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.

Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for materials with inherent antibacterial activity able to replace the use of antibiotics, and in this context, hydrogels have emerged as a promising strategy. Herein, we introduce the next generation of cationic hydrogels with antibacterial activity and high versatility that can be cured on demand in less than 20 s using thiol-ene click chemistry (TEC) in aqueous conditions. The approach capitalizes on a two-component system: (i) telechelic polyester-based dendritic-linear-dendritic (DLDs) block copolymers of different generations heterofunctionalized with allyl and ammonium groups, as well as (ii) polyethylene glycol (PEG) cross-linkers functionalized with thiol groups. These hydrogels resulted in highly tunable materials where the antibacterial performance can be adjusted by modifying the cross-linking density. Off-stoichiometric hydrogels showed narrow antibacterial activity directed toward Gram-negative bacteria. The presence of pending allyls opens up many possibilities for functionalization with biologically interesting molecules. As a proof-of-concept, hydrophilic cysteamine hydrochloride as well as N-hexyl-4-mercaptobutanamide, as an example of a thiol with a hydrophobic alkyl chain, generated three-component networks. In the case of cysteamine derivatives, a broader antibacterial activity was noted than the two-component networks, inhibiting the growth of Gram-positive bacteria. Additionally, these systems presented high versatility, with storage modulus values ranging from 270 to 7024 Pa and different stability profiles ranging from 1 to 56 days in swelling experiments. Good biocompatibility toward skin cells as well as strong adhesion to multiple surfaces place these hydrogels as interesting alternatives to conventional antibiotics.

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.

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.

There is an overwhelming demand for new scaffolding materials for tissue engineering (TE) purposes. Polymeric scaffolds have been explored as TE materials; however, their high glass transition state (T<inf>g</inf>) limits their applicability. In this study, a novel materials platform for fabricating TE scaffolds is proposed based on solvent-free two-component heterocyclic triazine-trione (TATO) formulations, which cure at room temperature via thiol-ene/yne photochemistry. Three ester-containing thermosets, TATO-1, TATO-2, and TATO-3, are used for the fabrication of TE scaffolds including rigid discs, elastic films, microporous sponges, and 3D printed objects. After 14 days’ incubation the materials covered a wide range of properties, from the soft TATO-2 having a compression modulus of 19.3 MPa and a T<inf>g</inf> of 30.4 °C to the hard TATO-3 having a compression modulus of 411 MPa and a T<inf>g</inf> of 62.5 °C. All materials exhibit micro- and nano-surface morphologies suited for bone tissue engineering, and in vitro studies found them all to be cytocompatible, supporting fast cell proliferation while minimizing cell apoptosis and necrosis. Moreover, bone marrow-derived mesenchymal stem cells on the surface of the materials are successfully differentiated into osteoblasts, adipocytes, and neuronal cells, underlining the broad potential for the biofabrication of TATO materials for TE clinical applications.

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.

Metals plates and screws are the gold standard in metacarpal and phalangeal fracture fixation as they provide high stability to complex fractures. However, incidence rates of complications ranging from 42 to 92 % have been reported. Bone bioadhesive fixation based on light-cured thiol-ene technology and reinforced with hydroxyapatite (HA) is a promising solution for customizable devices with tailored mechanical properties and reduced soft tissue adhesion. The reinforcement of these thiol-ene composites with 2D textiles or meshes has been proposed; however, their role in the mechanical performance has not been explored. In this study, structural and mechanical behavior properties of a light-cured resin composite with thiol-ene precursors and HA in the presence and absence of one and three-layer of poly(ethylene terephthalate) (PET) meshes were assessed. The lack of effect of the meshes on the light-cure efficiency and the structural homogeneity of the cured composite is shown using Raman spectroscopy, water uptake measurements, and micro-computed tomography. The insertion of meshes increased the strength and energy to fracture of resin-based composite. The woven geometry of the PET meshes enables frictional sliding behavior, and reduced crack propagation ensuring integrity after matrix failure. This effect increases with the number of meshes and was significantly higher in bending than in tensile stress conditions. Related to hand and wrist fractures, the design of composite fixation devices, based on HA and meshes fillers can significantly increase the strength and toughening of those medical devices with a potential impact on post-operation by reducing mechanical mismatch of stress shielding and prevent complications due to material disintegration, resulting from the compliant and personalized bone bioadhesive fixation application.

Traumatic bone fractures are often debilitating injuries that may require surgical fixation to ensure sufficient healing. Currently, the most frequently used osteosynthesis materials are metal-based; however, in certain cases, such as complex comminuted osteoporotic fractures, they may not provide the best solution due to their rigid and non-customizable nature. In phalanx fractures in particular, metal plates have been shown to induce joint stiffness and soft tissue adhesions. A new osteosynthesis method using a light curable polymer composite has been developed. This method has demonstrated itself to be a versatile solution that can be shaped by surgeons in situ and has been shown to induce no soft tissue adhesions. In this study, the biomechanical performance of AdhFix was compared to conventional metal plates. The osteosyntheses were tested in seven different groups with varying loading modality (bending and torsion), osteotomy gap size, and fixation type and size in a sheep phalanx model. AdhFix demonstrated statistically higher stiffnesses in torsion (64.64 ± 9.27 and 114.08 ± 20.98 Nmm/° vs. 33.88 ± 3.10 Nmm/°) and in reduced fractures in bending (13.70 ± 2.75 Nm/mm vs. 8.69 ± 1.16 Nmm/°), while the metal plates were stiffer in unreduced fractures (7.44 ± 1.75 Nm/mm vs. 2.70 ± 0.72 Nmm/°). The metal plates withstood equivalent or significantly higher torques in torsion (534.28 ± 25.74 Nmm vs. 614.10 ± 118.44 and 414.82 ± 70.98 Nmm) and significantly higher bending moments (19.51 ± 2.24 and 22.72 ± 2.68 Nm vs. 5.38 ± 0.73 and 1.22 ± 0.30 Nm). This study illustrated that the AdhFix platform is a viable, customizable solution that is comparable to the mechanical properties of traditional metal plates within the range of physiological loading values reported in literature.

A novel in situ customizable osteosynthesis technique, Bonevolent™ AdhFix, demonstrates promising biomechanical properties under the expertise of a single trained operator. This study assesses inter- and intra-surgeon biomechanical variability and usability of the AdhFix osteosynthesis platform. Six surgeons conducted ten osteosyntheses on a synthetic bone fracture model after reviewing an instruction manual and completing one supervised osteosynthesis. Samples underwent 4-point bending tests at a quasi-static loading rate, and the maximum bending moment (BM), bending stiffness (BS), and AdhFix cross-sectional area (CSA: mm²) were evaluated. All constructs exhibited a consistent appearance and were suitable for biomechanical testing. The mean BM was 2.64 ± 0.57 Nm, and the mean BS was 4.35 ± 0.44 Nm/mm. Statistically significant differences were observed among the six surgeons in BM (p < 0.001) and BS (p = 0.004). Throughout ten trials, only one surgeon demonstrated a significant improvement in BM (p < 0.025), and another showed a significant improvement in BS (p < 0.01). A larger CSA corresponded to a statistically significantly higher value for BM (p < 0.001) but not for BS (p = 0.594). In conclusion, this study found consistent biomechanical stability both across and within the surgeons included, suggesting that the AdhFix osteosynthesis platform can be learned and applied with minimal training and, therefore, might be a clinically viable fracture fixation technique. The variability in BM and BS observed is not expected to have a clinical impact, but future clinical studies are warranted.

Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution.