Biomedical Polymer Materials II

Polymeric joints, made of biomedical polyethylene (UHMWPE) nanocomposite sheets, were welded with a diode laser. Since polyethylene does not absorb laser light, nanocomposites were prepared containing different percentages by weight of titanium dioxide as it is a laser absorbent. The joints were first analyzed with static mechanical tests to establish the best percentage weight content of filler that had the best mechanical response. Then, the nanocomposites containing 1 wt% titanium dioxide were selected (white color) to be subjected to fatigue tests. The experimental results were also compared with those obtained on UMMWPE with a different laser light absorbent nano filler (carbon, with greater laser absorbing power, gray in color), already studied by our research team. The results showed that the two types of joints had an appreciable resistance to fatigue, depending on the various loads imposed. Therefore, they can be chosen in different applications of UHMWPE, depending on the stresses imposed during their use. Full article

Opportunely arranged micro/nano-scaled fibers represent an extremely attractive architecture for tissue engineering, as they offer an intrinsically porous structure, a high available surface, and an ideal microtopography for guiding cell migration. When fibers are made with naturally occurring polymers, matrices that closely mimic the architecture of the native extra-cellular matrix and offer specific chemical cues can be obtained. Along this track, electrospinning of collagen or gelatin is a typical and effective combination to easily prepare fibrous scaffolds with excellent properties in terms of biocompatibility and biomimicry, but an appropriate cross-linking strategy is required. Many common protocols involve the use of swelling solvents and can result in significant impairment of fibrous morphology and porosity. As a consequence, the efforts for processing gelatin into a fiber network can be vain, as a film-like morphology will be eventually presented to cells. However, this appears to be a frequently overlooked aspect. Here, the effect on fiber morphology of common cross-linking protocols was analyzed, and different strategies to improve the final morphology were evaluated (including alternative solvents, cross-linker concentration, mechanical constraint, and evaporation conditions). Finally, an optimized, fiber-preserving protocol based on carbodiimide (EDC) chemistry was defined. Full article

Superabsorbent hydrogels (SAHs) are three dimensional networks formed by polymers that can absorb aqueous solution of over 100% of their initial weight. This work aimed to develop and characterize SAHs of Chitosan/Xanthan gum (CG), Chitosan/Alginate (CA) and controlled Chitosan (C), Xanthan gum (G), and Alginate (A) produced using “onion-like” methodology. The swelling performance, the morphological structure, the crystallinity, and the Fourier transformed infrared spectroscopy characteristics of SAH were used for the characterization of polyelectrolytes complex. Swelling analysis showed that chitosan has a strong influence on the maintenance of hydrogels structure after swelling, mainly in the acid environment (pH = 2). The chitosan hydrogel presented around 3000% of acidic fluid absorption after 24 h. The chitosan:xanthan gum (1:1 and 2:1 named as C1G1 and C2G1, respectively) hydrogels were the best combination regarding swelling performance in an acid environment, reaching 1665% and 2024%, respectively, as well at pH 7.0, presenting 1005% (C1G1) and 667% (C2G1). Scanning electron microscopy analysis showed samples with pores, and with different shapes. The X-ray diffraction showed the presence of a characteristic peak at 2θ = 20° in all developed composition because of the crystalline nature of chitosan. This work shows the possibility of developing eco-friendly biopolymer-based SAHs at a low cost with a good swelling capacity and stability. Full article

Delivery systems to lymph node-resident T cells around tumor tissues are essential for cancer immunotherapy, in order to boost the immune responses. We previously reported that anionic dendrimers, such as carboxyl-, sulfonyl-, and phosphate-terminal dendrimers, were efficiently accumulated in lymph nodes via the intradermal injection. Depending on the terminal structure, their cell association properties were different, and the carboxyl-terminal dendrimers did not associate with any immune cells majorly. In this study, we investigated the delivery of carboxyl-terminal dendrimers with different hydrophobicity to lymph node-resident lymphocytes. Four types of carboxyl-terminal dendrimers—succinylated (C) and 2-carboxy-cyclohexanoylated (Chex) dendrimers with and without phenylalanine (Phe)—were synthesized and named C-den, C-Phe-den, Chex-den, and Chex-Phe-den, respectively. Chex-Phe-den was well associated with lymphocytes, but others were not. Chex-Phe-den, intradermally injected at the footpads of mice, was accumulated in the lymph node, and was highly associated with the lymphocytes, including T cells. Our results suggest that Chex-Phe-den has the potential for delivery to the lymph node-resident T cells, without any specific T cell-targeted ligands. Full article

Silicone rubber (SR) is a material used for medical procedures, with a common example of its application being in implants for cosmetic or plastic surgeries. It is also an essential component for the development of medical devices. SR was functionalized with the polymeric prodrug of poly(2-methacryloyloxy-benzoic acid) (poly(2MBA)) to render the analgesic anti-inflammatory drug salicylic acid by hydrolysis. The system was designed by functionalizing SR films (0.5 cm × 1 cm) with a direct grafting method, using gamma irradiation (⁶⁰Co source) to induce the polymerization process. The absorbed dose (from 20 to 100 kGy) and the monomer concentration (between 0.4 and 1.5 M) were critical in controlling the surface and the bulk modifications of SR. Grafting poly(2MBA) onto SR (SR-g-2MBA) were characterized by attenuated total reflectance Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy/energy-dispersive X-ray spectrometry, fluorescence microscopy, the contact angle, and the swelling. SR-g-2MBA demonstrated the drug’s sustained and pH-dependent release in simulated physiological mediums (pH = 5.5 and 7.4). The drug’s release was quantified by high-performance liquid chromatography and confirmed by gas chromatography–mass spectrometry. Finally, cytocompatibility was demonstrated in murine fibroblast and human cervical cancer cell lines. The developed systems provide new polymeric drug release systems for medical silicone applications. Full article

A modifier consisting of the mixture of cyclotriphosphazenes containing 4-allyl-2-methoxyphenoxy and β-carboxyethenylphenoxy moieties was developed for administration with acrylate dental restorative compositions. The synthesized compounds were characterized by ¹H and ¹³C NMR spectroscopy and MALDI-TOF mass spectrometry. The optimal conditions to combine the modifier with the starting dental mixture consisting of bis-GMA and TGM-3 were revealed by differential scanning calorimetry (DSC) method. Properties of the cured modified compositions were evaluated for the compliance with requirements of ISO 4049:2019. It was found that these compositions possess the increased adhesion to dental tissues and cure depth and the decreased water sorption and water solubility. The values of elastic modules, destructive compressive stress and microhardness were also increasing along with the increased content of the modifier in the composition. Full article

Recently, much effort has been expended on the development of non-viral gene delivery systems based on polyplexes of nucleic acids with various cationic polymers. Natural polysaccharide derivatives are promising carriers due to their low toxicity. In this work, chitosan was chemically modified by a reaction with 4-formyl-n,n,n-trimethylanilinium iodide and pyridoxal hydrochloride and subsequent reduction of the imine bond with NaBH₄. This reaction yielded three novel derivatives, n-[4-(n’,n’,n’-trimethylammonium)benzyl]chitosan chloride (TMAB-CS), n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (Pyr-CS), and n-[4-(n’,n’,n’’-trimethylammonium)benzyl]-n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (PyrTMAB-CS). Their structures and degrees of substitution were established by ¹H NMR spectroscopy as DS₁ = 0.22 for TMAB-CS, DS₂ = 0.28 for Pyr-CS, and DS₁ = 0.21, DS₂ = 0.22 for PyrTMAB-CS. Dynamic light scattering measurements revealed that the new polymers formed stable polyplexes with plasmid DNA encoding the green fluorescent protein (pEGFP-N3) and that the particles had the smallest size (110–165 nm) when the polymer:DNA mass ratio was higher than 5:1. Transfection experiments carried out in the HEK293 cell line using the polymer:DNA polyplexes demonstrated that Pyr-CS was a rather poor transfection agent at polymer:DNA mass ratios less than 10:1, but it was still more effective than the TMAB-CS and PyrTMAB-CS derivatives that contained a quaternary ammonium group. By contrast, TMAB-CS and PyrTMAB-CS were substantially more effective than Pyr-CS at higher polymer:DNA mass ratios and showed a maximum efficiency at 200:1 (50%–70% transfected cells). Overall, the results show the possibility of combining substituent effects in a single carrier, thereby increasing its efficacy. Full article

In this paper, a new formulation of biodegradable and bioresorbable chitosan-based hydrogel for controlled drug release was investigated. A chitosan–dendrimer–hydroxyapatite hydrogel, obtained by covalently grafting chitosan powder with an hyperbranched PAMAM dendrimer followed by in-situ precipitation of hydroxyapatite and gelification, was synthesized and characterized by FTIR, NMR, TGA, XRD and rheological studies. The hydrogels have been also doped with an anti-inflammatory drug (ketoprofen) in order to investigate their drug release properties. Chemical and chemical-physical characterizations confirmed the successful covalent functionalization of chitosan with PAMAM and the synthesis of nanostructured hydroxyapatite. The developed hydrogel made it possible to obtain an innovative system with tunable rheological and drug-releasing properties relative to the well-known formulation containing chitosan and hydroxyapatite powder. The developed hydrogel showed different rheological and drug-releasing properties of chitosan matrix mixed with hydroxyapatite as a function of dendrimer molecular weight; therefore, the chitosan–dendrimer–hydroxyapatite hydrogel can couple the well-known osteoconductive properties of hydroxyapatite with the drug-release behavior and good processability of chitosan–dendrimer hydrogels, opening new approaches in the field of tissue engineering based on biopolymeric scaffolds. Full article

Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor δ (PPARδ) in cartilage may attenuate the development or progression of OA. PPARδ antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt.% drug and had mean diameters of about 600 nm. Differential scanning calorimetry indicated the drug was in crystalline domains in the particles. Atomic force microscopy was used to measure the Young’s moduli of individual particles as 2.8 MPa. In vitro drug release studies showed 11% GSK3787 was released over 30 days. Studies in immature murine articular cartilage (IMAC) cells indicated low toxicity from the drug, empty particles, and drug-loaded particles and that the particles were not taken up by the cells. Ex vivo studies on murine joints showed that the particles could be injected into the joint space and resided there for at least 7 days. Overall, these results indicate that GSK3787-loaded PEA particles warrant further investigation as a delivery system for potential OA therapy. Full article

Glucose-sensitive films were prepared through the layer-by-layer (LbL) deposition of hemin-modified poly(ethyleneimine) (H-PEI) solution and DNA solution (containing glucose oxidase (GOx)). H-PEI/DNA + GOx multilayer films were constructed using electrostatic interactions. The (H-PEI/DNA + GOx)₅ film was then partially decomposed by hydrogen peroxide (H₂O₂). The mechanism for the decomposition of the LbL film was considered to involve more reactive oxygen species (ROS) that were formed by the reaction of hemin and H₂O₂, which then caused nonspecific DNA cleavage. In addition, GOx present in the LbL films reacts with glucose to generate hydrogen peroxide. Therefore, decomposition of the (H-PEI/DNA + GOx)₅ film was observed when the thin film was immersed in a glucose solution. (H-PEI/DNA + GOx)₅ films exposed to a glucose solution for periods of 24, 48 72, and 96 h indicated that the decomposition of the film increased with the time to 9.97%, 16.3%, 23.1%, and 30.5%, respectively. The rate of LbL film decomposition increased with the glucose concentration. At pH and ionic strengths close to physiological conditions, it was possible to slowly decompose the LbL film at low glucose concentrations of 1–10 mM. Full article

Despite the high regenerative capacity of bone tissue, there are some cases where bone repair is insufficient for a complete functional and structural recovery after damage. Current surgical techniques utilize natural and synthetic bone grafts for bone healing, as well as collagen sponges loaded with drugs. However, there are certain disadvantages associated with these techniques in clinical usage. To improve the therapeutic efficacy of bone tissue regeneration, a number of drug delivery systems based on biodegradable natural and synthetic polymers were developed and examined in in vitro and in vivo studies. Recent studies have demonstrated that biodegradable polymers play a key role in the development of innovative drug delivery systems and tissue engineered constructs, which improve the treatment and regeneration of damaged bone tissue. In this review, we discuss the most recent advances in the field of polymer-based drug delivery systems for the promotion of bone tissue regeneration and the physical-chemical modifications of polymers for controlled and sustained release of one or more drugs. In addition, special attention is given to recent developments on polymer nano- and microparticle-based drug delivery systems for bone regeneration. Full article

In this article, recent advances in the development, preparation, biocompatibility and mechanical properties of polyetheretherketone (PEEK) and its composites for hard and soft tissue engineering are reviewed. PEEK has been widely employed for fabricating spinal fusions due to its radiolucency, chemical stability and superior sterilization resistance at high temperatures. PEEK can also be tailored into patient-specific implants for treating orbital and craniofacial defects in combination with additive manufacturing process. However, PEEK is bioinert, lacking osseointegration after implantation. Accordingly, several approaches including surface roughening, thin film coating technology, and addition of bioactive hydroxyapatite (HA) micro-/nanofillers have been adopted to improve osseointegration performance. The elastic modulus of PEEK is 3.7–4.0 GPa, being considerably lower than that of human cortical bone ranging from 7–30 GPa. Thus, PEEK is not stiff enough to sustain applied stress in load-bearing orthopedic implants. Therefore, HA micro-/nanofillers, continuous and discontinuous carbon fibers are incorporated into PEEK for enhancing its stiffness for load-bearing applications. Among these, carbon fibers are more effective than HA micro-/nanofillers in providing additional stiffness and load-bearing capabilities. In particular, the tensile properties of PEEK composite with 30wt% short carbon fibers resemble those of cortical bone. Hydrophobic PEEK shows no degradation behavior, thus hampering its use for making porous bone scaffolds. PEEK can be blended with hydrophilic polymers such as polyglycolic acid and polyvinyl alcohol to produce biodegradable scaffolds for bone tissue engineering applications. Full article

There is a rising demand for replacement, regeneration of tissues and organ repairs for patients who suffer from diseased/damaged bones or tissues such as hip pains. The hip replacement treatment relies on the implant, which may not always meet the requirements due to mechanical and biocompatibility issues which in turn may aggravate the pain. To surpass these limitations, researchers are investigating the use of scaffolds as another approach for implants. Three-dimensional (3D) printing offers significant potential as an efficient fabrication technique on personalized organs as it is capable of biomimicking the intricate designs found in nature. In this review, the determining factors for hip replacement and the different fabrication techniques such as direct 3D printing, Fused Deposition Modelling (FDM), Selective Laser Sintering (SLS) and stereolithography (SLA) for hip replacement. The study also covers surface modifications of 3D printed implants and provides an overview on 3D tissue regeneration. To appreciate the current conventional hip replacement practices, the conventional metallic and ceramic materials are covered, highlighting their rationale as the material of choice. Next, the challenges, ethics and trends in the implants’ 3D printing are covered and conclusions drawn. The outlook and challenges are also presented here. The knowledge from this review indicates that 3D printing has enormous potential for providing a pathway for a sustainable hip replacement. Full article

In order to overcome the shortcomings related to unspecific and partially efficient conventional wound dressings, impressive efforts are oriented in the development and evaluation of new and effective platforms for wound healing applications. In situ formed wound dressings provide several advantages, including proper adaptability for wound bed microstructure and architecture, facile application, patient compliance and enhanced therapeutic effects. Natural or synthetic, composite or hybrid biomaterials represent suitable candidates for accelerated wound healing, by providing proper air and water vapor permeability, structure for macro- and microcirculation, support for cellular migration and proliferation, protection against microbial invasion and external contamination. Besides being the most promising choice for wound care applications, polymeric biomaterials (either from natural or synthetic sources) may exhibit intrinsic wound healing properties. Several nanotechnology-derived biomaterials proved great potential for wound healing applications, including micro- and nanoparticulate systems, fibrous scaffolds, and hydrogels. The present paper comprises the most recent data on modern and performant strategies for effective wound healing. Full article

Due to their mechanical properties, ranging from flexible to hard materials, polyurethanes (PUs) have been widely used in many industrial and biomedical applications. PUs’ characteristics, along with their biocompatibility, make them successful biomaterials for short and medium-duration applications. The morphology of PUs includes two structural phases: hard and soft segments. Their high mechanical resistance featuresare determined by the hard segment, while the elastomeric behaviour is established by the soft segment. The most important biomedical applications of PUs include antibacterial surfaces and catheters, blood oxygenators, dialysis devices, stents, cardiac valves, vascular prostheses, bioadhesives/surgical dressings/pressure-sensitive adhesives, drug delivery systems, tissue engineering scaffolds and electrospinning, nerve generation, pacemaker lead insulation and coatings for breast implants. The diversity of polyurethane properties, due to the ease of bulk and surface modification, plays a vital role in their applications. Full article

Light-initiated polymerization processes are currently an important tool in various industrial fields. The advancement of technology has resulted in the use of photopolymerization in various biomedical applications, such as the production of 3D hydrogel structures, the encapsulation of cells, and in drug delivery systems. The use of photopolymerization processes requires an appropriate initiating system that, in biomedical applications, must meet additional criteria such as high water solubility, non-toxicity to cells, and compatibility with visible low-power light sources. This article is a literature review on those compounds that act as photoinitiators of photopolymerization processes in biomedical applications. The division of initiators according to the method of photoinitiation was described and the related mechanisms were discussed. Examples from each group of photoinitiators are presented, and their benefits, limitations, and applications are outlined. Full article