In this study, a near-infrared (NIR)-responsive hydrogel based on ethylenediamine (EDA)-functionalized Gellan Gum was developed through a simple preparation method. This hydrogel incorporates in situ synthesized polydopamine (pDA) and was loaded with first- and second-generation antimicrobial bis-MPA polyester dendrimers (TMP-G1-[Cys]6 and MP-G2-[Cys]12), bearing cysteamine hydrochloride as peripheral functional groups. The intrinsic ability of pDA to scavenge reactive oxygen species (ROS) and convert NIR light at 810 nm into heat imparted radical scavenging activity and photothermal properties to the systems. It has been demonstrated that, due to the noncovalent interactions with both GG-EDA and pDA, dendrimers are retained differently within the sample depending on their molecular weight and the number of terminal positive charges. This difference in retention influences their antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. In particular, it has been shown that the NIR-induced photothermal effect plays a crucial role in triggering the activity of the sample loaded with the most retained dendrimer, which possesses the highest number of terminal positive charges. The high physiological fluid absorption capacity makes these materials ideal for wound exudate management. In addition, their resistance to hydrolytic degradation can be exploited to reduce the frequency of dressing changes, potentially improving patient comfort. The dendrimer-loaded samples demonstrated low cytotoxicity toward human fetal dermal mesenchymal stromal cells (FD-MSCs) and human epidermal keratinocytes (HaCaT). These findings suggest that GG-EDA@pDA+TMP-G1-[Cys]6 or TMP-G2-[Cys]12 could be promising candidates for the treatment of infected skin wounds.

Bioprinting allows for the fabrication of tissue-like constructs by precise architecture and positioning of the bioactive hydrogels with living cells. This study was performed to determine the effect of very low concentrations of alginate (0.1, 0.3, and 0.5% w/v) on bioprinting of bone marrow mesenchymal stem cells (BMSC) in gelatin methacryloyl (GelMA; 5% w/v)/alginate blend. Furthermore, while GelMA was photocrosslinked in all bioprinted constructs, the effect of crosslinking alginate with calcium chloride on the physical and biological characteristics of the constructs was investigated. The inclusion of low-concentration alginate improved the viscosity and printability of the formulation as well as the compressive modulus of the hydrogels, particularly when ionically crosslinked with calcium chloride, compared with the group in that alginate was not crosslinked. However, the stability and degradability of 3D printed scaffolds that were only photocrosslinked were comparable to those that were additionally crosslinked with calcium chloride. Noteworthily, ionic crosslinking of alginate deteriorated the viability of BMSC. Morphology and growth of BMSC were improved by adding a low alginate concentration; however, ionic crosslinking of alginate affected these factors adversely. The findings of this study underscore the significance of carefully evaluating the crosslinking strategy used in conjunction with cell-laden GelMA/alginate hydrogel to achieve balanced physical and biological properties as well as less complicated post-bioprinting processing.

The standard-of-care for treating complex bone fractures includes metal screws and plates. However, their rigid, pre-shaped geometry, coupled with a lack of patient-specific customization and degradability, often results in post-surgical complications and the need for secondary surgeries. Alternatives that are adaptable, biodegradable, and versatile enough to address these limitations have become a priority for the surgical community. Injectable viscous mixtures that harden on demand into composites present a compelling solution, as they can mimic the mechanical properties of bone and conform to any fracture geometry. One promising example evaluated in preclinical trials is clickable composites based on triazine-2,4,6-trione (TATO)-based allyl and thiol monomers combined with hydroxyapatite fillers. These materials cure via visible light-induced thiol-ene coupling chemistry, providing adequate stiffness and strength for bone healing. However, the lack of degradability in these composites has limited their broader application. To overcome this limitation, we developed a new generation of TATO composites with hydrolytically degradable ester linkages and bioresorbable fillers. Offering exceptional versatility, these advanced materials can be cast into twistable films or injected to form high-strength composites. Hydrolysis testing revealed a 41%-64% increase in mass loss compared to the non-degradable TATO composites, while maintaining a high flexural modulus up to 6.4 GPa and a softening temperature above 45 degrees C, well above body temperature. When evaluated as fracture fixation patches, the degradable composites demonstrated superior performance, including greater load capacity and flexibility, compared to their non-degradable counterparts. By delivering strong mechanical support throughout the bone healing process and seamlessly degrading over time, these composites can indeed pave the way for a new era in orthopedic care, where versatile, biodegradable materials not only address critical clinical challenges but also set a visionary standard for the future of patient-centered surgical solutions.

Sealing wet porous membranes is a major challenge when fabricating cell encapsulation devices. Herein, we report the development of an Autoclavable Transparent Thermal Cutter (ATTC) for reliably sealing wet nanofibrous membranes. Notably, the ATTC is autoclavable and transparent, thus enabling in situ visualization of the sealing process in a sterile environment and ensuring an appropriate seal. In addition, the ATTC could generate smooth, arbitrary-shaped sealing ends with excellent mechanical properties when sealing PA6, PVDF, and TPU nanofibrous tubes and PP microporous membranes. Importantly, the ATTC could reliably seal wet nanofibrous tubes, which can shoulder a burst pressure up to 313.2 +/- 19.3 kPa without bursting at the sealing ends. Furthermore, the ATTC sealing process is highly compatible with the fabrication of cell encapsulation devices, as verified by viability, proliferation, cell escape, and cell function tests. We believe that the ATTC could be used to reliably seal cell encapsulation devices with minimal side effects.

Phalangeal fractures are common, particularly in younger patients, leading to a large economic burden due to higher incident rates among patients of working age. In traumatic cases where the fracture may be unstable, plate fixation has grown in popularity due to its greater construct rigidity. However, these metal plates have increased reoperation rates due to inflammation of the surrounding soft tissue. To overcome these challenges, a novel osteosynthesis platform, AdhFix, has been developed. This method uses a light-curable polymer that can be shaped in situ around traditional metal screws to create a plate-like structure that has been shown to not induce soft tissue adhesions. However, to effectively evaluate any novel osteosynthesis device, the biomechanical environment must first be understood. In this study, the internal loads in a phalangeal plate osteosynthesis were measured under simulated rehabilitation exercises. In a human hand cadaver study, a plastic plate with known biomechanical properties was used to fix a 3 mm osteotomy and each finger was fully flexed to mimic traditional rehabilitation exercises. The displacements of the bone fragments were tracked with a stereographic camera system and coupled with specimen specific finite element (FE) models to calculate the internal loads in the osteosynthesis. Following this, AdhFix patches were created and monotonically tested under similar conditions to determine survival of the novel technique. The internal bending moment in the osteosynthesis was 6.78 ± 1.62 Nmm and none of the AdhFix patches failed under the monotonic rehabilitation exercises. This study demonstrates a method to calculate the internal loads on an osteosynthesis device during non-load bearing exercises and that the novel AdhFix solution did not fail under traditional rehabilitation protocols in this controlled setting. Further studies are required prior to clinical application.

The effect of blue light on atmospheric corrosion of Cu and on the antimicrobial properties was explored upon exposure mimicking the condition of hygienic surface disinfection. The results show that blue light illumination enhanced the formation of Cu2O, resulting in a slightly increased corrosion resistance of Cu without pre-deposited NaCl, whereas the enhanced formation of Cu2O, CuCl and/or Cu(OH)3Cl on copper with pre-deposited NaCl caused concomitant corrosion product flaking and a reduced corrosion resistance. The blue light induced enhancement of Cu corrosion led to increased surface roughness and more pronounced integration of bacteria within the corrosion products.

Open reduction internal fixation metal plates and screws remain the established standard-of-care for complex fracture fixation. They, however, have drawbacks such as limited customization, soft-tissue adhesions, and a lack of degradation. Bone cements and composites are being developed as alternative fixation techniques in order to overcome these issues. One such composite is a strong, stiff, and shapeable hydroxyapatite-containing material consisting of 1,3,5-triazine-2,4,6-trione (TATO) monomers, which cures through high energy visible light-induced thiol–ene coupling (TEC) chemistry. Previous human cadaver and in vivo studies have shown that patches of this composite provide sufficient fixation for healing bone fractures; however, the composite lacks degradability. To promote degradation through hydrolysis, new allyl-functionalized isosorbide-based polycarbonates have been added into the composite formulation, and their impact has been evaluated. Three polycarbonates with allyl functionalities, located at the termini (aPC1 and aPC2) or in the backbone (aPC3), were synthesized. Composites containing 1, 3, and 5 wt % of aPCs 1–3 were formulated and evaluated with regard to mechanical properties, water absorption, hydrolytic degradation, and cytotoxicity. Allyl-functionalized polycaprolactone (aPCL) was synthesized and used as a comparison. When integrated into the composite, aPC3 significantly impacted the material’s properties, with the 5 wt % aPC3 formulation showing a significant increase in degradation of 469%, relative to the formulation not containing any aPCs after 8 weeks’ immersion in PBS, along with a modest decrease in modulus of 28% to 4.01 (0.3) GPa. Osteosyntheses combining the aPC3 3 and 5 wt % formulations with screws on synthetic bones with ostectomies matched or outperformed the ones made with the previously studied neat composite with regard to bending stiffness and strength in four-point monotonic bending before and after immersion in PBS. The favorable mechanical properties, increased degradation, and nontoxic characteristics of the materials present aPC3 as a promising additive for the TATO composite formulations. This combination resulted in stiff composites with long-term degradation that are suitable for bone fracture repair.

Infected skin wounds represent a serious health threat due to the long healing process and the risk of colonization by multi-drug-resistant bacteria. Silver nanoparticles (AgNPs) have shown broad-spectrum antimicrobial activity. This study introduces a novel approach to address the challenge of infected skin wounds by employing gellan gum-dopamine (GG-DA) as a dual-functional agent, serving both as a reducing and capping agent, for the in situ green synthesis of silver nanoparticles. Unlike previous methods, this work utilizes a spray-drying technique to convert the dispersion of GG-DA and AgNPs into microparticles, resulting in nano-into-micro systems (AgNPs@MPs). The microparticles, with an average size of approximately 3 μm, embed AgNPs with a 13 nm average diameter. Furthermore, the study explores the antibacterial efficacy of these AgNPs@MPs directly and in combination with other materials against gram-positive and gram-negative bacteria. The versatility of the antimicrobial material is showcased by incorporating the microparticles into injectable hydrogels. These hydrogels, based on oxidized Xanthan Gum (XGox) and a hyperbranched synthetic polymer (HB10K-G5-alanine), are designed with injectability and self-healing properties through Shiff base formation. The resulting nano-into-micro-into-macro hybrid hydrogel emerges as a promising biomedical solution, highlighting the multifaceted potential of this innovative approach in wound care and infection management.

Hydrogel-based localised drug delivery minimises systemic side effects and a linear release profile ensuring a sustained drug release over time, crucial for long-term therapy. The current paper describes the use of the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAc) to append azidified Dexamethasone (Dex) onto dendrons of first- and second-generation PEGs. Crosslinking with thiolated PEGs using either thiol-acrylate or nucleophilic addition reactions yielded gels containing β-thio-ether ester groups that imparted enhanced hydrolytic susceptibility. In vitro gel degradation was followed gravimetrically and expressed as swelling ratios. Thiol-acrylate crosslinked hydrogels exhibited zero-order Dex release kinetics over 11, 27, and 16 days (G1, G1-star, and G2). Crosslinking the G1-gels by nucleophilic addition also resulted in linear release and the end point was reached in 5 days. Hydrolysis was accounted as the main release mechanism for covalently bound Dex, while physically incorporated Dex showed undefined rapid burst or first-order release, with most of the drug released in the initial 1–3 days. Eluates from covalently bound Dex maintained high activity, whereas Trap-Dex gels lost activity over time, as detected by the upregulation of luciferase expression from a transformed cell line. This novel chemistry combination offers precise drug release control applicable beyond Dex to drugs with suitable nucleophilic groups.

Heterofunctional polyester dendrimers up to the third generation, containing 21 internally queued bromine atoms, have been successfully synthesized for the first time using a divergent growth approach. Direct azidation reactions enabled the conversion of the bromide groups to clickable azide pendant functionalities. Therapeutic and chemical moeities could then be coupled to the internal azide or bromide functionalities and external hydroxyl groups of the heterofunctional dendrimers through CuAAC, thiol-bromo click and esterification reactions, expanding their potential for biomedical applications.