UNASSIGNED: The deployment of bone grafts (BGs) is critical to the success of scaffold-guided bone regeneration (SGBR) of large bone defects. It is thus critical to provide harvesting devices that maximize osteogenic capacity of the autograft while also minimizing graft damage during collection. As an alternative to the Reamer-Irrigator-Aspirator 2 (RIA 2) system - the gold standard for large-volume graft harvesting used in orthopaedic clinics today - a novel intramedullary BG harvesting concept has been preclinically introduced and referred to as the ARA (aspirator + reaming-aspiration) concept. The ARA concept uses aspiration of the intramedullary content, followed by medullary reaming-aspiration of the endosteal bone. This concept allows greater customization of BG harvesting conditions vis-à-vis the RIA 2 system. Following its successful in vitro validation, we hypothesized that an ARA concept-collected BG would have comparable in vivo osteogenic capacity compared to the RIA 2 system-collected BG.
UNASSIGNED: We used 3D-printed, medical-grade polycaprolactone-hydroxyapatite (mPCL-HA, wt 96 %:4 %) scaffolds with a Voronoi design, loaded with or without different sheep-harvested BGs and tested them in an ectopic bone formation rat model for up to 8 weeks.
UNASSIGNED: Active bone regeneration was observed throughout the scaffold-BG constructs, particularly on the surface of the bone chips with endochondral bone formation, and highly vascularized tissue formed within the fully interconnected pore architecture. There were no differences between the BGs derived from the RIA 2 system and the ARA concept in new bone volume formation and in compression tests (Young\'s modulus, p = 0.74; yield strength, p = 0.50). These results highlight that the osteogenic capacities of the mPCL-HA Voronoi scaffold loaded with BGs from the ARA concept and the RIA 2 system are equivalent.
UNASSIGNED: In conclusion, the ARA concept offers a promising alternative to the RIA 2 system for harvesting BGs to be clinically integrated into SGBR strategies.
UNASSIGNED: Our results show that biodegradable composite scaffolds loaded with BGs from the novel intramedullary harvesting concept and the RIA 2 system have equivalent osteogenic capacity. Thus, the innovative, highly intuitive intramedullary harvesting concept offers a promising alternative to the RIA 2 system for harvesting bone grafts, which are an important component for the routine translation of SGBR concepts into clinical practice.

Electrospun nanofibers exhibit a significant potential in the synthesis of nanostructured materials, thereby offering a promising avenue for enhancing the efficacy of wound care. The present study aimed to investigate the wound-healing potential of two biomacromolecules, PCL-Gelatin nanofiber adhered with bone marrow-derived mesenchymal stem cells (BMSCs). Characterisation of the nanofiber revealed a mean fiber diameter ranging from 200 to 300 nm, with distinctive elemental peaks corresponding to polycaprolactone (PCL) and gelatin. Additionally, BMSCs derived from bone marrow were integrated into nanofibers, and their wound-regenerative potential was systematically evaluated through both in-vitro and in-vivo methodologies. In-vitro assessments substantiated that BMSC-incorporated nanofibers enhanced cell viability and crucial cellular processes such as adhesion, and proliferation. Subsequently, in-vivo studies were performed to demonstrate the wound-healing efficacy of nanofibers. It was observed that the rate of wound healing of BMSCs incorporated nanofibers surpassed both, nanofiber and BMSCs alone. Furthermore, histomorphological analysis revealed accelerated re-epithelization and improved wound contraction in BMSCs incorporated nanofiber group. The fabricated nanofiber incorporated with BMSCs exhibited superior wound regeneration in animal model and may be utilised as a wound healing patch.

Alzheimer\'s disease (ALZ) is a neurological disorder characterized by cognitive decline. Rivastigmine (RV), an acetylcholinesterase inhibitor, is commonly used to treat ALZ. Unfortunately, RV is availablein capsule form, which is associated with low drug bioavailability, and in patch form, which can lead to skin irritation upon repeated use. This study successfully fabricated a trilayer dissolving microneedle (TDMN) containing RV with adequate mechanical strength by using the molding method. In vitro release and ex vivo permeation showed that the release and permeation of RV were significantly sustained compared to control without PCL. The release and permeation percentages were 91.34 ± 11.39 % and 13.76 ± 1.49 μg/cm2, respectively. In addition, the concentration of RV in plasma and brain after 168 h was measured to be 0.44 ± 0.09 µg/mL and 1.23 ± 0.26 µg/g, respectively, which reached the minimum concentration to inhibit AcHE and BuChe. Pharmacokinetic testing revealed higher AUC values after administration of TDMN, indicating better bioavailability, and RV concentrations in the brain were found to be twice as high as those achieved with oral administration. This study suggests TDMN may enhance the bioavailability and brain delivery of RV.

With respect to other fields, bone tissue engineering has significantly expanded in recent years, leading not only to relevant advances in biomedical applications but also to innovative perspectives. Polycaprolactone (PCL), produced in the beginning of the 1930s, is a biocompatible and biodegradable polymer. Due to its mechanical and physicochemical features, as well as being easily shapeable, PCL-based constructs can be produced with different shapes and degradation kinetics. Moreover, due to various development processes, PCL can be made as 3D scaffolds or fibres for bone tissue regeneration applications. This outstanding biopolymer is versatile because it can be modified by adding agents with antimicrobial properties, not only antibiotics/antifungals, but also metal ions or natural compounds. In addition, to ameliorate its osteoproliferative features, it can be blended with calcium phosphates. This review is an overview of the current state of our recent investigation into PCL modifications designed to impair microbial adhesive capability and, in parallel, to allow eukaryotic cell viability and integration, in comparison with previous reviews and excellent research papers. Our recent results demonstrated that the developed 3D constructs had a high interconnected porosity, and the addition of biphasic calcium phosphate improved human cell attachment and proliferation. The incorporation of alternative antimicrobials-for instance, silver and essential oils-at tuneable concentrations counteracted microbial growth and biofilm formation, without affecting eukaryotic cells\' viability. Notably, this challenging research area needs the multidisciplinary work of material scientists, biologists, and orthopaedic surgeons to determine the most suitable modifications on biomaterials to design favourable 3D scaffolds based on PCL for the targeted healing of damaged bone tissue.

Scaffold-guided breast tissue regeneration (SGBTR) can transform both reconstructive and cosmetic breast surgery. Implant-based surgery is the most common method. However, there are inherent limitations, as it involves replacement of tissue rather than regeneration. Regenerating autologous soft tissue has the potential to provide a more like-for-like reconstruction with minimal morbidity. Our SGBTR approach regenerates soft tissue by implanting additively manufactured bioresorbable scaffolds filled with autologous fat graft. A pre-clinical large animal study was conducted by implanting 100 mL breast scaffolds (n = 55) made from medical-grade polycaprolactone into 11 minipigs for 12 months. Various treatment groups were investigated where immediate or delayed autologous fat graft, as well as platelet rich plasma, were added to the scaffolds. Computed tomography and magnetic resonance imaging were performed on explanted scaffolds to determine the volume and distribution of the regenerated tissue. Histological analysis was performed to confirm the tissue type. At 12 months, we were able to regenerate and sustain a mean soft tissue volume of 60.9 ± 4.5 mL (95% CI) across all treatment groups. There was no evidence of capsule formation. There were no immediate or long-term post-operative complications. In conclusion, we were able to regenerate clinically relevant soft tissue volumes utilizing SGBTR in a pre-clinical large animal model.

This study was designed to deposit nanodiamonds on 3D-printed PCL scaffolds and evaluate their effect on the surface topography, hydrophilicity, degradation, and in-vitro cell adhesion compared to untreated PCL scaffolds. The PCL scaffold specimens were 3D-printed by fused deposition molding (FDM) technique with specific porosity parameters. The 3D-printed specimens\' surfaces were modified by nanodiamonds deposition followed by oxygen plasma post-treatment using a plasma focus (PF) device and a non-thermal atmospheric plasma jet (NTAPJ), respectively. Specimens were evaluated through morphological characterization by field emission scanning electron microscope (FESEM), microstructure characterization by Raman spectroscopy, chemical characterization by Fourier transform infrared (FTIR) spectroscopy, hydrophilicity degree by contact angle and water uptake measurements, and in-vitro degradation measurements (n=6). In addition, in-vitro bone marrow mesenchymal stem cells (BMSCs) adhesion was evaluated quantitatively by Confocal microscopy and qualitatively by FESEM at different time intervals after cell seeding (n=6). The statistical significance level was set at p ≤0.05. The FESEM micrographs, the Raman, and FTIR spectra confirmed the successful surface deposition of nanodiamonds on scaffold specimens. The nanodiamonds treated specimens showed nano-scale features distributed homogeneously across the surface compared to the untreated ones. Also, the nanodiamonds treated specimens revealed a statistically significant smaller contact angle (17.45 ±1.34 degrees), higher water uptake percentage after 24 h immersion in phosphate buffer saline (PBS) (21.56% ±1.73), and higher degradation rate after six months of immersion in PBS (43.92% ±0.77). Moreover, enhanced cell adhesion at all different time intervals was observed in nanodiamonds treated specimens with higher nuclei area fraction percentage (69.87% ±3.97) compared to the untreated specimens (11.46% ±1.34). Surface deposition of nanodiamonds with oxygen-containing functional groups on 3D-printed PCL scaffolds increased their hydrophilicity and degradation rate with significant enhancement of the in-vitro cell adhesion compared to untreated PCL scaffolds.

UNASSIGNED: 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.
UNASSIGNED: Topical administration of MET-PCL NPs-CS gel improves penetration of drug, decreases side effects, and increases efficacy of treatment.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for treating melanoma cancer after surgery was made using polycaprolactone and polymetformin microfibers that were loaded with doxycycline (PolyMet/PCL@DOX), an anti-cancer stem cell agent. The morphology, structure, mechanical characteristics, swelling, and porosity of the electrospun microfibers were examined. Drug release andanticancereffectiveness of PolyMet/PCL@DOXwas evaluated against A375 melanoma cancer stem cells using the MTS, Flow cytometry, colony formation and CD44 expression assays. Scanning electron microscopy (SEM) verified the micro fibrous structure with a diameter of about 2.31 µm. The porosity and swelling percentages for microfibers was 73.5 % and 2.9 %, respectively. The tensile strength at the breaking point was equal to 3.84 MPa. The IC50 of PolyMet/PCL@DOX was 7.4 μg/mL. The survival rate of A375 cells after 72 h of PolyMet/PCL@DOX treatment was 43.9 %. The colony formation capacity of A375 cells decreased after PolyMet/PCL@DOX treatment. The level of CD44 expression in the PolyMet/PCL@DOX group decreased compared to the control group. Generally, PolyMet/PCL@DOX microfibers can be a promising candidate as a patch after surgery to eradicate cancer stem cells, effectively.

In this study, a pH-responsive polycaprolactone (PCL)-copper peroxide (CuO2) composite antibacterial coating was developed by suspension flame spraying. The successful synthesis of CuO2 nanoparticles and fabrication of the PCL-CuO2 composite coatings were confirmed by microstructural and chemical analysis. The composite coatings were structurally homogeneous, with the chemical properties of PCL well maintained. The acidic environment was found to effectively accelerate the dissociation of CuO2, allowing the simultaneous release of Cu2+ and H2O2. Antimicrobial tests clearly revealed the enhanced antibacterial properties of the PCL-CuO2 composite coating against both Escherichia coli and Staphylococcus aureus under acidic conditions, with a bactericidal effect of over 99.99%. This study presents a promising approach for constructing pH-responsive antimicrobial coatings for biomedical applications.

Near-field direct-writing electrospinning technology can be used to produce ordered micro/nanofiber membrane dressings. The application of this technology can simply realize the control of dressing porosity, compound different functional substances, and adjust their distribution, thus improving the defects of common dressings such as insufficient breathability, poor moisture retention performance, and single function. Herein, a novel multifunctional wound dressing was prepared to utilize near-field direct-writing electrospinning technology, in which calf skin collagen type I (CSC-I) and polycaprolactone (PCL) were used as the composite matrix, Hexafluoroisopropanol (HFIP) as the solvent, and erythromycin (ERY) as an anti-infective drug component. The results show that the micro/nanofiber membranes prepared by near-field direct-writing electrospinning technology can all present a complete mesh structure, excellent thermal stability, and good moisturizing properties. Moreover, the composite fiber membrane loaded with ERY not only had obvious antibacterial properties against E. coli and S. thermophilus but also a better slow-release function of drugs (it is rare to have both in traditional wound dressings). Therefore, this experimental design can provide relevant theories and an experimental foundation for preparing a new type of medical dressing with drug loading and has good guiding significance for the application and promotion of near-field direct-writing electrospinning in medical dressings.