A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

Guiding the Path to Healing: CuO2 -Laden Nanocomposite Membrane for Diabetic Wound Treatment.

Diabetic chronic wounds pose significant clinical challenges due to their characteristic features of impaired extracellular matrix (ECM) function, diminished angiogenesis, chronic inflammation, and increased susceptibility to infection. To tackle these challenges and provide a comprehensive therapeutic approach for diabetic wounds, the first coaxial electrospun nanocomposite membrane is developed that incorporates multifunctional copper peroxide nanoparticles (n-CuO2 ). The membrane's nanofiber possesses a unique "core/sheath" structure consisting of n-CuO2 +PVP (Polyvinylpyrrolidone)/PCL (Polycaprolactone) composite sheath and a PCL core. When exposed to the wound's moist environment, PVP within the sheath gradually disintegrates, releasing the embedded n-CuO2 . Under a weakly acidic microenvironment (typically diabetic and infected wounds), n-CuO2 decomposes to release H2 O2 and Cu2+ ions and subsequently produce ·OH through chemodynamic reactions. This enables the anti-bacterial activity mediated by reactive oxygen species (ROS), suppressing the inflammation while enhancing angiogenesis. At the same time, the dissolution of PVP unveils unique nano-grooved surface patterns on the nanofibers, providing desirable cell-guiding function required for accelerated skin regeneration. Through meticulous material selection and design, this study pioneers the development of functional nanocomposites for multi-modal wound therapy, which holds great promise in guiding the path to healing for diabetic wounds.

Synthesis of Nanosized γ-Cyclodextrin Metal-Organic Frameworks as Carriers of Limonene for Fresh-Cut Fruit Preservation Based on Polycaprolactone Nanofibers.

To address the issue of bacterial growth on fresh-cut fruits, this paper reports the synthesis of nanosized γ-cyclodextrin metal-organic frameworks (CD-MOFs) using an ultrasound-assisted method and their application as carriers of limonene for antibacterial active packaging. The effects of the processing parameters on the morphology and crystallinity of the CD-MOFs are investigated, and the results prove that the addition of methanol is the key to producing nanosized CD-MOFs. The limonene loading content of the nanosized CD-MOFs can reach approximately 170 mg g-1. The sustained-release behaviors of limonene in the CD-MOFs are evaluated. Molecular docking simulations reveal the distribution and binding sites of limonene in the CD-MOFs. CD-MOFs are deposited on the surfaces of polycaprolactone (PCL) nanofibers via an immersion method, and limonene-loaded CD-MOF@PCL nanofibers are prepared. The morphology, crystallinity, thermal stability, mechanical properties, and antibacterial activity of the nanofibers are also studied. The nanofiber film effectively inhibits bacterial growth and prolongs the shelf life of fresh-cut apples. This study provides a novel strategy for developing antibacterial active packaging materials based on CD-MOFs and PCL nanofibers.

Selective Delivery of Clindamycin Using a Combination of Bacterially Sensitive Microparticle and Separable Effervescent Microarray Patch on Bacteria Causing Diabetic Foot Infection.

INTRODUCTION: Diabetic foot infection (DFI) is one of the complications of diabetes mellitus. Clindamycin (CLY) is one of the antibiotics recommended to treat DFI, but CLY given orally and intravenously still causes many side effects. METHODS: In this study, we encapsulated CLY in a bacteria sensitive microparticle system (MP-CLY) using polycaprolactone (PCL) polymer. MP-CLY was then delivered in a separable effervescent microarray patch (MP-CLY-SEMAP), which has the ability to separate between the needle layer and separable layer due to the formation of air bubbles when interacting with interstitial fluid in the skin. RESULT: The characterization results of MP-CLY proved that CLY was encapsulated in large amounts as the amount of PCL polymer used increased, and there was no change in the chemical structure of CLY. In vitro release test results showed increased CLY release in media cultured with Staphylococcus aureus bacteria and showed controlled release. The characterization results of MPCLY-SEMAP showed that the developed formula has optimal mechanical and penetration capabilities and can separate in 56 ± 5.099 s. An ex vivo dermatokinetic test on a bacterially infected skin model showed an improvement of CLY dermatokinetic profile from MP-CLY SEMAP and a decrease in bacterial viability by 99.99%. CONCLUSION: This research offers proof of concept demonstrating the improved dermatokinetic profile of CLY encapsulated in a bacteria sensitive MP form and delivered via MP-CLY-SEMAP. The results of this research can be developed for future research by testing MP-CLY-SEMAP in vivo in appropriate animal models.

Combining Step-Growth and Chain-Growth Polymerizations in One Pot: Light-Induced Fabrication of Conductive Nanoporous PEDOT-PCL Scaffold.

A novel method based on light-induced fabrication of a poly (3,4-ethylenedioxythiophene)-polycaprolactone (PEDOT-PCL) scaffold using phenacyl bromide (PAB) as a single-component photoinitiator is presented. HBr released from the step-growth polymerization of EDOT is utilized as an in situ catalyst for the chain-growth polymerization of ε-caprolactone. Detailed investigations disclose the formation of a self-assembled nanoporous electroconductive scaffold (1.2 mS cm-1 ). Fluorescence emission spectra of the fabricated scaffold exhibit a mixed solvatochromic behavior, indicating specific interactions between the self-assembled scaffold and solvents with varying polarities, as evidenced by transmission electron microscopy (TEM). Moreover, the same light-induced technique can also be applied for bulk photopolymerization showcasing the versatility and wide-ranging scope of the originated method. In brief, this study introduces a novel approach for light-induced polymerization reactions that is merging step-growth and chain-growth mechanisms. This innovative approach is promising to facilitate in situ polymerization of monomers possessing diverse functionalities.

Calcium phosphate coating enhances osteointegration of melt electrowritten scaffold by regulating macrophage polarization.

The osteoimmune microenvironment induced by implants plays a significant role in bone regeneration. It is essential to efficiently and timely switch the macrophage phenotype from M1 to M2 for optimal bone healing. This study examined the impact of a calcium phosphate (CaP) coating on the physiochemical properties of highly ordered polycaprolactone (PCL) scaffolds fabricated using melt electrowritten (MEW). Additionally, it investigated the influence of these scaffolds on macrophage polarization and their immunomodulation on osteogenesis. The results revealed that the CaP coated PCL scaffold exhibited a rougher surface topography and higher hydrophilicity in comparison to the PCL scaffold without coating. Besides, the surface morphology of the coating and the release of Ca2+ from the CaP coating were crucial in regulating the transition of macrophages from M1 to M2 phenotypes. They might activate the PI3K/AKT and cAMP-PKA pathways, respectively, to facilitate M2 polarization. In addition, the osteoimmune microenvironment induced by CaP coated PCL could not only enhance the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro but also promote the bone regeneration in vivo. Taken together, the CaP coating can be employed to control the phenotypic switching of macrophages, thereby creating a beneficial immunomodulatory microenvironment that promotes bone regeneration.

Unveiling the Inner Structure of Micrometric Hollow Polymeric Fibers Using Synchrotron X-Ray Nanotomography.

In this study, a novel application of synchrotron X-ray nanotomography based on high-resolution full-field transmission X-ray microscopy for characterizing the structure and morphology of micrometric hollow polymeric fibers is presented. By employing postimage analysis using an open-source software such as Tomviz and ImageJ, various key parameters in fiber morphology, including diameter, wall thickness, wall thickness distribution, pore size, porosity, and surface roughness, were assessed. Electrospun polycaprolactone fibers with micrometric diameters and submicrometric features with induced porosity via gas dissolution foaming were used to this aim. The acquired synchrotron X-ray nanotomography data were analyzed using two approaches: 3D tomographic reconstruction and 2D radiographic projection-based analysis. The results of the combination of both approaches demonstrate unique capabilities of this technique, not achievable by other available techniques, allowing for a full characterization of the internal and external morphology and structure of the fibers as well as to obtain valuable qualitative insights into the overall fiber structure.

3D-printed polycaprolactone scaffolds coated with beta tricalcium phosphate for bone regeneration.

BACKGROUND/PURPOSE: 3D-printing technology is an important tool for the bone tissue engineering (BTE). The aim of this study was to investigate the interaction of polycaprolactone (PCL) scaffolds and modified mesh PCL coated with beta TCP (PCL/ß-TCP) scaffolds with MG-63. METHODS: This study used the fused deposition modeling (FDM) technique with the 3D printing technique to fabricate the thermoplastic polymer and composite scaffolds. Scaffold structure and coating quality were observed under a scanning electron microscope (SEM). MG-63 cells were injected and attached to the mesh-manufactured PCL scaffolds. The biocompatibility of mesh structured PCL and PCL/ß-TCP scaffolds could be examined by measuring the viability of MG-63 cells of MTT assay. Bone cell differentiation was evaluated ALP activity by mineralization assay. RESULTS: The results showed that both mesh PCL scaffolds and PCL/ß-TCP scaffolds were non-toxic to the cells. The ALP activities of cells in PCL/ß-TCP scaffolds groups were significant differences and better than PCL groups in all groups at all experimental dates. The mineralization process was time-dependent, and significantly higher mineralization of osteosarcoma cells was observed on PCL/ß-TCP scaffolds at experimental dates. CONCLUSION: We concluded that both meshes structured PCL and PCL/ß-TCP scaffolds could promote the MG-63 cell growth, and PCL/ß-TCP was better than the PCL scaffolds for the outcome of MG63 cell differentiation and mineralization.

In vitro and ex vivo evaluation of chitosan gel containing metformin-loaded polymeric nanoparticles for topical treatment of melanoma.

OBJECTIVE: The purpose of this study was to prepare and evaluate chitosan (CS) gel containing metformin hydrochloride (MET)-loaded polycaprolactone (PCL) nanoparticles (NPs) for topical treatment of melanoma. SIGNIFICANCE: Topical administration of MET-PCL NPs-CS gel improves penetration of drug, decreases side effects, and increases efficacy of treatment. METHODS: MET-PCL NPs were prepared by double emulsion method. Particle size, charge, encapsulation efficiency (EE), release, and morphology were evaluated. MET-PCL NPs-CS gel formulation was characterized in terms of organoleptic properties, pH, gelling time, viscosity, spreadability, release, and morphology. Cytotoxicity was performed on B16F10 cells. Ex vivo permeability was done with pig skin. RESULTS: The size, charge, and EE were found to be 180 ± 10 nm, -11.4 mV, and 93%. SEM images showed that NPs were spherical and smooth. An initial burst release followed by a slower release was observed. MET-PCL NPs-CS gel was found to be transparent. The pH was 4.9 ± 0.05. The gelation time was 1.6 ± 0.2 min. The viscosity results confirm pseudoplastic behavior of gel. The spreadability by % area was 392 ± 6.4 cm. The images showed that gelling network of CS gel was composed of suspended NPs. The viscosity was between 554 and 3503 cP. MET-PCL NPs-CS gel showed prolonged release up to 72 h. On B16F10 cells, gel showed higher cytotoxicity compared to MET solution. MET-PCL NPs-CS gel had twofold higher permeability in pig skin compared with MET-CS gel. CONCLUSION: Topical administration of MET-PCL NPs-CS gel into the skin resulted in improved dermal penetration and this promising approach may be of value in effective treatment of melanoma and other skin cancers.

Function Follows Form: Oriented Substrate Nanotopography Overrides Neurite-Repulsive Schwann Cell-Astrocyte Barrier Formation in an In Vitro Model of Glial Scarring.

Schwann cell (SC) transplantation represents a promising therapeutic approach for traumatic spinal cord injury but is frustrated by barrier formation, preventing cell migration, and axonal regeneration at the interface between grafted SCs and reactive resident astrocytes (ACs). Although regenerating axons successfully extend into SC grafts, only a few cross the SC-AC interface to re-enter lesioned neuropil. To date, research has focused on identifying and modifying the molecular mechanisms underlying such scarring cell-cell interactions, while the influence of substrate topography remains largely unexplored. Using a recently modified cell confrontation assay to model SC-AC barrier formation in vitro, highly oriented poly(ε-caprolactone) nanofibers were observed to reduce AC reactivity, induce extensive oriented intermingling between SCs and ACs, and ultimately enable substantial neurite outgrowth from the SC compartment into the AC territory. It is anticipated that these findings will have important implications for the future design of biomaterial-based scaffolds for nervous tissue repair.

Design and construction of chemical-biological module clusters for degradation and assimilation of poly(ethylene terephthalate) waste.

The rising accumulation of poly(ethylene terephthalate) (PET) waste presents an urgent ecological challenge, necessitating an efficient and economical treatment technology. Here, we developed chemical-biological module clusters that perform chemical pretreatment, enzymatic degradation, and microbial assimilation for the large-scale treatment of PET waste. This module cluster included (i) a chemical pretreatment that involves incorporating polycaprolactone (PCL) at a weight ratio of 2% (PET:PCL = 98:2) into PET via mechanical blending, which effectively reduces the crystallinity and enhances degradation; (ii) enzymatic degradation using Thermobifida fusca cutinase variant (4Mz), that achieves complete degradation of pretreated PET at 300 g/L PET, with an enzymatic loading of 1 mg protein per gram of PET; and (iii) microbial assimilation, where Rhodococcus jostii RHA1 metabolizes the degradation products, assimilating each monomer at a rate above 90%. A comparative life cycle assessment demonstrated that the carbon emissions from our module clusters (0.25 kg CO2-eq/kg PET) are lower than those from other established approaches. This study pioneers a closed-loop system that seamlessly incorporates pretreatment, degradation, and assimilation processes, thus mitigating the environmental impacts of PET waste and propelling the development of a circular PET economy.

Hybrid Green Materials Obtained by PCL Melt Blending with Diatomaceous Earth.

In this work, diatomaceous earth (Diat) was explored as filler for polycaprolactone (PCL) to obtain composite green materials with promising viscoelastic and thermal properties. The composites were prepared by blending variable Diat amounts (5, 15 and 50 wt%) with a molten PCL matrix. The viscoelastic characteristics of PCL/Diat hybrids were studied by Dynamic Mechanical Analysis (DMA) under an oscillatory regime, while the thermal properties were determined by Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). We detected that the presence of Diat enhances the energy storage capacity of PCL for temperatures lower than the polymer melting point. Both DMA and DSC data revealed that the PCL melting temperature is slightly affected by the Diat addition, while the TGA results showed that the thermal stability of the polymer can be significantly improved by mixing PCL with diatomaceous earth. Moreover, we observed that the dispersion of Diat into the matrix favors the crystallization process of PCL. Interestingly, the improvements of PCL properties (elasticity, thermal stability, and crystallinity) are proportional to the Diat concentration of the composites. These findings reflect the interfacial compatibility between PCL and diatomaceous earth. In conclusion, this study highlights that the preparation of PCL/Diat hybrids by melt blending is suitable for the development of composite materials for technological applications, including the remediation of air pollutants within museum environments.

Biodegradable Polymers in Veterinary Medicine-A Review.

During the past two decades, tremendous progress has been made in the development of biodegradable polymeric materials for various industrial applications, including human and veterinary medicine. They are promising alternatives to commonly used non-degradable polymers to combat the global plastic waste crisis. Among biodegradable polymers used, or potentially applicable to, veterinary medicine are natural polysaccharides, such as chitin, chitosan, and cellulose as well as various polyesters, including poly(ε-caprolactone), polylactic acid, poly(lactic-co-glycolic acid), and polyhydroxyalkanoates produced by bacteria. They can be used as implants, drug carriers, or biomaterials in tissue engineering and wound management. Their use in veterinary practice depends on their biocompatibility, inertness to living tissue, mechanical resistance, and sorption characteristics. They must be designed specifically to fit their purpose, whether it be: (1) facilitating new tissue growth and allowing for controlled interactions with living cells or cell-growth factors, (2) having mechanical properties that address functionality when applied as implants, or (3) having controlled degradability to deliver drugs to their targeted location when applied as drug-delivery vehicles. This paper aims to present recent developments in the research on biodegradable polymers in veterinary medicine and highlight the challenges and future perspectives in this area.

Synthesis and Morphology Characteristics of New Highly Branched Polycaprolactone PCL.

A simple and efficient method for the synthesis of biodegradable, highly branched polycaprolactone (PCL) is presented. The solvent-free (bulk) reaction was carried out via ring opening polymerization (ROP), catalyzed by tin octanoate Sn(Oct)2, and it employed hyperbranched polyamide (HPPA) as a macro-initiator. The core-shell structure of the obtained products (PCL-HPPA), with the hyperbranched HPPA core and linear PCL chains as shell, was in the focus of the product characterization. 1H nuclear magnetic resonance (1H NMR) and elemental analysis confirmed the covalent incorporation of the HPPA in the products, as well as a high degree of grafting conversion of its amino functional groups. Confocal Raman Micro spectroscopy, and especially Time-of-Flight Secondary Ion Mass Spectrometry, further supported the existence of a core-shell structure in the products. Direct observation of macromolecules by means of cryogenic transmission electron microscopy, as well as gel permeation chromatography (GPC), suggested the existence of a minor 'aggregated' product fraction with multiple HPPA cores, which was attributed to transesterification reactions. Differential scanning calorimetry, as well as X-ray diffraction, demonstrated that the PCL-HPPA polymers displayed a similar degree of crystallinity to linear neat PCL, but that the branched products possessed smaller and less regular crystallites.

Eradication of Pseudomonas aeruginosa biofilm using quercetin-mediated copper oxide nanoparticles incorporated in the electrospun polycaprolactone nanofibrous scaffold.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that form biofilms in chronic wounds and is difficult to treat with standard treatment methods. In the present study, flavonoid quercetin-mediated CuONPs (Que-CuONPs) were successfully synthesized and incorporated in the electrospun polycaprolactone (Que-CuONPs-PCL) nanofibrous membrane to eradicate the burn wound infection causing P. aeruginosa biofilm. The fabricated scaffold Que-CuONPs-PCL was characterized using HR-SEM, EDX, XRD, and FTIR. The synthesized Que-CuONPs appeared as spherical in shape with the average size of 36 nm. The crystallite size of the synthesized CuONPs was calculated as 23 nm. Antibacterial activity results shows that the ZOI and MIC of Que-CuONPs against P. aeruginosa was found to be 20 mm and 5 µg/mL, respectively. Antibiofilm assay results indicate the pre-formed P. aeruginosa biofilm was completely eradicated by Que-CuONPs at 8-MIC. The Que-CuONPs-PCL nanofibrous scaffolds exhibits less cytotoxic effects on mouse fibroblast (L929) cells. Finally, this study highlights the fabricated Que-CuONPs-PCL nanofibrous scaffolds exhibits an excellent antibiofilm effect against P. aeruginosa biofilm with a great biocompatibility.

Fabrication of an electrospun polycaprolactone substrate for colorimetric bioassays.

Colorimetric assays rely on detecting colour changes to measure the concentration of target molecules. Paper substrates are commonly used for the detection of biomarkers due to their availability, porous structure, and capillarity. However, the morphological and mechanical properties of paper, such as fibre diameter, pore size, and tensile strength, cannot be easily tuned to meet the specific requirements of colorimetric sensors, including liquid capacity and reagent immobilisation. As an alternative to paper materials, biodegradable polymeric membranes made of electrospun polycaprolactone (PCL) fibres can provide various tunable properties related to fibre diameter and pore size.We aimed to obtain a glucose sensor substrate for colorimetric sensing using electrospinning with PCL. A feeding solution was created by mixing PCL/chloroform and 3,3',5',5'-tetramethylbenzidine (TMB)/ethanol solutions. This solution was electrospun to fabricate a porous membrane composed of microfibres consist of PCL and TMB. The central area of the membrane was made hydrophilic through air plasma treatment, and it was subsequently functionalized with a solution containing glucose oxidase, horseradish peroxidase, and trehalose.The sensing areas were evaluated by measuring colour changes in glucose solutions of varying concentrations. The oxidation reactions of glucose and TMB in sensor substrates were recorded and analysed to establish the correlation between different glucose concentrations and colour changes. For comparison, conventional paper substrates prepared with same parameters were evaluated alongside the electrospun PCL substrates. As a result, better immobilization of reagents and higher sensitivity of glucose were achieved with PCL substrates, indicating their potential usage as a new sensing substrate for bioassays.

Fibrin gel enhanced trilayer structure in cell-cultured constructs.

Efficient cell seeding and subsequent support from a substrate ensure optimal cell growth and neotissue development during tissue engineering, including heart valve tissue engineering. Fibrin gel as a cell carrier may provide high cell seeding efficiency and adhesion property, improved cellular interaction, and structural support to enhance cellular growth in trilayer polycaprolactone (PCL) substrates that mimic the structure of native heart valve leaflets. This cell carrier gel coupled with a trilayer PCL substrate may enable the production of native-like cell-cultured leaflet constructs suitable for heart valve tissue engineering. In this study, we seeded valvular interstitial cells onto trilayer PCL substrates with fibrin gel as a cell carrier and cultured them for 1 month in vitro to determine if this gel can improve cell proliferation and production of extracellular matrix within the trilayer cell-cultured constructs. We observed that the fibrin gel enhanced cellular proliferation, their vimentin expression, and collagen and glycosaminoglycan production, leading to improved structure and mechanical properties of the developing PCL cell-cultured constructs. Fibrin gel as a cell carrier significantly improved the orientations of the cells and their produced tissue materials within trilayer PCL substrates that mimic the structure of native heart valve leaflets and, thus, may be highly beneficial for developing functional tissue-engineered leaflet constructs.

Concomitant Effect of Quercetin and Its Copper Complex in the Development of Sustained-Release Nanoparticles of Polycaprolactone, Used for the Treatment of Skin Infection.

The study aimed to improve the treatment of impetigo with naturally occurring quercetin and its copper-quercetin (Cu-Q) complex by preparing sustained-release (SR) nanoparticles of polycaprolactone (PCL). The solvent evaporation method was used for the copper-quercetin (Cu-Q) complex formation, and their PCL nanoparticles (PCL-NPs, Q-PCL-NPs, and Cu-Q-PCL-NPs) were prepared by the high-pressure homogenization method. Synthesis of nanoparticles was confirmed by their physicochemical and antibacterial properties of quercetin against Gram-positive as well as Gram-negative bacteria. The percentage loading efficiency of quercetin and release in 100 mM of phosphate buffer pH 7.4 and 5.5 at 37 °C was found to be more than 90% after 24 h with the zero-order release pattern. Minimum inhibitory concentration of nanoparticles was found to increase threefold in the case of Cu-Q-PCL-NPs may be due to the synergistic antibacterial behavior. Scanning electron microscopy showed spherical nanoparticles, and surface roughness was confirmed by atomic force microscopy analysis. Fortunately, no sign of irritation on rat skin even at 3%, was seen. In vitro antioxidant assay by 2,2-diphenyl-1-picrylhydrazyl reduction was found to be ≤80 ± 0.02% which confirmed their scavenging activity. Interestingly, for the ex vivo study, the tape-stripping model was applied against Staphylococcus aureus containing rats and showed the formation of the epidermal layer within 4-5 days. Confirmation of antibacterial activity of pure quercetin, from Cu-Q complex, and their SR release from Q-PCL-NPs and Cu-Q-PCL-NPs was considered an effective tool for the treatment of skin diseases and can be used as an alternative of already resistant ciprofloxacin in impetigo.

A Tunable Calcium Phosphate Coating to Drive in vivo Osseointegration of Composite Engineered Tissues.

Varying degrees of hydroxyapatite (HA) surface functionalization have been implicated as the primary driver of differential osteogenesis observed in infiltrating cells. The ability to reliably create spatially controlled areas of mineralization in composite engineered tissues is of growing interest in the field, and the use of HA-functionalized biomaterials may provide a robust solution to this challenge. In this study, we successfully fabricated polycaprolactone salt-leached scaffolds with two levels of a biomimetic calcium phosphate coating to examine their effects on MSC osteogenesis. Longer duration coating in simulated body fluid (SBF) led to increased HA crystal nucleation within scaffold interiors as well as more robust HA crystal formation on scaffold surfaces. Ultimately, the increased surface stiffness of scaffolds coated in SBF for 7 days in comparison to scaffolds coated in SBF for 1 day led to more robust osteogenesis of MSCs in vitro without the assistance of osteogenic signaling molecules. This study also demonstrated that the use of SBF-based HA coatings can promote higher levels of osteogenesis in vivo. Finally, when incorporated as the endplate region of a larger tissue-engineered intervertebral disc replacement, HA coating did not induce mineralization in or promote cell migration out of neighboring biomaterials. Overall, these results verified tunable biomimetic HA coatings as a promising biomaterial modification to promote discrete regions of mineralization within composite engineered tissues.

Development of a double-layer electrospun patch as a potential prenatal treatment for myelomeningocele.

Myelomeningocele (MMC) is a congenital defect of the spine characterised by meningeal and spinal cord protrusion through the open vertebral arches. This defect causes progressive prenatal damage of the spinal cord, leading to lifelong handicap. Although mid-trimester surgical repair may reduce part of the handicap, an earlier and less invasive approach would further improve the prognosis, possibly minimising maternal and foetal risks. Several studies have proposed an alternative approach to surgical repair by covering the defect with a patch and protecting the exposed neural tissue. Our study aims to elaborate on a waterproof and biodegradable bioactive patch for MMC prenatal foetal repair. We developed a double-layer patch that can provide a waterproof coverage for the spinal cord, with a bioactive side, conducive to cell proliferation, and an antiadhesive side to avoid its attachment to the medulla.