Bioactive Patient-Specific Implants for Regeneration of Critical Size Bone Defects

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School of Chemical Technology | Doctoral thesis (article-based) | Defence date: 2023-09-22
Degree programme
86 + app. 112
Aalto University publication series DOCTORAL THESES, 134/2023
Bone possesses the ability to spontaneously heal itself. Traumatic injury or tumor resection can lead to a bone defect, a lack of bone where it should normally exist. If the deficit is larger than a diagnostic limit, the defect is said to be of critical size, therefore requiring clinical intervention. In such cases autologous bone, or a bioactive synthetic ceramic resembling the mineral component of bone, is used to fill the defect. Additive manufacturing (AM) of bone tissue engineering scaffolds presents an adaptable method for fabrication of patient-specific implants for the same clinical reconstruction. In this thesis polymer/tricalcium phosphate (TCP) composites for bone regeneration scaffolds were studied with the ultimate goal of manufacturing large implants for craniomaxillofacial reconstruction. Such a materials should possess physico-chemical properties optimal for inducing bone growth while being suitable for AM. Within the work two very different methods of AM and therefore also two unique polymer groups were investigated. Poly(trimethylene carbonate) (PTMC) was synthetized for preparing resins for vat photopolymerization. PTMC/TCP composite scaffolds with varying ceramic ratio were characterized to evaluate their performance. The encouraging results showed that large amounts of a TCP could be incorporated into the scaffolds, therefore reinforcing the biocompatible scaffold and turning it bioactive. The AM method allows full control over scaffold design for optimal bone regeneration enabling fine pore architectures and a bioactive surface of TCP with a microscale topographical surface roughness. The process was subsequently upscaled and augmented for consistent manufacturing of large patient-specific implants. Following successful initial screening the composite scaffolds were tested in vivo in two animal models including cranial and tibia defect in rabbits and proof-of-concept pre-clinical study in the mandible of minipigs. Results in the small animal model showed promising results showing that scaffolds provide a conductive surface that induces bone formation. The minipig study confirmed these findings, but PTMC/TCP scaffolds were associated with elevated incidence of infection likely due to high local concentrations of TCP. Therefore, the results point out an intricate balance between biocompatibility and bioactivity. As an alternative method, well-established and commercially readily available medical grade poly(L-lactide-co-D,L-lactide) and poly(L-lactide-co-glycolide) were evaluated in composites with TCP for fused filament fabrication. Comparable scaffolds could successfully be manufactured and the general properties were promising. However, based on further evaluation of existing clinical data and considering the specific clinical application, some challenges remain and potential risks need to be recognized.
Supervising professor
Seppälä, Jukka, Prof., Aalto University, Department of Chemical and Metallurgical Engineering, Finland
Thesis advisor
Seppälä, Jukka, Prof., Aalto University, Department of Chemical and Metallurgical Engineering, Finland
van Bochove, Bas, Dr., University of Twente, Netherlands
Partanen, Jouni, Prof., Aalto University, Finland
patient-specific, bone regeneration, additive manufacturing, vat photopolymerization, fused filament fabrication, poly(trimethylene carbonate), aliphatic polyesters, tricalcium phosphate
Other note
  • [Publication 1]: Dienel Kasper, van Bochove Bas and Seppälä Jukka. 2019. Additive Manufacturing of Bioactive Poly(trimethylene carbonate)/β-Tricalcium Phosphate Composites for Bone Regeneration. Biomacromolecules, volume 21, issue 2, pages 366-376.
    Full text in Acris/Aaltodoc:
    DOI: 10.1021/acs.biomac.9b01272 View at publisher
  • [Publication 2]: Teotia Arun, Dienel Kasper, Qayoom Irfan, van Bochove Bas, Gupta Sneha, Partanen Jouni, Seppälä Jukka and Kumar Ashok. 2020. Improved Bone Regeneration in Rabbit Bone Defects Using 3D Printed Composite Scaffolds Functionalized with Osteoconductive Factors. ACS Applied Materials and Interfaces, volume 12, issue 43, pages 48340-48356.
    Full text in Acris/Aaltodoc:
    DOI: 10.1021/acsami.0c13851 View at publisher
  • [Publication 3]: Dienel Kasper, Abu-Shahba Ahmed, Kornilov Roman, Björkstrand Roy, van Bochove Bas, Snäll Johanna, Wilkman Tommy, Mesimäki Karri, Meller Anna, Lindén Jere, Lappalainen Anu, Partanen Jouni, Seppänen-Kaijansinkko Riitta, Seppälä Jukka and Mannerström Bettina. 2022. Patient-Specific Bioimplants and Reconstruction Plates for Mandibular Defects: Production Workflow and In Vivo Large Animal Model Study. Macromolecular Bioscience, volume 22, issue 4, 2100398.
    Full text in Acris/Aaltodoc:
    DOI: 10.1002/mabi.202100398 View at publisher
  • [Publication 4]: Dienel Kasper, van Bochove Bas, Lipponen Sami and Seppälä Jukka. 2023. Patient-Specific Bone Regeneration Implants Manufactured by Fused Filament Fabrication from Medical Grade Bioactive Composites. Under review in journal Materials Today Communications