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Redefining Bone Fracture Treatments: Injectable TATO Composites as degradable implantable fixators
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.ORCID iD: 0000-0002-6501-6359
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Sustainable development
SDG 3: Good Health and Well-Being, SDG 9: Industry, innovation and infrastructure, SDG 12: Responsible consumption and production
Abstract [en]

Metal plates and screws have been used as the gold standard for Open Reduction Internal Fixation (ORIF) treatments of complex bone fractures for decades. However, the drawbacks of these implants necessitate a transition towards more patient-personalized treatments. Injectable adhesive composites that can cure rapidly on demand via photopolymerization have shown great potential in tissue repair surgeries. Such systems allow for a high level of in situ customization,which replaces the current need for surgeons to stockpile large quantities of different 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 were chosen to form crosslinked networks in conjunction with hydroxyapatite (HA). Degradability was introduced into the composite in two different ways. In the first approach, isosorbide-based polycarbonates in different weight percentages were included in the composite formulation, resulting in improved degradation rates while surpassing the mechanical properties needed for hand rehabilitation exercises. In the second approach, the introduction of ester moieties was combined with the partial replacement of HA with the more resorbable inorganic fillers tricalcium phosphate and bioactive glass. This led to a family of composites with a wide range of degradability profiles and mechanical properties, highlighting the tunability of these materials.

Inspired by dental composites, TATO-based primers containing allylfunctionalized monomers with either n-hydroxysuccinimide (NHS) or phosphonic acid (Phn) groups were developed. These monomers allowed for enhanced adhesion to bone and photopolymerization via TEC with the TATObased composite, resulting in an adhesive composite patch system capable of fixating bone fractures without the use of metal screws. The incorporation of these monomers allowed the primers to interact with collagen or hydroxyapatite present in the bone surface, resulting in shear strengths on bone substrates that outperformed existing commercially available superglues. These results demonstrate how acrylate-free primers and composites can be used in biocompatible, strong and biodegradable fixation patches, suitable for fracture fixation in non- or low-load bearing bones.

Abstract [sv]

Metallplattor och skruvar har i årtionden varit guldstandarden för öppen reposition 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. Injicerbara viskösa kemiska blandningar som kan härda med hjälp av fotokemi till starka kompositer för frakturbehandling har visat stor potential i laboratoriemiljö. Mer specifikt har styva och starka kompositbaserade implantat, baserade påtriazinetrion (TATO)-monomerer i kombination med hydroxiapatit (HA),uppvisat stor potential. Dessa system bildar tvärbundna nätverk genom ljushärdande tiol-en-kopplingskemi (TEC) vilket möjliggör fullständig polymerisation av monomerblandningar till kompositer. Kombinationen av icke-toxiska kompositer och mild kemi vid tillverkningen möjliggör en hög grad av patientanpassning, vilket i framtiden kan eliminera behovet av att sjukhusen upprätthåller stora lager av metallimplantat.

Tidigare studier har visat att TATO-kompositer är icke-nedbrytbara i prekliniska tester. Kirurgernas förväntningar på framtida implantat är dock starkt kopplade till nedbrytbara material. För att möta dessa behov utvecklades två olika materialsystem där nedbrytbarhet integrerades. I det första systemet inkluderades nedbrytbara polykarbonater baserade på isosorbid. utvecklades två olika materialsystem där nedbrytbarhet integrerades, samtidigt som de mekaniska egenskaperna överträffade de krav som ställs för rehabiliteringsövningar, exempelvis vid fingerfrakturer. I det andra systemet utvecklades nya TATO-monomerer med hydrolytiskt känsliga esterbindningar i kombination med resorberbara fyllmedel såsom trikalciumfosfat och bioaktivt glas. Detta resulterade i en ny familj av kompositer med en bred variation av nedbrytbarhetsprofiler och mekaniska egenskaper.

För att möjliggöra en fullständig ersättning av metallimplantat med adhesiva kompositer utvecklades även nya primersystem som effektivt kan förankra kompositer till blött ben. Inspirerade av dentala primersystem utvecklades nya TATO-baserade primrar, innehållande allylfunktionaliserade monomerer med antingen n-hydroxysuccinimid (NHS)- eller fosfonsyra (Phn)-grupper. Dessa system förbättrade vidhäftningen till ben och möjliggjorde fotopolymerisation via TEC med den TATO-baserade kompositen. De aktiva monomererna i primersystemen interagerade med kollagen och hydroxiapatit – de huvudsakliga komponenterna i ben – vilket resulterade i stark adhesion av kompositerna till bensubstrat, med skjuvhållfastheter som överträffade befintliga kommersiellt tillgängliga superlim. Slutligen utvärderades dessa system som adhesiva benplåster för att fixera benfrakturer utan behov av metallskruvar. Resultaten visar att akrylatfria primers och kompositer kan användas 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: urn:nbn:se:kth:diva-361416ISBN: 978-91-8106-233-5 (print)OAI: oai:DiVA.org:kth-361416DiVA, id: diva2:1945552
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

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

QC 20250321

Available from: 2025-03-21 Created: 2025-03-18 Last updated: 2026-04-11Bibliographically approved
List of papers
1. Enhanced Degradability of Thiol–Ene Composites through the Inclusion of Isosorbide-Based Polycarbonates
Open this publication in new window or tab >>Enhanced Degradability of Thiol–Ene Composites through the Inclusion of Isosorbide-Based Polycarbonates
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
Keywords
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:nbn:se:kth:diva-361257 (URN)10.1021/acsami.4c09626 (DOI)001273625800001 ()39031473 (PubMedID)2-s2.0-85199082008 (Scopus ID)
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
2. Photo-Curable Triazinetrione Composites with Tunable Degradation for Fracture Stabilization and Flexible Thin-Film Applications.
Open this publication in new window or tab >>Photo-Curable Triazinetrione Composites with Tunable Degradation for Fracture Stabilization and Flexible Thin-Film Applications.
(English)Manuscript (preprint) (Other academic)
Keywords
composites, bioresorbable fillers, thiol-ene chemistry, degradability, bone fixation, flexibility.
National Category
Materials Engineering
Identifiers
urn:nbn:se:kth:diva-361258 (URN)
Note

QC 20250317

Available from: 2025-03-14 Created: 2025-03-14 Last updated: 2025-03-18Bibliographically approved
3. Phosphonic Self-Etching Primers for Enhanced Bone Adhesion: Transition from Dentistry to Bone Fracture Fixation
Open this publication in new window or tab >>Phosphonic Self-Etching Primers for Enhanced Bone Adhesion: Transition from Dentistry to Bone Fracture Fixation
(English)Manuscript (preprint) (Other academic)
Keywords
thiol-ene chemistry, fracture fixation, screwless, enhanced adhesion, high performance, long-term stability, next-gen bone adhesives.
National Category
Biomaterials Science
Identifiers
urn:nbn:se:kth:diva-361259 (URN)
Note

QC 20250317

Available from: 2025-03-14 Created: 2025-03-14 Last updated: 2025-03-18Bibliographically approved
4. NHS-Functionalized Adhesive Primers: First Steps to New Standard-of-Care in Fracture Fixation
Open this publication in new window or tab >>NHS-Functionalized Adhesive Primers: First Steps to New Standard-of-Care in Fracture Fixation
(English)Manuscript (preprint) (Other academic)
National Category
Biomaterials Science
Identifiers
urn:nbn:se:kth:diva-361260 (URN)
Note

QC 20250317

Available from: 2025-03-14 Created: 2025-03-14 Last updated: 2025-03-18Bibliographically approved

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San Jacinto García, Jorge

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