Despite advances in scaffold development, many current biomaterials suffer from limited processability or poor biological performance. To address this, we previously introduced two novel triazine-trione (TATO)-based thermosets, T-ene and T-yne, as candidates for tissue engineering applications. In the present study, we aim to comprehensively evaluate the initial cellular response of bone marrow mesenchymal stem/stromal cells (BMSC) on TATO materials and their osteogenic potential, with a particular focus on their suitability for bone tissue engineering applications. Both T-ene and T-yne demonstrated biocompatibility comparable to polycaprolactone (PCL), as assessed by in vitro cell behavior and the chorioallantoic membrane (CAM) assay. Transcriptomic profiling via RNA sequencing of BMSC cultured on the materials revealed upregulation of mitotic processes in cells on T-ene compared to T-yne and PCL. Expression profiling of 92 osteogenic genes after 14 days in osteogenic media showed distinct gene regulation patterns in BMSC on the TATO materials compared to PCL. However, osteogenic differentiation assays, such as Alkaline Phosphatase activity and Alizarin Red R staining, showed no significant differences among the groups. These results suggest that T-ene and T-yne are promising, formable, and biocompatible candidates for use in bone tissue engineering applications.

Metal plates are commonly used for the fixation of metacarpal fractures, but are associated with complications such as tendon adhesions that impair finger mobility. AdhFix, a novel osteosynthesis material, may reduce these complications, but its biomechanical performance in the metacarpal region remains untested. This study aimed to evaluate internal bending moments during postoperative rehabilitation and assess the biomechanical potential of AdhFix in treating comminuted metacarpal shaft fractures using a human cadaveric model. In five cadaveric hands, unstable shaft fractures of the second, third, and fourth metacarpals were simulated using a 3 mm osteotomy gap and stabilized with polyether ether ketone (PEEK) plates and stainless-steel cortical screws. A custom 3D-printed guide ensured accurate osteotomy and screw positioning. Tendon loading was simulated by pulling flexor digitorum profundus tendons until fingertip-to-palm contact was achieved, followed by wrist flexion using 100 N of force on the flexor carpi radialis and ulnaris tendons. Bending of the fixation was captured using stereographic imaging, and internal bending moments were calculated via finite element modeling. After removal of the PEEK plate, the procedure was repeated using AdhFix for fixation. Maximum internal bending moments were 6.14 ± 2.03 Nmm during finger flexion and 3.37 ± 1.64 Nmm during wrist flexion. AdhFix demonstrated mechanical integrity under both conditions with no observed failure. Statement of Clinical Significance: AdhFix may provide a mechanically stable alternative to conventional plates during early rehabilitation, potentially reducing tendon adhesions and preserving finger mobility.

Metal fixation is currently the standard of care for treating bone fractures surgically, as it provides ample stability to the healing bone. However, metal components have been associated with soft tissue adhesions and are generally not patient specific. A novel light-curable bone fixation method, called AdhFix, overcomes these disadvantages by allowing for in situ customizability and demonstrating a lack of soft tissue adhesions. Previous studies on this fixation technique have demonstrated the maximum bending and torsional moments in monotonic failure tests in dry conditions. However, this fixation has yet to be tested cyclically in a more physiological environment, which would represent an important step to assessing the clinical efficacy of this technology. This study aims to test the novel fixation method cyclically at relevant force levels in a controlled near-physiological environment. Midshaft osteotomies were performed on ovine proximal phalanges which were then fixated with the AdhFix osteosynthesis technique. The constructs were tested cyclically in four-point bending for 12,600 cycles, representing 6 weeks of rehabilitation, or until failure, while submerged in Ringer solution at 37°C. The samples were divided into four groups, each tested with a different peak force. The peak forces were based on safety factors (Group 1: 100x, Group 2: 150x, Group 3: 175x, Group 4: 250x) of a physiological bending moment present in a human proximal phalanx osteosynthesis during rehabilitation exercises, determined in a previous study. All samples survived at the lowest peak moment (Group 1), whereas all failed at the highest peak force (Group 4). Kaplan-Meier curves represented the survival probability as a function of the number of cycles for each group, and a log-rank test revealed that the survival curves were significantly different (p < 0.001). The difference in patch height between the failures and survivors was not statistically significant (p = 0.113), but the final cycle displacement amplitude was statistically different (p < 0.001). This study found that this novel osteosynthesis method can survive a clinically relevant number of cycles at a force level 100× the bending loads involved in typical non-weight-bearing rehabilitation exercises. Further studies are needed to confirm safety for other conditions.

A novel composite patch osteosynthesis technique (CPT) has demonstrated promising ex vivo biomechanical performance in small tubular bones. To bridge the gap toward clinical evaluations, this study compared the stability of the CPT to a stainless-steel locking plate (LP) in an experimental in vivo ovine bilateral proximal phalanx fracture model. Eight sheep underwent a midline osteotomy with a 4.5 mm circular unicortical defect in the lateral proximal phalanx of both front limbs, treated with the CPT (n = 8) or the LP (n = 8). A half-limb walking cast, or a custom off-loading hoof shoe, was used for postoperative protection. Implant stability was assessed by post-surgery X-ray evaluations and post-euthanasia (16 weeks) dual-energy X-ray absorptiometry (DXA). At week one, all CPT implants demonstrated mechanical failure, while all LPs remained overall intact. Mean BMD was 0.45 g/cm² for CPT and 0.60 g/cm² for LP in the fracture area (p = 0.078), and 0.37 g/cm² vs. 0.41 g/cm² in the distal epiphysis (p = 0.016), respectively. In conclusion, the CPT demonstrated indications of inferior stability compared to the LP in this fracture model, which may limit its clinical applicability in weight-bearing or high-load scenarios and in non-compliant patients.

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.

Objective: To compare the biomechanical properties of using a novel composite construct (AdhFix) to an interfragmentary Kirschner wire or a reconstruction plate as adjunctive epicondylar stabilization in simulated lateral unicondylar humeral fractures.

Study design: Cadaveric biomechanical assessment.

Sample population: Paired humeri harvested from skeletally mature dogs (14–41 kg), nine cadavers per group.

Methods: Simulated lateral unicondylar humeral fractures were stabilized with a transcondylar 4.5 mm cortical screw placed in lag fashion. Adjunct fixations consisting of a novel composite incorporating 2.7 mm cortical screws on one side, and either a 2.7 mm reconstruction plate or a 1.6 mm Kirschner wire on the contralateral side, were tested within paired humeri. Repaired humeri were axially loaded to failure and construct stiffness, yield load, and ultimate load were obtained from the load‐deformation curves.

Results: In pairwise comparison, yield load was significantly higher for AdhFix group compared to the pin group, p  = .016. No statistical significance was seen in the comparison between AdhFix group and the plate group, p  = .25.

Conclusion: Adhfix was mechanically superior to K‐wires, and comparable to plate fixation, for adjunctive fixation in a lateral humeral condylar model. Our results support further investigation of the novel composite for adjunct fracture fixation in lateral humeral condylar fractures.

Clinical significance: The novel composite tested may be a viable alternative for adjunct fixation of humeral condylar fractures, a technique that circumvents plate contouring.

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.