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Development of advanced bioglass-polymer scaffolds for OSTEOCHONdral interface tissue regeneration

Periodic Reporting for period 1 - OSTEOCHON (Development of advanced bioglass-polymer scaffolds for OSTEOCHONdral interface tissue regeneration)

Reporting period: 2023-09-01 to 2025-08-31

Degenerative defects and injuries at the interface between cartilage and subchondral bone are difficult to treat because the two tissues differ strongly in structure, composition, vascularization and mechanical behavior. Current clinical options often address only one of the tissues, resulting in limited long-term regeneration and frequent re-interventions. At the same time, there is a clear European interest in advancing biomaterials and biofabrication technologies that can be standardized, better controlled, and ultimately translated into clinical use.

The OSTEOCHON project aimed to design and develop hybrid osteochondral scaffolds that combine mechanical strength with biological compatibility through the smart design of materials combining structure and function. The work progressed from individual material systems toward proof-of-concept hybrid constructs. The main applicable outcomes concern hydrogel formulations with tunable mechanical and biological properties, including RGD-functionalized and double-network systems, which showed promising potential for future biological evaluation. Optimization of bioactive-glass scaffolds and their integration into composite systems continues beyond the fellowship. Together, these results provide methodological and material foundations for further development of hybrid scaffolds for osteochondral tissue regeneration.
The research followed a logical progression from individual material components toward their integration into hybrid osteochondral constructs.

The first stage concentrated on developing bioactive-glass scaffolds with suitable composition and architecture for the bone side of the defect. Additive manufacturing (3D printing with a polymer carrier) and subsequent sintering (polymer debinding) were optimized to obtain structures with adequate mechanical integrity and open porosity, providing robust supports for later combination with soft hydrogel materials. Further optimization of the sintering process is continuing beyond the project period.

In parallel, the project explored soft hydrogel systems designed for biological interaction. The initially proposed gellan-gum cryogels could not be realized under the tested conditions, as premature gelation during cooling prevented proper ice-templating and pore formation. Work therefore focused on alternative poly(amino-acid)- and poly(2-oxazoline)-based systems. Modification of the poly(2-oxazoline) network with short RGD peptides through thiol-ene chemistry offered a bioactive interface capable of stimulating cell adhesion without relying on added growth factors. Additionally, the project contributed to understanding hydrogel reinforcement through the introduction of a second network to form double-network structures, which opened a new research direction.

Preliminary composite scaffolds were fabricated only as proof of concept. These were produced using non-bioactive-glass supports and simple monomeric mixtures, since the optimization of the bioactive-glass sintering was still in progress and the available scaffolds were not yet suitable for reliable hydrogel infiltration or biological testing. This preliminary work made it possible to assess the basic feasibility of combining soft and rigid phases, confirming that the chosen strategy allows good interfacial integration and providing a practical route toward hybrid osteochondral constructs to be further developed after the project.

A one-month secondment at the Institute of Physiology of the Czech Academy of Sciences focused on biological evaluation and cell-culture experiments with the hydrogel systems. This stay provided practical training in cell-culture and biological-assessment methods, broadening interdisciplinary competence and strengthening collaboration for continued studies beyond the fellowship.

Beyond research, the fellowship strengthened experimental and supervisory skills and established a new research direction at the host institution. The fellow’s appointment as Assistant Professor at UCT Prague ensures the continuation of this research line and its transfer to student projects and new collaborations.

Dissemination and communication activities included the presentation of results at international conferences and workshops, such as the Gel Symposium 2024 and ACS Fall Meeting 2025, as well as other invited talks. Additional dissemination took place through informal seminars and local presentations to colleagues and students. Public engagement was achieved through Researchers’ Night events, lectures, and the creation of outreach materials such as a scientific comic and coloring book. Manuscripts on hydrogel and double-network systems are in preparation, and the methodological outcomes are being further developed through ongoing research at the host institution and newly established collaborations.
The main applicable outcomes of the project concern the development of new hydrogel systems, while the work on bioactive-glass and combined scaffolds remains in progress.

The fellowship established new synthetic routes for poly(amino-acid)- and poly(2-oxazoline)-based hydrogels and cryogels, focusing on their structure-property relationships and biofunctionalization. Peptide modification of the poly(2-oxazoline) network through thiol-ene chemistry produced materials with tunable properties and cell-adhesive surfaces, offering a versatile platform for future biological studies. These systems expand the toolbox of photo-processable and biocompatible hydrogels and represent a step forward in the design of soft hydrogel materials for tissue engineering. In addition, work on double-network hydrogels provides valuable insight into the synergy mechanisms responsible for hydrogel toughening and will guide future development and assist other researchers in tailoring the mechanical properties of such materials for specific applications.
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