The human meniscus transmits high axial loads through the knee joint. This function is compromised upon meniscus injury or treatment by meniscectomy. 3D printing of meniscus implants has emerged as a promising alternative treatment, as it allows for precise mimicry of the meniscus architecture. In this study, silk fibroin (SF) known for its excellent mechanical properties is used to fabricate hydrogels for 3D bioprinting with infrapatellar fat pad-derived mesenchymal stem cells (IFP-MSCs). Extracellular matrix (ECM) derived from bovine menisci and gelatin are added to 10% SF to promote cell adhesion and printability. To examine the mutual influence of cells and biomaterial, experiments are conducted with and without IFP-MSCs. The cells are found to influence crosslinking, β-sheet formation, and mechanical strength. Variations between printed and casted hydrogels are identified for cell number, metabolic activity, secondary structure, and mechanical strength. Remarkably, the printed hydrogels with IFP-MSCs exhibited a compressive Young's modulus of 0.16 MPa, which closely resembled that of human osteoarthritic menisci. After initial low viability, IFP-MSCs in the casted hydrogels are able to proliferate within the biomaterial. The chondrogenic differentiation medium upregulated the expression of chondrogenic markers in the casted hydrogels, indicating promising prospects for future meniscus tissue engineering (TE).

Mucoadhesive films are attractive for buccal drug delivery because of their extended retention on the mucosal surface, enabling sustained drug delivery to and across the tissue. In this study, poly(2-hydroxyethyl ethyleneimine) (P2HEEI) was synthesized by reacting linear polyethyleneimine (L-PEI) with 2-bromoethanol and combined with chitosan to formulate mucoadhesive films for buccal delivery of haloperidol. The polymer displayed excellent solubility in water, a low glass transition temperature (-31.6 °C) and low toxicity in human dermal skin fibroblast cells. This polymer was then blended with chitosan before films were formed by a casting technique. Differential scanning calorimetry and scanning electron microscopy confirmed that chitosan and P2HEEI were fully miscible in the blends. The films based on chitosan-P2HEEI blends were more elastic and had enhanced mechanical properties. Films containing haloperidol were also formulated. The release of haloperidol from the films increased as the P2HEEI content in the blends was raised. Mucoadhesion of these films on ex vivo sheep buccal mucosal tissues was evaluated using a tensile method. All films were mucoadhesive but increasing P2HEEI content in the blend gradually reduced adhesion to the buccal mucosa.

Magnetic particle imaging (MPI) is a promising imaging modality nearing clinical introduction. MPI's tracer-based principle allows for highly sensitive background-free imaging. Potential clinical applications include cardiovascular imaging and endovascular interventions. In principle, medical instruments are invisible in MPI due to the missing signal generation. Therefore, permanent marking technologies have been introduced. Additionally, temporary markers are of interest for follow-up examinations after stent implantation to prevent artifacts during postinterventional stent lumen quantification. Consequently, medical instrument markers for MPI, based on biodegradable polylactic acid (PLA) and superparamagnetic iron-oxide nanoparticles (SPIONs), are developed in this study. To investigate the markers, signal characteristics and degradation over time are studied for 28 d in a water bath at 37 °C. The samples are analyzed using a scale, micro-CT, microscopy, magnetic particle spectroscopy (MPS), MPI, and vibrating sample magnetometry (VSM). A continuous mass decrease is detected (≈90% after 28 d), while MPS and MPI data show no loss of signal. VSM confirms that the markers' mass reduction can be accounted for the degradation of PLA, while the SPIONs hardly detach from the coating. The introduced marking technology, with its degradation characteristics and signal behavior, is the basis for a variety of anticipated medical application scenarios.

Conjugated polymers (CPs) with rigid hydrophobic backbones and polar side chains are known for their efficient cellular entry using various endocytic pathways. Here, the efficient delivery of ribonuclease A (RNase A) into the cytosol of a model cancer cell using a charge-neutral CP with phenyl carbamoylated guanidine (Ph-CG) group at the end of a short ethylene oxide side chain is described. This unique combination of the hydrophobic backbone and the polar nonionic side chain facilitates efficient protein complex formation and subsequent cellular entry through a non-lysosomal pathway, leading to concentration-dependent cell viability inhibition at a half-maximal effective concentration of 0.07 µg mL (or 5 nm). This work demonstrates the potential of CPs as carriers for intracellular protein delivery and the importance of the end functional group of protein carriers.

The most recent advances in bone tissue engineering (BTE) approaches step forward in the field of three-dimensional (3D) tissue models, enabling the development of more realistic tools to study bone disorders, such as osteoporosis. BTE field aims to mimic native bone tissue more truthfully, providing an appropriate environment for tissue regeneration and repair through the combination of 3D porous scaffolds, specific growth factors, and cells. Currently, the scientific community is focused on developing and improving new biomaterials that in combination with growth factors and specific cell types, that can accurately emulate the native bone microenvironment. However, most of the reported studies in the BTE field are focused on bone formation, disregarding the entire bone remodeling steps, which also involve bone resorption. In this review, the currently available mono and co-culturing methods, types of biomaterials used in several strategies that combine scaffolds and relevant cells (e.g., osteoblasts (OBs), osteoclasts (OCs), and osteocytes (OCys)), envisioning a healthy bone formation and remodeling process, the gold-standard drug delivery systems, and bioengineered-based systems to tackle bone diseases are described.

Surgical success relies on precise tissue approximation using sutures, clips, or staples. Fibrin sealant provides a user-friendly alternative, saving time and maintaining tissue integrity. Yet, its cost and potential bioburden risk are notable drawbacks. To address these concerns, a semi-autologous fibrin sealant is produced from human cryoprecipitate and compared it to a commercial fibrin sealant. The microstructure of the semi-autologous sealant closely resembles the commercial one. Initially, the commercial sealant has superior bonding strength, however, over time, both demonstrate strong adhesive properties. Moreover, when the two sealants contain equivalent fibrinogen concentrations, they show similar bonding strength and rheological properties, including thixotropic behavior, which is essential for their application as bioadhesives. Notably, it is discovered that the mechanical properties of the adhesive are mainly governed by the fibrinogen concentration, with minimal impact of other blood components. This understanding paves the way for the development of an efficient method to boost fibrinogen in blood without extensive separation. This study indicates semi-autologous fibrin glue matches commercial sealant in adhesive properties. This may offer several advantages, such as reduced bioburden, costs, improved immunomodulation, and reduced hypersensitivity and virus transmission risks. These findings hold promising prospects for enhancing the wound healing process in various medical conditions.

In this study, a substrate-independent maleimide film is developed that can be formed under mild aqueous conditions (pH 7.4), and which allows rapid and efficient external thiol immobilization onto the coated surfaces. For the coating block, tyrosine-conjugated maleimide (Tyr-Mal) containing a phenolic amine moiety is prepared as a substrate-independent dormant coating precursor, wherein the maleimide component permits a rapid Michael addition reaction with the thiol moiety of interest. By mimicking natural melanogenesis, Tyr-Mal acts as a substrate for tyrosinase under physiological conditions (pH 7.4) to form a melanin-inspired maleimide (Mel-Mal) film on various substrates, including living cell surfaces. The resulting film undergoes a rapid surface reaction (< 30 min) with external thiol groups under mild aqueous conditions. Considering that a typical polydopamine film requires a long reaction time (≈3 h) under alkaline conditions (pH 8.5) to achieve thiol functionalization with low efficiency, the current surface platform demonstrates significant improvements in terms of its reaction kinetics and usability. Moreover, considering that thiol functionalization and surface coating are performed under mild aqueous conditions, it is expected that the developed Mel-Mal film will be a useful tool in the fields of cell surface engineering, microarrays, and high-throughput screening.

An integrated strategy that combines innovative electrospinning technique with traditional hot-stretching post-treatment is designed and implemented to generate high-molecular-weight poly(l-lactic-acid) (hmwPLLA, Mw = 2 80 000 Da) electrospun nanofiber-constructed yarns (ENCYs). The internal fiber diameter within the hmwPLLA ENCYs is found to increase gradually with the increase of hmwPLLA solution concentration. The hmwPLLA ENCY generated from a concentration of 10% (w v) is demonstrated with uniform morphology with an average fiber diameter of 737.7 ± 72.2 nm and an average yarn diameter of 454.9 ± 3.5 µm. Compared with the unstretched hmwPLLA ENCY, increasing the hot-stretching temperature can significantly enhance the fiber orientation and crystallinity. Moreover, the mechanical properties of stretched ENCYs are obviously enhanced compared with the unstretched control. The fiber orientation and crystallinity of stretched ENCYs are also found to be significantly improved with the increase of hot stretching rate, further resulting in the obvious increase of breaking strength and Young's modulus. Importantly, the braided textiles made from stretched hmwPLLA ENCYs exhibited great biocompatibility by effectively guiding the cell alignment and supporting the cell adhesion and proliferation. In summary, the high performance hmwPLLA ENCYs show great potential for the future design and development of advanced biomedical textiles.

PVA has emerged as a prevalent material for the construction of vascular tissue engineering scaffolds. Nonetheless, the integration of 3D crosslinked polyvinyl alcohol (PVA) scaffolds featuring arginine-glycine-aspartate (RGD) binding remains a rarity in tissue engineering. In the present study, a PVA-4-azidobenzoic acid (AZ)-RGD scaffold is prepared based on cross-linking of two distinct PVA derivatives: one featuring photoreactive azides for ultraviolet (UV)-crosslinking and the other incorporating RGD peptides. The results show that the PVA-AZ-RGD scaffold has good blood compatibility and biomechanical properties, with hydrophilic properties, and a hydrolysis rate of 27.31% at 12 weeks. Notably, the incorporation of RGD peptides significantly bolsters the attachment and proliferation of mesenchymal stem cells (MSCs) on the scaffolds, compared to non-RGD-conjugated controls. Furthermore, RGD conjugation markedly accelerates endothelialization of MSCs following 15 days of endothelial culture. Post-transplantation, the PVA-AZ-RGD scaffold exhibits favorable blood flow patency, minimal immune rejection, promotes endothelialization and smooth muscle cell proliferation, and facilitates the development of extracellular matrix, ultimately contributing to the formation of regenerative artificial blood vessels. These comprehensive findings underscore the promising potential of RGD-integrated, crosslinked PVA scaffolds for applications in vascular tissue engineering.

Pelvic organ prolapse (POP) affects many women, especially after menopause. POP occurs due to the descent of weakened supportive tissue. Current prolapse surgeries have high failure rates, due to disturbed wound healing caused by lower tissue regeneration and estrogen depletion. Absorbable poly-4-hydroxybutyrate (P4HB) knit implants exhibited improved cell and tissue response leading to less complications from prolapse surgery. This study aims to enhance wound healing and improve surgical outcomes by using an electrospun (ES) P4HB scaffold (ES P4HB) that emulates natural tissue structure. Further 17β-estradiol (E2)-a prominent wound healing factor-is incorporated into the scaffold (ES P4HB-E2). Parous Dohne Merino sheep underwent posterior vaginal wall implantation of either P4HB (n = 6) or 17β-estradiol relasing P4HB-E2 (n = 6) scaffolds, or underwent native tissue repair (NTR) (n = 4). Vaginal explants were compared for short-term host response in terms of gross necropsy, histomorphology, biomechanics, tissue-integration, and degradation of P4HB at 3-months post-implantation. Both scaffolds show promising results with enhanced mechanical properties and increased macrophage infiltration compared to NTR, but without differences between scaffolds. Thus, it seems electrospun P4HB scaffolds already improve tissue integration and healing. Further long-term studies are needed before these scaffolds can be used in clinical practice.

Oral insulin delivery systems are currently being explored as the best alternative to subcutaneous injections, aiming to overcome gastrointestinal barriers and achieve efficient oral insulin delivery. This study presents a microemulsion delivery system that utilizes chitosan/sodium tripolyphosphate (CS/STPP) to enhance the stability of kernel-loaded insulin and increase bioavailability via intestinal absorption and lymphatic transport. The insulin/chitosan/sodium tripolyphosphate-microemulsion (Ins/CS/STPP-ME) is a particle size of (81.03 ± 7.19) nm and a polydispersity index (PDI) of (0.313 ± 0.013). Infrared spectroscopy confirms insulin encapsulation. Ins/CS/STPP-ME exhibits favorable stability and releasesproperties in gastrointestinal fluids, retaining a maximum of (53.076 ± 12.587)% insulin in a pepsin environment and (62.982 ± 13.105)% in a trypsin environment after 60 min. In vivo studies have demonstrated that the addition of CS/STPP to the internal phase of Ins/CS/STPP-ME results in a rapid onset of action and sustained hypoglycaemic effect in diabetic rats. Lymphatic blockade by cycloheximide verified Ins/CS/STPP-ME and its ability to cross the gut and enter the bloodstream via lymphatic transport. This work demonstrates that Ins/CS/STPP-ME can stabilize proteins in the gastrointestinal environment, facilitate lymphatic absorption, enhance bioavailability, and provide longer-lasting hypoglycemic effects, thus providing the possibility for oral biomacromolecule delivery.

Current treatments for bone injuries face notable limitations such as adverse reactions to implant materials and increased risks of infection. There is an essential need for a therapeutic that will address these issues and decrease recovery times. Herein, a multifunctional nanohybrid zinc-based metal-organic framework integrated with gold nanoparticles (Au@ZIF-8) is synthesized to promote antibacterial and osteogenic benefits. Au@ZIF-8 is capable of converting light energy into heat and has demonstrated its ability to increase the surrounding temperature by ≈30 °C. As a result, Au@ZIF-8 has exhibited bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) upon exposure to near-infrared (NIR) irradiation. Concurrently, Au@ZIF-8 sustains the release of zinc ions from the nanohybrid for the potential of bone repair. When combined with a gelatin-based hydrogel, Au@ZIF-8 significantly elevated osteogenic gene expression and promoted preosteoclast differentiation through the sustained zinc ion release, as opposed to a gel-only control. The potential of the multifunctional nanohybrid is further demonstrated as a coating material for titanium orthopedic implants to introduce antibacterial properties and promote osteogenic differentiation of preosteoblasts for bone healing. Given its excellent antibacterial in response to NIR irradiation and osteogenic abilities, Au@ZIF-8 is a promising photothermal therapy for bone injuries.

Dermatological diseases represent one of the most prevalent health concerns globally, with associated care and treatment costs having consistently increased over the past decade. Current therapeutic modalities, including topical medications, oral pharmaceuticals, and physical therapies, frequently face challenges such as inadequate drug absorption and substantial adverse effects. Microneedles, recognized as minimally invasive drug delivery systems, effectively penetrate the cutaneous barrier to enhance drug permeability and therapeutic efficacy. Polyphenols-abundant in botanical and marine sources-demonstrate diverse pharmacological properties encompassing anti-inflammatory and antioxidant activities. The integration of polyphenols with microneedle technology has emerged as a promising therapeutic strategy for dermatological conditions, demonstrating significant clinical potential. This review examines the multifunctional capabilities of polyphenol-incorporated microneedles and elucidates their mechanisms of action in managing dermatological disorders. Furthermore, it synthesizes recent progress in polyphenol-based microneedle applications for various cutaneous pathologies, including acne vulgaris, psoriasis, and atopic dermatitis. Finally, current challenges is discussed and proposed future research directions for optimizing polyphenol microneedle systems in dermatological therapeutics.

Efficient intracellular protein delivery is of great importance for the development of protein-based therapy and modern biotechnologies. However, the hydrophilic and macromolecular nature of proteins greatly hinders their ability to cross cell membranes. Herein, a calixarene modification strategy for the intracellular delivery of protein drugs is developed. The decoration of sulfonate azocalix[4]arene (SAC4A) on proteins results in a nano-multivalent effect between Protein-S and amino acids on the cell surface, leading to efficient intracellular delivery of the protein via the clathrin-mediated endocytic pathway. By using SAC4A as a novel ligand, this calixarene modification strategy efficiently delivers 7 proteins, bovine serum albumin (BSA), trypsin (TRY), horseradish peroxidase (HRP), α-chymotrypsin (α-Chyt), lysozyme (LYZ), cytochrome C (Cyt C) and ribonuclease A (RNase A), into cells and significantly enhances the cytotoxicity of Cyt C and RNase A. Moreover, SAC4A-modified Cyt C demonstrates markedly enhanced antitumor efficacy in 4T1-bearing mice without notable side effects. Considering that these proteins are varied in molecular weight and isoelectric point, this calixarene modification strategy provides a platform technology for intracellular protein delivery and the development of protein drugs targeting intracellular pathways.

Poly(ε-caprolactone) (PCL) is a hydrolytically degradable biopolyester used in drug delivery to enhance drug solubility and bioavailability, where drugs are typically incorporated physically within the biopolymeric matrix rather than covalently bonded, due to the limited availability of functional groups required for covalent attachment. In pursuit of developing a facile method for the production of a biopolyester-drug covalent conjugate with effective drug loading capacity, this study reports the synthesis of a covalent Silibinin-PCL conjugate (Sil-PCL) through a two-step approach. This involves the controlled hydrolysis of a high molecular weight PCL to increase the concentration of carboxylic end groups, which are subsequently used for the catalyzed esterification with Silibinin. The Sil-PCL is characterized with mass spectrometry, gel permeation chromatography, thermogravimetric analysis, differential scanning calorimetry, and NMR and UV-vis spectroscopies. The cytotoxic effects of Sil-PCL against colorectal adenocarcinoma cells (Caco-2) are measured through the MTT assay. The results of the Sil-PCL characterization revealed a Silibinin loading of ≈9.8 wt.%. The MTT assay demonstrated that Sil-PCL induced cytotoxic effects at concentrations a hundred times lower than those required for free Silibinin. The proposed approach might represent a reliable pathway for the development of biopolyester-based covalent conjugates with a high drug loading capacity.

Polymeric nanoarchitectures are crafted from amphiphilic block copolymers through a meticulous self-assembly process. The composition of these block copolymers is finely adjustable, bestowing precise control over the characteristics and properties of the resultant polymeric assemblies. These nanoparticles have garnered significant attention, particularly in the realm of biological sciences, owing to their biocompatibility, favorable pharmacokinetics, and facile chemically modifiable nature. Among the myriad of polymeric nanoarchitectures, micelles and polymersomes stand out as frontrunners, exhibiting much potential as cargo carrier systems for diverse bio-applications. This review elucidates the design strategies employed for amphiphilic block copolymers and their resultant assemblies, specifically focusing on micelles and polymersomes. Subsequently, it discusses their wide-ranging bio-applications, spanning from drug delivery and diagnostics to bioimaging and artificial cell applications. Finally, a reflective analysis will be provided, highlighting the current landscape of polymeric cargo carriers, and discussing the opportunities and challenges that lie ahead. With this review, it is aimed to summarize the recent advances in polymeric assemblies and their applications in the biomedical field.

Multicomponent self-assembly represents a cutting-edge strategy in peptide nanotechnology, enabling the creation of nanomaterials with enhanced physical and biological characteristics. This approach draws inspiration from the highly complex nature of the native extracellular matrix (ECM) constituting multicomponent biomolecular entities. In recent years, the combination of bioactive peptide with polymer has gained significant attention for the fabrication of novel biomaterials due to their inherent specificity, tunable physiochemical properties, biocompatibility, and biodegradability. This advanced strategy can address the limitation of the lower mechanical strength of the individual peptide hydrogel by incorporating the biopolymer, resulting in the formation of a composite scaffold. In this direction, this advanced strategy is explored using noncovalent interactions between cellulose nano-fiber (CNF) and cationic Cardin-motif peptide to develop advanced composite scaffolds. The bioactive cationic peptide otherwise failed to form hydrogel at physiological conditions. Interestingly, the differential mixing ratio of CNF and peptide modulated the surface charge, functionality, and mechanical properties of the composite scaffolds, resulting in diverse cellular responses. 10:1 (w/w) ratio of CNF and peptide-based composite scaffold demonstrates improved cellular survival and proliferation in 2D culture conditions. Notably, in 3D cultures, cell proliferation on the 10:1 matrix is comparable to Matrigel, highlighting its potential for advanced tissue engineering applications.

Adhesive hydrogels are emerging as attractive functional materials for various fields, such as tissue engineering, wound healing, E-skins, etc. However, the removal of adhesive hydrogels from covered area may be painful and cause a secondary damage. In the current study, gelatin-based hydrogels are prepared by cross-linking with tannic acid and 4-formylphenyl boronic acid, through simultaneous dynamic covalent boronic ester and imine bond formations. The obtained hydrogels not only present self-healing and injectable properties, but also show tunable adhesiveness that regulated by temperature and oxidation degrees of tannic acid. The maximum adhesion strength of the hydrogels with medium oxidation degree at 37 °C can be measured up to 30 kPa on porcine skin, while the value decreased to ≈10 kPa at lowered temperature of 25 °C, facilitating the unpainful removal of the hydrogels from skins. This work provides a new approach for the design of functional hydrogels with tailorable adhesiveness.

There has been limited exploration of carbon nanofiber as a scaffold for cellular attachment and proliferation. In this work, commercially available, pyrolytically stripped carbon nanofiber (cCNF) is deposited over electrospun nanofiber mats, polycaprolactone (PCL) and poly(D-lactide) (PDLA), to immobilize them and investigate whether the 3D cCNF layer's surface augments cell proliferation of human dermal fibroblasts (nHDF). Spectral characterizations, such as XRD and Raman, show that cCNF exhibited crystalline structure with a high graphitization degree. cCNF layers are modified to have an irregular or planar surface by simple agitation (s-cCNF) or probe sonication (p-cCNF) of the solution. The in vitro cell line studies revealed that p-cCNF is better than s-cCNF in providing a platform that supports a homogenous spread of the fibroblasts all over the nanofiber's surface. The p-cCNF-deposited PCL mat (p-cCNF@PCL) demonstrated cellular growth, similar to that of the neat PCL mat. However, the p-cCNF@PCL mat exhibited remarkable antibacterial properties by reducing the E. coli numbers, ≈16 times greater than the PCL mat. It is concluded that the immobilized, pyrolytically stripped carbon nanofiber's surface has the potential to accommodate cellular growth and inhibit bacterial colonies, suggesting the biomaterial scaffold is promising for in vivo and clinical applications of skin tissue regeneration.

This article explores the hierarchical self-assembly of short peptides, which refers to the structured spatial arrangements of these molecules over long distances. This phenomenon is commonly found in nature and has important implications for biological structure and function. Short peptides are preferred for self-assembly because they have the ability to spontaneously create various nanostructures. This process, known as bottom-up assembly, allows for the addition of functional groups at the carboxyl or amine ends of the peptides. These functional groups enable specific functions that are extremely valuable in the fields of biotechnology and biomedicine. This text discusses the basic processes involved in the self-assembly of short peptides, such as the characteristics of amino acid side chains, the categorization of short peptides according to their chemical structure, the influence of intermolecular forces, and the dynamic nature of the self-assembly process. In addition, the paper discusses the various uses of short peptides in the disciplines of biomedicine and optoelectronics, including stimulus-responsive hydrogels, tissue engineering, and drug delivery. The article also suggests rational design principles for controlling the hierarchical self-assembly of short peptides, creating new commercial applications, particularly with functional hydrogels, and offers insights into the future of the discipline.

Chemotherapy is generally given by intravenous (IV) administration which provides higher bioavailability than other systemic routes. However, in the case of lung cancer, the pulmonary (INH) route is the other choice for inhalable formulations. In the study, biochemical and histological parameters of Cabazitaxel (CBZ) free (2 mg kg) and nanoparticle (NP) (2 mg kg CBZ equivalent) formulations are investigated after IV and INH administration in rats. The nanoformulation of CBZ is obtained using PEGylated polystyrene (PEG-PST) nanoparticles obtained by PISA. While a nose and head-only device is used for INH administration, a jugular vein is used as the IV route. Blood samples (blank, 24 h, and 48 h) are collected via carotid artery cannulas without handling in metabolism cages. According to biochemical parameters, free CBZ formulation applied via IV or INH route shows higher systemic toxicity. On the other hand, the nanoformulation of CBZ showed no signs of toxicity in both IV or INH routes. Higher and longer retention is observed in the case of inhaled nanoformulation. Histological analysis showed higher alveolar macrophage migration for inhaled nanoformulation due to enhanced retention. Results showed that nanotechnology and the lung defense system gave the advantage to end up with an inhalable nanomedicine formulation for lung cancer.