Nanostructured Biopolymer-Based Constructs for Cartilage Regeneration: Fabrication Techniques and Perspectives.

The essential functions of cartilage, such as shock absorption and resilience, are hindered by its limited regenerative capacity. Although current therapies alleviate symptoms, novel strategies for cartilage regeneration are desperately needed. Recent developments in three-dimensional (3D) constructs aim to address this challenge by mimicking the intrinsic characteristics of native cartilage using biocompatible materials, with a significant emphasis on both functionality and stability. Through fabrication methods such as 3D printing and electrospinning, researchers are making progress in cartilage regeneration; nevertheless, it is still very difficult to translate these advances into clinical practice. The review emphasizes the importance of integrating various fabrication techniques to create stable 3D constructs. Meticulous design and material selection are required to achieve seamless cartilage integration and durability. The review outlines the need to address these challenges and focuses on the latest developments in the production of hybrid 3D constructs based on biodegradable and biocompatible polymers. Furthermore, the review acknowledges the limitations of current research and provides perspectives on potential avenues for effectively regenerating cartilage defects in the future.

Structurally stable and surface-textured polylactic acid/copolymer/poly (ε-caprolactone) blend-based electrospun constructs with tunable hydroxyapatite responsiveness.

Functionally-designed nanotextured and copolymer (COP) mediated PLA/PCL (70:30 w/w) blend-based interface-engineered electrospun mats (EMs) based constructs, with phase-specific interactions, have been successfully developed. The thermal stability of constructs remained up to ∼300-350 °C, while the crystallinity reduced to ∼12-23 %, indicating enhanced pliability. The tensile strength increased by ∼75 % without much compromise in the tensile modulus whereas the dynamic relaxation response of the constructs shifted to lower temperatures upon the incorporation of ≥ 2.5 phr (parts per hundred parts of resin) of COP. The zeta potential evaluated from radial surface exposure intensity could be manipulated by controlling the extent of COP content (-60 mV for ∼5 phr COP) which in turn led to the dynamics of site-specific charge neutralization driven attachment of Ca2+ ions (∼13 % for ∼5 phr COP) of the nano-hydroxyapatite (n-HA). Such uniformly dispersed, n-HA attached, and surface-decorated (COP ≤ 5 phr) EMs enabled the selective L929 fibroblast cell attachment (∼200 % cell viability for ∼2.5 phr COP). Thus, the approach may prove to augment the biomineralization of Ca and apatite-driven healing kinetics amongst implant-seeking and inflammation-prone sites and thereby, paving a new pathway for controlled and targeted healing of bone, cartilage, dental gums, and other sites demanding n-HA and/or calcium-phosphorus assisted healing mechanism.

Designing suture-proof cell-attachable copolymer-mediated and curcumin- ß-cyclodextrin inclusion complex loaded aliphatic polyester-based electrospun antibacterial constructs.

The paper demonstrates curcumin/ß-cyclodextrin-based inclusion complex (IC) loaded polyvinyl alcohol (PVA) dip-coated and copolymer-compatibilized polylactic acid (PLA)/poly(ε-caprolactone) (PCL) blend-based electrospun mats (EMs) as antibacterial, and suture-resistant constructs, to overcome the present challenges in developing structurally-stable, biocompatible, pliable, and stand-alone multifunctional-biomedical-devices. The thermal, microstructural, and viscoelastic characterization confirmed the presence of H-bonding interactions between IC and PVA moieties and between IC incorporated PVA matrix with the copolymer-mediated nanotextured PLA/PCL blend-based EMs. IC release and surface PVA erosion induced a decrease in modulus (>4-fold) and strength (>2-fold) of constructs (post-release). Mechanistically new and architectural-framework-defined PVA-gelation induced bi-axially diverted suture-failure (post-release) and resulted in a significant enhancement in suture-retention-strength (>3-fold), energy (>5-fold), and displacement (>2-fold) for ~20 wt% IC-loaded-PVA-coated EM-constructs. The fabricated EM-constructs exhibited improvement in surface-hydrophilicity (contact angle ~45°), surface nano-roughness (~ 600 nm), surface area (~34 m2/g), pore volume (~3.6 × 10-2 cc/g), IC release efficacy (~20 % burst release), antibacterial activity (adherent bacteria <10 %) against E. coli and S. aureus, and L929 fibroblast-cell-viability (~135 %), which varied as a function of IC-content in the PVA matrix. Our study conceptually establishes a novel and efficient technique for designing antibacterial, suture-resistant engineered-EM-constructs with tunable properties for their potential use in wound-dressings, periodontal-membranes, drug-delivery, and regenerative-systems.

Tuning structural-response of PLA/PCL based electrospun nanofibrous mats: Role of dielectric-constant and electrical-conductivity of the solvent system.

The role of optimum solvent systems on the fabrication of uniform, bead-free electrospun-nanofibrous-mats (ENMs) of polylactic acid (PLA), poly(ε-caprolactone) (PCL), and their blends, is investigated. The solvent systems influenced the fiber-diameters, morphology, crystallinity, thermal stability, hydrophobicity, quasi-static mechanical, and solid-state visco-elastic responses of the ENMs. Defect-free ENMs were obtained by using CF/DMF (80:20 v/v) binary solvent system while showing a relatively higher extent of crystallinity (PLA/PCL blend ∼ 34%), lower hydrophobicity (PLA ∼ 1170), higher strength (PLA ∼ 6 MPa), and moduli (PLA ∼ 305 MPa) for PLA and PLA/PCL blend systems whereas a higher strain-at-break (∼ 82%) was shown by PCL based ENMs. PLA/PCL blend based ENMs fabricated using DCM/DMF (80:20 v/v) solvent-mixture exhibited comparatively lower crystallinity (∼ 25%) but higher fiber diameter (1.03 ± 0.21 µm), strain-at-break (∼ 155%), and hydrophobicity (∼ 1300) compared to CF/DMF (80:20 v/v) system. Dynamic mechanical analysis (DMA) revealed the structural relaxation behaviors indicating the intrinsic structural deformability and flexibility of the mats. The study demonstrated the systematic role of solvent characteristics in terms of their volatility, dielectric constant, and solvent-mixture composition on the electro-spinnability and fabrication of high-strength, deformable, hydrophobic, bead-free ENMs with near monodisperse fibrous assemblies for biomedical applications.

Recent advances in polymer scaffolds for biomedical applications.

The review provides insights into current advancements in electrospinning-assisted manufacturing for optimally designing biomedical devices for their prospective applications in tissue engineering, wound healing, drug delivery, sensing, and enzyme immobilization, and others. Further, the evolution of electrospinning-based hybrid biomedical devices using a combined approach of 3 D printing and/or film casting/molding, to design dimensionally stable membranes/micro-nanofibrous assemblies/patches/porous surfaces, etc. is reported. The influence of various electrospinning parameters, polymeric material, testing environment, and other allied factors on the morphological and physico-mechanical properties of electrospun (nano-/micro-fibrous) mats (EMs) and fibrous assemblies have been compiled and critically discussed. The spectrum of operational research and statistical approaches that are now being adopted for efficient optimization of electrospinning process parameters so as to obtain the desired response (physical and structural attributes) has prospectively been looked into. Further, the present review summarizes some current limitations and future perspectives for modeling architecturally novel hybrid 3 D/selectively textured structural assemblies, such as biocompatible, non-toxic, and bioresorbable mats/scaffolds/membranes/patches with apt mechanical stability, as biological substrates for various regenerative and non-regenerative therapeutic devices.

From outbreak of COVID-19 to launching of vaccination drive: invigorating single-use plastics, mitigation strategies, and way forward.

The unforeseen outbreak of the COVID-19 epidemic has significantly stipulated the use of plastics to minimize the exposure and spread of the novel coronavirus. With the onset of the vaccination drive, the issue draws even more attention due to additional demand for vaccine packaging, transport, disposable syringes, and other allied devices scaling up to many million tonnes of plastic. Plastic materials in personal protective equipment (PPE), disposable pharmaceutical devices, and packaging for e-commerce facilities are perceived to be a lifesaver for the frontline healthcare personnel and the general public amidst recurring waves of the pandemic. However, the same material poses a threat as an evil environmental polluter when attributed to its indiscriminate and improper littering as well as mismanagement. The review not only highlights the environmental consequences due to the excessive use of disposable plastics amidst COVID-19 but also recommends mixed approaches to its management by adopting the combined and step-by-step methodology of adequate segregation, sterilization, sanitization activities, technological intervention, and process optimization measures. The overview finally concludes with some crucial way-forward measures and recommendations like the development of bioplastics and focusing on biodegradable/bio-compostable material alternatives to holistically deal with future pandemics.

Biodegradable and Biocompatible 3D Constructs for Dental Applications: Manufacturing Options and Perspectives.

Designing 3D constructs with appropriate materials and structural frameworks for complex dental restorative/regenerative procedures has always remained a multi-criteria optimization challenge. In this regard, 3D printing has long been known to be a potent tool for various tissue regenerative applications, however, the preparation of biocompatible, biodegradable, and stable inks is yet to be explored and revolutionized for overall performance improvisation. The review reports the currently employed manufacturing processes for the development of engineered self-supporting, easily processable, and cost-effective 3D constructs with target-specific tuneable mechanics, bioactivity, and degradability aspects in the oral cavity for their potential use in numerous dental applications ranging from soft pulp tissues to hard alveolar bone tissues. A hybrid synergistic approach, comprising of development of multi-layered, structurally stable, composite building blocks with desired physicomechanical performance and bioactivity presents an optimal solution to circumvent the major limitations and develop new-age advanced dental restorations and implants. Further, the review summarizes some manufacturing perspectives which may inspire the readers to design appropriate structures for clinical trials so as to pave the way for their routine applications in dentistry in the near future.

Understanding release kinetics and collapse proof suture retention response of curcumin loaded electrospun mats based on aliphatic polyesters and their blends.

The paper aims at designing and fabrication of PLA/PCL blended suture resistant electrospun mats (EMs) encapsulating non-toxic curcumin and optimization of its release behavior, to facilitate its sustained release at the targeted areas, without complexation with any chemical and/or synthetic drug. The release of curcumin from PLA/PCL blended EMs followed a diffusion-controlled mechanism, as evident from the agreement of the experimental release data with Peppas- Korsmeyer, Higuchi, and Kopcha model. The curcumin embedded EMs have effectively rendered a release confirming to a new generalized logarithmic model. PLA/PCL blended EMs have proved to be an excellent carrier system, exhibiting enhanced cumulative curcumin release with an increase in curcumin loading. The evaluation of structural and viscoelastic properties of the fabricated EMs showed an increase in modulus and strength, along with a subsequent decrease in elongation, with an increase in curcumin content. Suture-induced cooperative collapse dynamics the EMs have been found to be a three-stage process involving stable, stable-unstable, and fast-unstable structural failure corresponding to network realignment, lateral pullout/fracture of fibers, and divergent tearing along the crack path. The viscoelastic responses showed a prominent shift in glass transition temperature (Tg) of the PCL phase indicating the development of curcumin-induced microstructural changes attributed to the H-bonding interaction with polymer segments of PLA/PCL-based EMs. Our study demonstrates, functionally efficient designing of PLA/PCL-based curcumin-loaded biodegradable EMs with sustained retention of tunable mechanical properties and hydrophobicity, irrespective of the extent of (in-vitro) curcumin release.

Physicomechanical performance and encapsulation efficiency of ß-cyclodextrin loaded functional electrospun mats based on aliphatic polyesters and their blends.

Designing complex-forming biodegradable and biocompatible electrospun mats (EMs) by incorporating ß- cyclodextrin (ß-CD) into polylactic acid (PLA)/poly(ε-caprolactone) (PCL) (70:30 w/w) blend based polyester matrix. The influence of ß-CD loading on the morphological, thermal, and microstructural properties was investigated using scanning electron microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy. The studies revealed the presence of characteristic interactions between the polymer matrix and ß-CD moieties. Further, the quasi-static mechanical properties of EMs were evaluated using a universal testing machine. An enhancement in modulus and strength was obtained for ∼ 2.5-5 phr of ß-CD content and beyond ∼ 5 phr of ß-CD content, the mechanical properties of EMs were observed to deteriorate. The contact angle studies indicated a decrease in hydrophobicity of PLA/PCL-based EMs with the increase in ß-CD content. The swelling and weight loss studies in phosphate buffer saline (PBS) indicated a subsequent release of ß-CD from the EMs. FT-IR and 1H NMR spectra elucidated the removal of curcumin from ethanol-water solutions and its simultaneous encapsulation in ß-CD hydrophobic cavities (released) of fabricated EMs. Thus, the study demonstrates the development of aliphatic polyester-based biodegradable-functional EMs with tunable physico-mechanical properties for biomedical applications, facilitating encapsulation and rapid removal of waste hydrophobic ultrafine molecules from the system.

Optimally controlled morphology and physico-mechanical properties of inclusion complex loaded electrospun polyvinyl alcohol based nanofibrous mats for therapeutic applications.

Hydrophilic polyvinyl alcohol (PVA) based electrospun nanofibrous mats (ENMs) are recently being used for the designing and fabrication of active wound dressing materials. Thus, in this study an inclusion complex (IC) of curcumin (CUR) and ß-cyclodextrin (ß-CD) was optimally incorporated in electrospun PVA nanofibers, to obtain uniform bead-free nanofibers with minimum average diameter and variation using Taguchi's design of experiments (DOE). The optimum level parameters were ascertained using Taguchi's methodology, to obtain IC loaded PVA based bead-free ENMs, by varying IC (∼20, ∼40, and ∼60 wt.%) loading, applied voltage, solution concentration, and N, N-dimethylformamide (DMF) content in the electrospinning solution mixture. Validation experiments revealed a good agreement between the predicted and experimental values of fiber diameter, diameter-variation, and bead-numbers. Analysis of variance (ANOVA) showed a major influence of IC loading on the average fiber diameter and the number of bead defects, for IC-loaded PVA based ENMs. However, the DMF content of the solvent mixture significantly influenced the diameter variations of ENMs. The surface morphologies of ENMs were analyzed using Scanning Electron Microscopy (SEM) whereas the microstructural aspects were studied by Wide-Angle X-ray Diffraction (WAXD) and Fourier transform infrared (FT-IR) spectroscopy. The thermal properties were characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) whereas the mechanical properties were measured by using uniaxial tensile testing and dynamic mechanical analysis (DMA). The variation in properties of IC loaded PVA based ENMs were correlated with neat PVA based ENMs fabricated using a similar set of optimized electrospinning process parameters. The study conceptually demonstrated the optimal designing of structurally-engineered hydrophilic IC loaded PVA based ENMs by using the Taguchi approach based on orthogonal DOE as potential drug release substrates.

Structurally optimized suture resistant polylactic acid (PLA)/poly (є-caprolactone) (PCL) blend based engineered nanofibrous mats.

The structural fabrication and optimization of polylactic acid (PLA)/poly (є-caprolactone) (PCL) blend-based bead-free electrospun nanofibrous mats (ENMs) has been carried out by using Response Surface Methodology (RSM) and Taguchi design of experiments (DoE). From the three control parameters i.e., PCL content, N, N- dimethylformamide (DMF) content, and electrospinning solution concentration, the optimal parametric combinations for minimizing the bead defects amongst ENMs were obtained. The parametric optimization outcomes remained identical, from both RSM and Taguchi approaches, irrespective of the difference in the number of experimental trials. The experimental validation of the predicted results from Taguchi-design showed an excellent agreement with >95% accuracy concerning minimization of bead defects and average fiber diameter. The solution concentration was a key determinant in controlling the gross fiber morphology. The quasi-static mechanical response of the optimally designed ENMs showed a distinct role in structural aspects of fibers. The failure responses revealed the role of the structural network of ENMs in controlling the failure stress and network collapse that was also reiterated upon the outcomes of suture retention strength assessment. The optimally designed ENM structures showed a correspondingly optimal level of suture resistance, where fine fibers offered higher resistance to suture failure due to the cooperative network effects unlike the relatively coarse fiber-based ENMs undergoing collapse attributed to fiber buckling and fiber slippage in the labile structural network.

Nanofiller Dispersion, Morphology, Mechanical Behavior, and Electrical Properties of Nanostructured Styrene-Butadiene-Based Triblock Copolymer/CNT Composites.

A nanostructured linear triblock copolymer based on styrene and butadiene with lamellar morphology is filled with multiwalled carbon nanotubes (MWCNTs) of up to 1 wt% by melt compounding. This study deals with the dispersability of the MWCNTs within the nanostructured matrix and its consequent impact on block copolymer (BCP) morphology, deformation behavior, and the electrical conductivity of composites. By adjusting the processing parameters during melt mixing, the dispersion of the MWCNTs within the BCP matrix are optimized. In this study, the morphology and glass transition temperatures (Tg) of the hard and soft phase are not significantly influenced by the incorporation of MWCNTs. However, processing-induced orientation effects of the BCP structure are reduced by the addition of MWCNT accompanied by a decrease in lamella size. The stress-strain behavior of the triblock copolymer/MWCNT composites indicate higher Young's modulus and pronounced yield point while retaining high ductility (strain at break ~ 400%). At a MWCNT content of 1 wt%, the nanocomposites are electrically conductive, exhibiting a volume resistivity below 3 × 103 Ω·cm. Accordingly, the study offers approaches for the development of mechanically flexible functional materials while maintaining a remarkable structural property profile.

Cytotoxic evaluation of hydroxyapatite-filled and silica/hydroxyapatite-filled acrylate-based restorative composite resins: An in vitro study.

STATEMENT OF PROBLEM: Although the physical and mechanical properties of hydroxyapatite-filled dental restorative composite resins have been examined, the biocompatibility of these materials has not been studied in detail. PURPOSE: The purpose of this in vitro study was to analyze the toxicity of acrylate-based restorative composite resins filled with hydroxyapatite and a silica/hydroxyapatite combination. MATERIAL AND METHODS: Five different restorative materials based on bisphenol A-glycidyl methacrylate (bis-GMA) and tri-ethylene glycol dimethacrylate (TEGDMA) were developed: unfilled (H0), hydroxyapatite-filled (H30, H50), and silica/hydroxyapatite-filled (SH30, SH50) composite resins. These were tested for in vitro cytotoxicity by using human bone marrow mesenchymal stromal cells. Surface morphology, elemental composition, and functional groups were determined by scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDX), and Fourier-transformed infrared spectroscopy (FTIR). The spectra normalization, baseline corrections, and peak integration were carried out by OPUS v4.0 software. RESULTS: Both in vitro cytotoxicity results and SEM analysis indicated that the composite resins developed were nontoxic and supported cell adherence. Elemental analysis with EDX revealed the presence of carbon, oxygen, calcium, silicon, and gold, while the presence of methacrylate, hydroxyl, and methylene functional groups was confirmed through FTIR analysis. CONCLUSIONS: The characterization and compatibility studies showed that these hydroxyapatite-filled and silica/hydroxyapatite-filled bis-GMA/TEGDMA-based restorative composite resins are nontoxic to human bone marrow mesenchymal stromal cells and show a favorable biologic response, making them potential biomaterials.