering applications.

Preparation of Nanoparticle-Containing Ring-Implanted Poly(Vinyl Alcohol) Contact Lens for Sustained Release of Hyaluronic Acid.

Here, a novel ring-implanted poly vinyl alcohol (PVA) contact lens (CL) is fabricated and evaluated as a therapeutic CL with potential of sustained release of hyaluronic acid (HA). HA is loaded on chitosan (CS) nanoparticles (NPs) and then the HA-loaded NPs are dispersed in a ring shape PVA hydrogel which is implanted in the final PVA CL. Results show that HA is successfully loaded on NPs (520 ± 18 nm) with loading efficacy of 87% and loading capacity of 50%. The CL hydrogel has a 275% swelling ratio, no degradation during 14 days, 97% light transmittance, and desirable rheological stability under physiological shear force. The release data show a sustained release for HA from the ring implanted CL up to 14 days. The cellular study reveals no corneal epithelial cell cytotoxicity and cell attachment on the CL. The study demonstrates the successful application of the ring-implanted CL to sustain the delivery of HA for treating the dry eye syndrome.

Controlled curcumin release from nanofibers based on amphiphilic-block segmented polyurethanes.

A series of biodegradable amphiphilic-block segmented polyurethanes (SPUs) are designed and synthesized based on di-block and tri-block macrodiols of polycaprolactone (PCL) and polyethylene glycol (PEG). Curcumin, as a model herbal antibacterial agent, is used due to its effective inhibitory action against Gram-positive and Gram-negative bacteria. Curcumin-loaded nanofibers, with 400-900 nm diameter range, have been prepared by electrospinning of SPUs. The synthesized SPUs can be used for wound dressing applications due to their excellent mechanical properties and higher hydrophilicity in comparison to PCL-based polyurethane. The elongation-at-break of tri-block SPU with PEG-PCL-PEG soft segments is 350% when produced as an electrospun mat and that for film is 1500%. In vitro release of curcumin, examined by UV-Vis spectroscopy, shows a steady release during 18 days. The inclusion of PEG chains in the soft segment increases the hydrophilicity and biodegradation rate of the electrospun mats compared to a PCL-based polyurethane, which eventually results in a higher curcumin release rate. The antibacterial activity of 50 mg of 10% curcumin-loaded SPU nanofibers is about 100% and 93% against Escherichia coli (E. coli ATCC: 25922) and Staphylococcus aureus (S. aureus ATCC: 6538), respectively. Nontoxic behavior of the scaffolds is evaluated through MTT assay against L929 mouse fibroblast cells. The results show that the synthesized SPUs can be used as a nanoscale sustained release carrier. The SPU with PEG-PCL-PEG soft segments is an excellent candidate for wound dressing in tissues undergoing large deformations during normal activities.

Vitamin C Loaded Poly(urethane-urea)/ZnAl-LDH Aligned Scaffolds Increase Proliferation of Corneal Keratocytes and Up-Regulate Vimentin Secretion.

A novel poly(urethane-urea) (PUU) based on poly(glycolide-co-ε-caprolactone) macro-diol with tunable mechanical properties and biodegradation behavior is reported for corneal stromal tissue regeneration. Zn-Al layered double hydroxide (LDH) nanoparticles were synthesized and loaded with vitamin C (VC, VC-LDH) and dispersed in the PUU to control VC release in the cell culturing medium. To mimic the corneal stromal EC, scaffolds of the PUU and its nanocomposites with VC-LDH (PUU-LDH and PUU-VC-LDH) were fabricated via electrospinning. Average diameters of the aligned nanofibers were recorded as 325 ± 168, 343 ± 171, and 414 ± 275 nm for the PUU, PUU-LDH, and PUU-VC-LDH scaffolds, respectively. Results of hydrophilicity and mechanical properties measurements showed increased hydrophobicity and reduced tensile strength and elongation at break upon addition of nanoparticles to the PUU scaffold. VC release studies represented that intercalation of the drug in Zn-Al-LDH controlled the burst release and extended the release period from a few hours to 5 days. Viability and proliferation of stromal keratocyte cells on the scaffolds were investigated via AlamarBlue assay. After 24 h, the cells showed similar viability on the scaffolds and the control. After 1 week, the cells showed some degree of proliferation on the scaffolds, with the highest value recorded for PUU-VC-LDH. SEM images of the scaffolds after 24 h and 1 week confirmed good penetration and attachment of keratocytes on all the scaffolds and the cells oriented with the direction of nanofibers. After 1 week, the PUU-VC-LDH scaffold was fully covered by the cells. Immunocytochemistry assay (ICC) was performed to investigate secretion of vimentin protein, ALDH3A1, and α-SMA by the cells. After 24h and 1 week, remarkably higher levels of vimentin and ALDH3A1 and lower level of α-SMA were secreted by keratocytes on PUU-VC-LDH compared to those on the PUU and PUU-LDH scaffolds and the control. Our results suggest that the aligned PUU-VC-LDH is a promising candidate for corneal stromal tissue engineering due to the presence of zinc and vitamin C.

Atorvastatin loaded PLGA microspheres: Preparation, HAp coating, drug release and effect on osteogenic differentiation of ADMSCs.

Polymer/bioceramic composite micro-particles have been used for bone regeneration in order to address weak mechanical properties/bioactivity of polymers and to enable easy filling of irregular bone defects through minimally invasive injection procedure. The purpose of this study was to determine whether injectable apatite-coated atorvastatin (AT) loaded Poly (d,l-lactide-co-glycolide) (PLGA) micro-particles can support osteogenic differentiation of adipose derived mesenchymal stem cells(ADMSCs). Particle preparation conditions (oil-in-water (O/W) emulsion), were carefully adjusted to yield uniform particles of about 20-50 µm in diameter. Taking a solid in oil-in water (S/O/W) emulsion strategy, it became possible to load atorvastatin (10 wt%) in the micro-particles without deformation. The particles were then coated with HAp by incubation in 10X simulated body fluid (SBF). The apatite coating layer was similar to apatite in natural bone, as demonstrated by SEM, XRD, and FTIR analyses. Adipose derived mesenchymal stem cells (ADMSCs), were cultured on the micro-particles and calcium deposition measurement was performed through Alizarin Red assay. Initial cell adhesion did not differ significantly between the samples and the control. The strongest osteogenic differentiation was observed on PLGA-AT-HAp in both the osteogenic and non osteogenic culture media, while PLGA-AT slightly decreased and PLGA-HAp slightly increased osteogenic differentiation of the cells, indicating suitability of PLGA-AT-HAp as an injectable tissue engineering system.

Structure-properties relationships in dental adhesives: Effect of initiator, matrix monomer structure, and nano-filler incorporation.

OBJECTIVES: This is a confirmatory study to evaluate the effect of photoinitiator type and concentration, matrix monomer chemical structure, and nanoparticle incorporation on the physical and mechanical properties of an experimental dentin bonding agent. MATERIALS AND METHODS: Different concentrations of camphorquinone-amine (CQ-A) system, butanedione (BD), and phenylpropanedione (PPD), as photoinitiator, BTDMA, as a comonomer containing carboxylic acid groups, and silica nanoparticles as reinforcing inorganic filler were incorporated into a methacrylate base experimental dental adhesive. The effect of these ingredients, as independent variables, on the shrinkage kinetics, flexural strength and modulus, and microshear bond strength of the adhesives were then investigated. The results were analyzed using one-way ANOVA and Tukey's post-hoc test at the significance level of 0.05. RESULTS: The results indicate that the efficiency of CQ-A initiator system is diminished in the presence of the acidic monomer BTDMA while the photopolymerization is efficiently progressed with BD as initiator. PPD shows the lowest efficiency in the photopolymerization of the adhesives. BTDMA as a monomer with the capability of interaction with tooth structure provides adhesive with improved microshear bond strength to dentin. Incorporation of silica nanoparticles at low concentrations enhances the flexural and microshear strength of the dentin bonding agent. SIGNIFICANCE: Understanding the structure-property relationship in dental adhesives may help the material selection in clinical dentistry. The study elucidates the relationship between monomer structure, initiator type, and nanofiller and physical and mechanical properties in dental adhesives.

Correction to: Compositional design and Taguchi optimization of hardness properties in silicone-based ocular lenses.

The original version of this article unfortunately contained a mistake: The spelling of the Ebrahim Gafar-Zadehs' name was incorrect. The corrected name is given above.

Compositional design and Taguchi optimization of hardness properties in silicone-based ocular lenses.

A multi-component acrylate-based copolymer system especially designed for application as ocular lenses is developed through free-radical, bulk polymerization of a system containing hydroxyethyl methacrylate, methyl methacrylate, triethylene glycol dimethacrylate, dimethyl itaconate, 3-(trimethoxysilyl) propylmethacrylate, Polyhedraloligomeric silsesquioxane-acrylate (POSS-acrylate) and AIBN as an initiator. The progress of the reaction was monitored by Fourier transform infrared spectroscopy (FTIR). The effect of increasing concentration of the components on the hardness of the synthesized lenses was measured by Shore Durometer before and after immersion in PBS solutions. Extraction test method was performed to analyze the biocompatibility of the fabricated lenses. In this research the Taguchi method was employed to achieve the optimal hardness property which plays a critical role in final application of the lens materials. The Taguchi trial for ocular lens hardness was configured in an L16 orthogonal array, by five control factors, each with four level settings. The results showed that 3-(trimethoxysilyl) propyl methacrylate decreases and 2-hydroxyethylmethacrylate increases, polyhedraloligomeric silsesquioxane with a cage-like structure, methyl methacrylate and dimethyl itaconate increase the hardness. Proliferation and growth of the cells showed that there is no toxic substance extracted from the lenses which can interfere with the cell growth.

Poly (Ethylene Glycol)-Based Hydrogels as Self-Inflating Tissue Expanders with Tunable Mechanical and Swelling Properties.

Tissue expansion is used by plastic/reconstructive surgeons to grow additional skin/tissue for replacing or repairing lost or damaged soft tissues. Recently, hydrogels have been widely used for tissue expansion applications. Herein, a self-inflating tissue expander blend composition from three different molecular weights (2, 6, and 10 kDa) of poly (ethylene glycol) diacrylate (PEGDA) hydrogel with tunable mechanical and swelling properties is presented. The in vitro results demonstrate that, of the eight studied compositions, P6 (PEGDA 6 kDa:10 kDa (50:50)) and P8 (PEGDA 6 kDa:10 kDa (35:65)) formulations provide a balance of mechanical property and swelling capability suitable for tissue expansion. Furthermore, these expanders can be compressed up to 60% of their original height and can be loaded and unloaded cyclically at least ten times with no permanent deformation. The in vivo results indicate that these two engineered blend compositions are capable to generate a swelling pressure sufficient to dilate the surrounding tissue while retaining their original shape. The histological analyses reveal the formation of fibrous capsule at the interface between the implant and the subcutaneous tissue with no signs of inflammation. Ultimately, controlling the PEGDA chain length shows potential for the development of self-inflating tissue expanders with tunable mechanical and swelling properties.

Effect of hydroxyapatite nano-particles on morphology, rheology and thermal behavior of poly(caprolactone)/chitosan blends.

The effect of hydroxyapatite nano-particles (nHA) on morphology, and rheological and thermal properties of PCL/chitosan blends was investigated. The tendency of nHA to reside in the submicron-dispersed chitosan phase is determined using SEM and AFM images. The presence of electrostatic interaction between amide sites of chitosan and ionic groups on the nHA surface was proved by FTIR. It is shown that the chitosan phase is thermodynamically more favorable for the nano-particles to reside than the PCL phase. Lack of implementation of Cox-Merz theory for this system shows that the polymer-nano-particle network is destructed by the flow. Results from dynamic rheological measurements and Zener fractional model show that the presence of nHA increases the shear moduli and relaxation time of the PCL/chitosan blends. DSC measurements showed that nHA nano-particles are responsible for the increase in melting and crystallization characteristics of the PCL/chitosan blends. Based on thermogravimetric analysis, the PCL/chitosan/nHA nano-composites exhibited a greater thermal stability compared to the nHA-free blends.

PCL/chitosan/Zn-doped nHA electrospun nanocomposite scaffold promotes adipose derived stem cells adhesion and proliferation.

Chitosan (Ch), and poly(ɛ-caprolactone) (PCL), widely used as biomaterials with desirable properties for tissue engineering applications, were both blended with zinc-doped hydroxyapatite nanoparticles(nZnHA) and electrospun into nanofibrous scaffolds using formic acid/acetic acid. The rationale behind this study was to demonstrate that presence of small quantities of Zn(2+) ions doped in HA nanoparticles can improve biocompatibility of PCL/Ch blends. SEM observation revealed that average fiber diameter was increased from about 136 nm for a PCL/Ch blend, to around 210 nm for PCL/Ch/nZnHA nanocomposite. PCL/Ch/nZnHA scaffolds offered higher elastic modulus (about 3-fold) and tensile strength (nearly 1.5-fold) than the corresponding PCL/Ch scaffolds. In-vitro biocompatibility studies using human adipose derived stem cells (hAD-MSCs), demonstrated that the presence of only 5 wt% nZnHA in PCL/Ch/nZnHA nanocomposites enhanced hAD-MSCs' attachment compared to PCL/Ch and PCL/Ch/nHA. Finally, hAD-MSCs proliferation occurred at significantly higher rates of 1.5, 1.3 and 1.2 times on PCL/Ch/nZnHA scaffold compared to PCL, PCL/Ch and PCL/Ch/nHA, respectively.

Effect of interface on mechanical properties and biodegradation of PCL HAp supramolecular nano-composites.

This research explores the correlation between the structural properties of supramolecular biocomposites and their mechanical strength. Hybrid biocomposites composed of surface-modified hydroxyapatite nano-particles and supramolecular polycaprolactone (SP PCL), were prepared at different compositions, and their mechanical, thermal and viscoelastic properties as well as biodegradability, biocompatibility and cytotoxicity were evaluated in vitro. The results were compared with those for SP PCL/naked hydroxyapatite nano-composites. We show that surface modification of hydroxyapatite nanoparticles resulted in outstanding improvement of tensile strength and modulus up to 3.6 and 2.2-fold, respectively. At above 10 wt% HAp and 20 wt% HApUPy, heterogeneous nano-composites with inferior mechanical properties were obtained. Based on rheological (in steady shear mode) and small/wide angle X-ray scattering measurements, unusual improved mechanical properties were ascribed to the formation of supramolecular clusters around nanoparticles. In-vitro degradation of the supramolecular nano-composites was also studied to investigate the overall product biodegradation as well as toxicity of the degradation product(s).

Biological and mechanical properties of novel composites based on supramolecular polycaprolactone and functionalized hydroxyapatite.

Supramolecular polymers based on quadruple hydrogen-bonding ureido-pyrimidinone (UPy) moieties hold promise as dynamic/stimuli-responsive materials in applications such as tissue engineering. Here, a new class of materials is introduced: supramolecular polymer composites. We show that despite the highly ordered structure and tacticity-dependent nature of hydrogen-bonded supramolecular polymers, the bioactivity of these polymers can be tuned through composite preparation with bioceramics. These novel supramolecular composites combine the superior processability of supramolecular polymers with the excellent bioactivity and mechanical characteristics of bioceramics. In particular, the bioactive composites prepared from supramolecular polycaprolactone and UPy-grafted hydroxyapatite (HApUPy) are described that can be easily formed into microporous biomaterials. The compression moduli increased about 40 and 90% upon composite preparation with HAp and HApUPy, respectively, as an indication to improved mechanical properties. These new materials show excellent potential as microporous composite scaffolds for the adhesion and proliferation of rat mesenchymal stem cells (rMSCs) as a first step toward bone regeneration studies; rMSCs proliferate about 2 and 2.7 times faster on the conventional composite with HAp and the supramolecular composite with (HApUPy) than on the neat PCL1250(UPy)(2).