Search Results (72)

Star polymers—macromolecules featuring multiple arms radiating from a central core—offer unique potential for biomedical applications due to their tunable architecture, multifunctionality and ability to incorporate stimuli-responsive and biocompatible components. In this study, functional star polymers with oligo (ethylene glycol) methyl ether methacrylate (OEOMA) arms and 2-(dimethylamino)ethyl methacrylate (DMAEMA) core units were synthesized via atom transfer radical polymerization (ATRP) using the “arm-first” strategy. The star polymers were used as nanoreactors for the in situ reduction of silver nitrate to form silver nanoparticles (AgNPs) without additional reducing agents. UV–Vis spectroscopy confirmed the formation of spherical AgNPs with absorption maxima around 430 nm, and transmission electron microscopy revealed uniform particle morphology. These hybrid nanomaterials (STR-AgNPs) were incorporated into polymethyl methacrylate (PMMA)-based bone cement to impart antibacterial properties. Mechanical testing showed that the compressive strength remained within acceptable limits, while antibacterial assays against E. coli demonstrated a significant inhibition of bacterial growth. These findings suggest that STR-AgNPs serve as promising candidates for infection-resistant bone implants, providing localized antibacterial effects while maintaining mechanical integrity and biocompatibility. Full article

Long-acting injectable (LAI) formulations have revolutionized veterinary pharmaceuticals by improving patient compliance, minimizing dosage frequency, and improving therapeutic efficacy. These formulations utilize advanced drug delivery technologies, including microspheres, liposomes, oil solutions/suspensions, in situ-forming gels, and implants to achieve extended drug release. Biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL) have been approved by the USFDA and are widely employed in the development of various LAIs, offering controlled drug release and minimizing the side effects. Various classes of veterinary medicines, including non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, and reproductive hormones, have been successfully formulated as LAIs. Some remarkable LAI products, such as ProHeart^® (moxidectin), Excede^® (ceftiofur), and POSILACTM (recombinant bovine somatotropin), show clinical relevance and commercial success. This review provides comprehensive information on the formulation strategies currently being used and the emerging technologies in LAIs for veterinary purposes. Additionally, challenges in characterization, in vitro testing, in vitro in vivo correlation (IVIVC), and safety concerns regarding biocompatibility are discussed, along with the prospects for next-generation LAIs. Continued advancement in the field of LAI in veterinary medicine is essential for improving animal health. Full article

Complex anatomical and physiological barriers make the eye a challenging organ to treat from a drug delivery perspective. Currently available treatment methods (topical eyedrops) for anterior segment diseases pose several limitations in terms of bioavailability and patient compliance. Conventional drug delivery methods to treat posterior segment ocular diseases are primarily intravitreal injection (IVT) of solutions. IVT is highly invasive and leads to retinal toxicity, endophthalmitis, and intraocular inflammation, frequently requiring professional administration and frequent clinical visits. Advanced drug delivery treatment strategies could improve patient compliance and convenience. Long-acting drug delivery platforms (biodegradable or nonbiodegradable) provide sustained/controlled release of drugs for at least four to six months. Smart drug delivery alternatives, for instance, in situ forming implants, are injectable formulations that form semisolid-to-solid implants in response to the various stimuli of pH, light, osmolarity, and temperature. Additionally, nanoparticulate drug delivery systems, contact lenses, electrospun patches, and microneedle-based drug delivery systems provide minimally invasive treatment options for ocular disorders. This comprehensive review focuses on advanced drug delivery options for the management of ocular disorders. Full article

Poly(lactide-co-glycolide) (PLGA) implants have become a cornerstone in drug delivery and regenerative medicine due to their biocompatibility, tunable degradation, and capacity for sustained, localized therapeutic release. Recent innovations in polymer design, fabrication methods, and functional modifications have expanded their utility across diverse clinical domains, including oncology, neurology, orthopedics, and ophthalmology. This review provides a comprehensive analysis of PLGA implant properties, fabrication strategies, and biomedical applications, while addressing key challenges such as burst release, incomplete drug release, manufacturing complexity, and inflammatory responses. Emerging solutions—such as 3D printing, in situ forming systems, predictive modeling, and patient-specific customization—are improving implant performance and clinical translation. Emphasis is placed on scalable production, long-term biocompatibility, and personalized design to support the next generation of precision therapeutics. Full article

Metallic biomaterials in a solid form cause stress-shielding in orthopedic applications. Such implants also suffer from limited tissue attachment to become a part of the living system. In view of that, hydroxyapatite (HA) coating reinforced with titanium oxide (TiO₂) was deposited in a beta (β)-Titanium (Ti-35Nb-7Ta-5Zr) substrate by plasma spray. This allows us to exploit the best of the two materials, namely the relatively low modulus of β-Ti, together with the porous and bone-like structure/composition of the HA to facilitate cell growth. This is foreseen to be used as an implant, particularly for musculoskeletal-related disability. Detailed scanning electron microscopy (SEM) investigation shows the lamellar structure of the coating that is composed of different phases and some porosities. Transmission electron microscopy (TEM) confirms the co-existence of both the amorphous and crystalline phases that build up the coating structure. In situ micro-mechanical tests revealed that the HA-TiO₂ coating was low in strength and modules compared to that of the substrate material, together with lower ductility. The yield stress and modulus of elasticity of the coating were about 877 ± 174 MPa and 447 ± 24 MPa, respectively. In contrast, the beta (β)-Ti substrate possesses about 990 ± 85 MPa of yield stress and 259 ± 19 MPa modulus of elasticity. The deformation mechanism was also quite different, where the coating crumbled under compressive loading, featuring limited ductility with cleavage (brittle)-type fracture, and the substrate showed plastic flow of materials in the form of slip/shear planes with extended ductility. Full article

Background: The combination of macroporous cryogels with synthetic peptide factors represents a promising but poorly explored strategy for the development of extracellular matrix (ECM)-mimicking scaffolds for peripheral nerve (PN) repair. Methods: In this study, IKVAV peptide was functionalized with terminal lysine residues to allow its in situ cross-linking with gelatin macromer, resulting in the formation of IKVAV-containing proteinaceous cryogels. The controllable inclusion and distribution of the peptide molecules within the scaffold was verified using a fluorescently labelled peptide counterpart. The optimized cryogel scaffold was combined with polycaprolactone (PCL)-based shell tube to form a suturable nerve conduit (NC) to be implanted into sciatic nerve diastasis in rats. Results: The NC constituents did not impair the viability of primary skin fibroblasts. Concentration-dependent effects of the peptide component on interrelated viscoelastic and swelling properties of the cryogels as well as on proliferation and morphological differentiation of neurogenic PC-12 cells were established, also indicating the existence of an optimal-density range of the introduced peptide. The in vivo implanted NC sustained the connection of the nerve stumps with partial degradation of the PCL tube over eight weeks, whereas the core-filling cryogel profoundly improved local electromyographic recovery and morphological repair of the nerve tissues, confirming the regenerative activity of the developed scaffold. Conclusions: These results provide proof-of-concept for the development of a newly designed PN conduit prototype based on IKVAV-activated cryogel, and they can be exploited to create other ECM-mimicking scaffolds. Full article

The Plasma Immersion Ion Implantation (PIII) nitriding was used to form a modified layer rich in expanded austenite (γ_N) and expanded ferrite (α_N) phases in super duplex steel. The thermal stability of these phases was investigated through the in situ synchrotron X-ray diffraction. All the surfaces were analyzed by SEM, EDS, and nanoindentation. During the heating stage of the thermal treatments, the crystalline structure of the γ_N phase expanded thermally up to a temperature of 350 °C and, above this temperature, a reduction in the lattice parameter was observed due to the diffusion of nitrogen into the substrate. During the isothermal heating, the gradual diffusion of nitrogen continued and the lattice parameter of the γ_N phase decreased. Increasing the treatment temperature from 450 °C to 550 °C, a greater reduction in the lattice parameter of the γ_N phase occured and the peaks related to the CrN, α, and α_N phases became more evident in the diffractograms. This phenomenon is associated with the decomposition of the γ_N phase into CrN + α + α_N. After the heat treatments, the thickness of the modified layers increased and the hardness values close to the surface decreased, according to the diffusion of the nitrogen to the substrate. Full article

Objectives: Lower urinary tract symptoms (LUTSs) related to benign prostatic hyperplasia (BPH) are common in older men, and alpha-adrenoceptor blockers continue to be a key part of managing these symptoms. This study aimed to formulate injectable poly (lactic-co-glycolic acid) (PLGA) in situ-forming implants (ISFIs) loaded with silodosin (SLD) to address symptoms associated with BPH. This method, which ensures prolonged therapeutic effects of SLD, is intended to decrease dosing frequency and improve treatment outcomes, leading to better patient adherence. Methods: An appropriate solvent with favorable PLGA solubility, viscosity, and in vitro release profile was selected. Additionally, an I-optimal design was employed as an optimization technique. An in vivo study in albino male rats was conducted to investigate prostate-specific antigens (PSAs), prostate weight and prostatic index, histopathology, and SLD pharmacokinetics. Results: The optimized formulation showed experimental values of 29.25% for the initial burst after 2 h and 58.23% for the cumulative release of SLD after 10 days. Pharmacokinetic data revealed that the SLD–ISFI formulation had lower C_max and higher AUC values than subcutaneous (SC) pure SLD and oral commercial SLD capsule, indicating the controlled-release impact and improved bioavailability of the ISFI systems. SLD–ISFI produced a marked drop in the prostatic index by 2.09-fold compared to the positive control. Serum PSA level decreased significantly from 0.345 ± 0.007 to 0.145 ± 0.015 ng/mL after SLD–ISFI injection compared to the positive control. Conclusions: This study indicated that the optimized SLD–ISFI formulation proved its efficacy in managing BPH. Full article

Eye disorders affect a substantial portion of the global population, yet the availability of efficacious ophthalmic drug products remains limited. This can be partly ascribed to a number of factors: (1) inadequate understanding of physiological barriers, treatment strategies, drug and polymer properties, and delivery systems; (2) challenges in effectively delivering drugs to the anterior and posterior segments of the eye due to anatomical and physiological constraints; and (3) manufacturing and regulatory hurdles in ocular drug product development. The present review discusses innovative ocular delivery and treatments, encompassing implants, liposomes, nanoparticles, nanomicelles, microparticles, iontophoresis, in situ gels, contact lenses, microneedles, hydrogels, bispecific antibodies, and gene delivery strategies. Furthermore, this review also introduces advanced manufacturing technologies such as 3D printing and hot-melt extrusion (HME), aimed at improving bioavailability, reducing therapeutic dosages and side effects, facilitating the design of personalized ophthalmic dosage forms, as well as enhancing patient compliance. This comprehensive review lastly offers insights into digital healthcare, market trends, and industry and regulatory perspectives pertaining to ocular product development. Full article

Stem cell-based therapy holds promise for cartilage regeneration in treating knee osteoarthritis (KOA). Injectable hydrogels have been developed to mimic the extracellular matrix (ECM) and facilitate stem cell growth, proliferation, and differentiation. However, these hydrogels face limitations such as poor mechanical strength, inadequate biocompatibility, and suboptimal biodegradability, collectively hindering their effectiveness in cartilage regeneration. This study introduces an injectable, biodegradable, and self-healing hydrogel composed of chitosan–PEG and PEG–dialdehyde for stem cell delivery. This hydrogel can form in situ by blending two polymer solutions through injection at physiological temperature, encapsulating human adipose-derived stem cells (hADSCs) during the gelation process. Featuring a 3D porous structure with large pore size, optimal mechanical properties, biodegradability, easy injectability, and rapid self-healing capability, the hydrogel supports the growth, proliferation, and differentiation of hADSCs. Notably, encapsulated hADSCs form 3D spheroids during proliferation, with their sizes increasing over time alongside hydrogel degradation while maintaining high viability for at least 10 days. Additionally, hADSCs encapsulated in this hydrogel exhibit upregulated expression of chondrogenic differentiation genes and proteins compared to those cultured on 2D surfaces. These characteristics make the chitosan–PEG/PEG–dialdehyde hydrogel–stem cell construct suitable for direct implantation through minimally invasive injection, enhancing stem cell-based therapy for KOA and other cell-based treatments. Full article

Implantable drug delivery systems formed upon injection offer a host of advantages, including localized drug administration, sustained release, minimized side effects, and enhanced patient compliance. Among the various techniques utilized for the development of in situ forming drug implants, solvent-induced phase inversion emerges as a particularly promising approach. However, synthetic polymer-based implants have been associated with undesirable effects arising from polymer degradation. In response to this challenge, a novel category of drug delivery systems, known as phospholipids-based phase separation gels (PPSGs), has emerged. These gels, characterized by their low initial viscosity, exhibit injectability and undergo rapid transformation into in situ implants when exposed to an aqueous environment. A typical PPSG formulation comprises biodegradable components, such as phospholipids, pharmaceutical oil, and a minimal amount of ethanol. The minimized organic solvents in the composition show good biocompatibility. And the relatively simple composition holds promise for industrial-scale manufacturing. This comprehensive review provides an overview of the principles and advancements in PPSG systems, with specific emphasis on their suitability as drug delivery systems for a wide range of active pharmaceutical ingredients (APIs), spanning from small molecules to peptides and proteins. Additionally, we explore the critical parameters and underlying principles governing the formulation of PPSG-based drug delivery strategies, offering valuable insights on optimization strategies. Full article

Additively manufactured implants, surgical guides, and medical devices that would have direct contact with the human body require predictable behaviour when stress is applied during their standard operation. Products built with Fused Filament Fabrication (FFF) possess orthotropic characteristics, thus, it is necessary to determine the properties that can be achieved in the XY- and Z-directions of printing. A concentration of 10 wt% of hydroxyapatite (HA) in polyetherketoneketone (PEKK) matrix was selected as the most promising biomaterial supporting cell attachment for medical applications and was characterized with an Ultimate Tensile Strength (UTS) of 78.3 MPa and 43.9 MPa in the XY- and Z-directions of 3D printing, respectively. The effect of the filler on the crystallization kinetics, which is a key parameter for the selection of semicrystalline materials suitable for 3D printing, was explained. This work clearly shows that only in situ crystallization provides the ability to build parts with a more thermodynamically stable primary form of crystallites. Full article

The development of bone-filling biomaterials capable of delivering in situ bone growth promoters or therapeutic agents is a key area of research. We previously developed a biomaterial constituting biphasic calcium phosphate (BCP) microparticles embedded in an autologous blood or plasma clot, which induced bone-like tissue formation in ectopic sites and mature bone formation in orthotopic sites, in small and large animals. More recently, we showed that activated carbon (AC) fiber cloth is a biocompatible material that can be used, due to its multiscale porosity, as therapeutic drug delivery system. The present work aimed first to assess the feasibility of preparing calibrated AC microparticles, and second to investigate the properties of a BCP/AC microparticle combination embedded in a plasma clot. We show here, for the first time, after subcutaneous (SC) implantation in mice, that the addition of AC microparticles to a BCP/plasma clot does not impair bone-like tissue formation and has a beneficial effect on the vascularization of the newly formed tissue. Our results also confirm, in this SC model, the ability of AC in particle form to adsorb and deliver large molecules at an implantation site. Altogether, these results demonstrate the feasibility of using this BCP/AC/plasma clot composite for bone reconstruction and drug delivery. Full article

Aseptic loosening is the dominant failure mechanism in contemporary knee replacement surgery, but diagnostic techniques are poorly sensitive to the early stages of loosening and poorly specific in delineating aseptic cases from infections. Smart implants have been proposed as a solution, but incorporating components for sensing, powering, processing, and communication increases device cost, size, and risk; hence, minimising onboard instrumentation is desirable. In this study, two wireless, battery-free smart implants were developed that used passive biotelemetry to measure fixation at the implant–cement interface of the tibial components. The sensing system comprised of a piezoelectric transducer and coil, with the transducer affixed to the superior surface of the tibial trays of both partial (PKR) and total knee replacement (TKR) systems. Fixation was measured via pulse-echo responses elicited via a three-coil inductive link. The instrumented systems could detect loss of fixation when the implants were partially debonded (+7.1% PKA, +32.6% TKA, both p < 0.001) and fully debonded in situ (+6.3% PKA, +32.5% TKA, both p < 0.001). Measurements were robust to variations in positioning of the external reader, soft tissue, and the femoral component. With low cost and small form factor, the smart implant concept could be adopted for clinical use, particularly for generating an understanding of uncertain aseptic loosening mechanisms. Full article

In modern pharmaceutical technology, modified-release dosage forms, such as in situ formed implants, are gaining rapidly in popularity. These dosage forms are created based on a configurable matrix consisting of phase-sensitive polymers capable of biodegradation, a hydrophilic solvent, and the active substance suspended or dissolved in it. The most used phase-sensitive implants are based on a biocompatible and biodegradable polymer, poly(DL-lactide-co-glycolide) (PLGA). Objective: This systematic review examines the reasons for the phenomenon of active ingredient “burst” release, which is a major drawback of PLGA-based in situ formed implants, and the likely ways to correct this phenomenon to improve the quality of in situ formed implants with a poly(DL-lactide-co-glycolide) matrix. Data sources: Actual and relevant publications in PubMed and Google Scholar databases were studied. Study selection: The concept of the review was based on the theory developed during literature analysis of 12 effectors on burst release from in situ forming implants based on PLGA. Only those studies that sufficiently fully disclosed one or another component of the theory were included. Results: The analysis resulted in development of a systematic approach called the “12 Factor System”, which considers various constant and variable, endogenous and exogenous factors that can influence the nature of ‘burst release’ of active ingredients from PLGA polymer-based in situ formed implants. These factors include matrix porosity, polymer swelling, LA:GA ratio, PLGA end groups, polymer molecular weight, active ingredient structure, polymer concentration, polymer loading with active ingredients, polymer combination, use of co-solvents, addition of excipients, and change of dissolution conditions. This review also considered different types of kinetics of active ingredient release from in situ formed implants and the possibility of using the “burst release” phenomenon to modify the active ingredient release profile at the site of application of this dosage form. Full article