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.

Metal plates and screws have been used as the gold standard for Open ReductionInternal Fixation (ORIF) treatments of complex bone fractures for decades.However, the drawbacks of these implants necessitate a transition towards morepatient-personalized treatments. Injectable adhesive composites that can curerapidly on demand via photopolymerization have shown great potential in tissuerepair surgeries. Such systems allow for a high level of in situ customization,which replaces the current need for surgeons to stockpile large quantities ofdifferent metal implants. The use of step growth thiol-ene coupling (TEC)chemistry to polymerize these composites allows for high monomer conversion,reducing safety concerns from the leach out of non-reacted monomers.To develop stiff and strong resins, triazinetrione (TATO) monomers werechosen to form crosslinked networks in conjunction with hydroxyapatite (HA).Degradability was introduced into the composite in two different ways. In thefirst approach, isosorbide-based polycarbonates in different weight percentageswere included in the composite formulation, resulting in improved degradationrates while surpassing the mechanical properties needed for hand rehabilitationexercises. In the second approach, the introduction of ester moieties wascombined with the partial replacement of HA with the more resorbableinorganic fillers tricalcium phosphate and bioactive glass. This led to a family ofcomposites with a wide range of degradability profiles and mechanicalproperties, highlighting the tunability of these materials.Inspired by dental composites, TATO-based primers containing allylfunctionalizedmonomers with either n-hydroxysuccinimide (NHS) orphosphonic acid (Phn) groups were developed. These monomers allowed forenhanced adhesion to bone and photopolymerization via TEC with the TATObasedcomposite, resulting in an adhesive composite patch system capable offixating bone fractures without the use of metal screws. The incorporation ofthese monomers allowed the primers to interact with collagen or hydroxyapatitepresent in the bone surface, resulting in shear strengths on bone substrates thatoutperformed existing commercially available superglues. These resultsdemonstrate how acrylate-free primers and composites can be used inbiocompatible, strong and biodegradable fixation patches, suitable for fracturefixation in non- or low-load bearing bones.

Metallplattor och skruvar har i årtionden varit guldstandarden för öppenreposition och intern fixering (ORIF) vid behandling av komplexa benfrakturer.Deras rigida geometri och mekaniska egenskaper medför dock vissa nackdelar,vilket skapar ett behov av mer patientanpassade behandlingar. Injicerbaraviskösa kemiska blandningar som kan härda med hjälp av fotokemi till starkakompositer för frakturbehandling har visat stor potential i laboratoriemiljö. Merspecifikt har styva och starka kompositbaserade implantat, baserade påtriazinetrion (TATO)-monomerer i kombination med hydroxiapatit (HA),uppvisat stor potential. Dessa system bildar tvärbundna nätverk genomljushärdande tiol-en-kopplingskemi (TEC) vilket möjliggör fullständigpolymerisation av monomerblandningar till kompositer. Kombinationen avicke-toxiska kompositer och mild kemi vid tillverkningen möjliggör en hög gradav patientanpassning, vilket i framtiden kan eliminera behovet av att sjukhusenupprätthåller stora lager av metallimplantat.Tidigare studier har visat att TATO-kompositer är icke-nedbrytbara iprekliniska tester. Kirurgernas förväntningar på framtida implantat är dockstarkt kopplade till nedbrytbara material. För att möta dessa behov utveckladestvå olika materialsystem där nedbrytbarhet integrerades. I det första systemetinkluderades nedbrytbara polykarbonater baserade på isosorbid. utveckladestvå olika materialsystem där nedbrytbarhet integrerades, samtidigt som demekaniska egenskaperna överträffade de krav som ställs förrehabiliteringsövningar, exempelvis vid fingerfrakturer. I det andra systemetutvecklades nya TATO-monomerer med hydrolytiskt känsliga esterbindningar ikombination med resorberbara fyllmedel såsom trikalciumfosfat och bioaktivtglas. Detta resulterade i en ny familj av kompositer med en bred variation avnedbrytbarhetsprofiler och mekaniska egenskaper.För att möjliggöra en fullständig ersättning av metallimplantat med adhesivakompositer utvecklades även nya primersystem som effektivt kan förankrakompositer till blött ben. Inspirerade av dentala primersystem utvecklades nyaTATO-baserade primrar, innehållande allylfunktionaliserade monomerer medantingen n-hydroxysuccinimid (NHS)- eller fosfonsyra (Phn)-grupper. Dessasystem förbättrade vidhäftningen till ben och möjliggjorde fotopolymerisationvia TEC med den TATO-baserade kompositen. De aktiva monomererna iprimersystemen interagerade med kollagen och hydroxiapatit – deIVhuvudsakliga komponenterna i ben – vilket resulterade i stark adhesion avkompositerna till bensubstrat, med skjuvhållfastheter som överträffadebefintliga kommersiellt tillgängliga superlim. Slutligen utvärderades dessasystem som adhesiva benplåster för att fixera benfrakturer utan behov avmetallskruvar. Resultaten visar att akrylatfria primers och kompositer kananvändas i biokompatibla, starka och biologiskt nedbrytbara fixeringsplåster,lämpliga för fixering av lågbelastade komplexa benfrakturer.

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.

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.

Hydroxyapatite (HA) infused triazine-trione (TATO) composites have emerged as an injectable platform for customizable bone fixators due to their fast and benign curing via high-energy visible light-induced thiol-ene chemistry (HEV-TEC), promising mechanical performance, and preclinical outcomes. These composites can overcome many of the existing limitations accompanying metal implants such as poor patient customizability, soft tissue adhesions, and stress shielding. Taking into account that the promising benchmarked TATO composite (BC) is based on stable sulfur-carbon bonds, we herein investigate the impact of introducing polyester dendritic cross-linkers based on bis-MPA as chemically integrated branched additives that display labile esters in a branched configuration. The inclusion of dendrimers, G1 and G3, in concentrations of 1, 3, and 5 wt % in the composite formulations were found to (i) decrease the processing viscosity of the composite formulations, reaching Newtonic and nonshear thinning behavior at 37 degree celsius and (ii) impact the size distribution of bubble cavities in the composite cross sections. The lowest collected T-g for the dendrimer-containing composites was noted to be 73.2 degree celsius, a temperature well above physiological temperature. Additionally, all composites displayed flexural modulus above 6 GPa and flexural strength of ca. 50 MPa under dry conditions. The composites comprising 5 wt % of G1 and G3 dendrimers, with ester bond densities of 0.208 and 0.297 mmol/g, respectively, reached a mass loss up to 0.27% in phosphate buffered saline at 37 degree celsius, which is within the range of established polycaprolactone (PCL). Combined with the nontoxic properties extracted from the cell viability study, polyester dendrimers were determined as promising additives which compatibilized well with the TATO formulation and cross-linked efficiently resulting in strong composites suited for bone fracture fixations.