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Enhanced Degradability of Thiol–Ene Composites through the Inclusion of Isosorbide-Based Polycarbonates
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.ORCID iD: 0000-0002-6501-6359
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.ORCID iD: 0000-0001-9946-8073
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.ORCID iD: 0000-0003-0028-1204
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.ORCID iD: 0000-0002-9200-8004
2024 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 16, no 30, p. 40056-40068Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Chemical Society (ACS) , 2024. Vol. 16, no 30, p. 40056-40068
Keywords [en]
composites, thiol−ene click chemistry, polycarbonates, degradability, bone fixation
National Category
Polymer Chemistry
Research subject
Chemistry; Fibre and Polymer Science; Materials Science and Engineering
Identifiers
URN: urn:nbn:se:kth:diva-361257DOI: 10.1021/acsami.4c09626ISI: 001273625800001PubMedID: 39031473Scopus ID: 2-s2.0-85199082008OAI: oai:DiVA.org:kth-361257DiVA, id: diva2:1944677
Projects
BoneFix
Funder
Knut and Alice Wallenberg Foundation, 2017.0300EU, Horizon 2020, 952150
Note

QC 20250317

Available from: 2025-03-14 Created: 2025-03-14 Last updated: 2025-03-18Bibliographically approved
In thesis
1. Redefining Bone Fracture Treatments: Injectable TATO Composites as degradable implantable fixators
Open this publication in new window or tab >>Redefining Bone Fracture Treatments: Injectable TATO Composites as degradable implantable fixators
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Abstract [sv]

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.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2025. p. 95
Series
TRITA-CBH-FOU ; 2025:7
National Category
Composite Science and Engineering Biomaterials Science Polymer Chemistry
Research subject
Fibre and Polymer Science
Identifiers
urn:nbn:se:kth:diva-361416 (URN)978-91-8106-233-5 (ISBN)
Public defence
2025-04-11, Kollegiesallen, Brinellvägen 6, https://kth-se.zoom.us/j/67806299673, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
EU, Horizon 2020, 952150
Note

QC 20250321

Embargo till och med 2026-04-11 godkänt av skolchef Amelie Eriksson Karlström via e-post 2025-03-21

Available from: 2025-03-21 Created: 2025-03-18 Last updated: 2025-03-24Bibliographically approved

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San Jacinto García, JorgeSanz del Olmo, NataliaHutchinson, DanielMalkoch, Michael

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