Patrick Weber

Last Name

Weber

First Name

Patrick

ORCID

0000-0003-3626-000X

Organisational unit

03949 - Zenobi-Wong, Marcy / Zenobi-Wong, Marcy

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Publications 1 - 10 of 15

Synergizing Algorithmic Design, Photoclick Chemistry and Multi-Material Volumetric Printing for Accelerating Complex Shape Engineering
Chansoria, Parth; Rütsche, Dominic; Wang, Anny; et al. (2023)
Advanced Science
The field of biomedical design and manufacturing has been rapidly evolving, with implants and grafts featuring complex 3D design constraints and materials distributions. By combining a new coding-based design and modeling approach with high-throughput volumetric printing, a new approach is demonstrated to transform the way complex shapes are designed and fabricated for biomedical applications. Here, an algorithmic voxel-based approach is used that can rapidly generate a large design library of porous structures, auxetic meshes and cylinders, or perfusable constructs. By deploying finite cell modeling within the algorithmic design framework, large arrays of selected auxetic designs can be computationally modeled. Finally, the design schemes are used in conjunction with new approaches for multi-material volumetric printing based on thiol-ene photoclick chemistry to rapidly fabricate complex heterogeneous shapes. Collectively, the new design, modeling and fabrication techniques can be used toward a wide spectrum of products such as actuators, biomedical implants and grafts, or tissue and disease models.
Zwitterionic Polymers for the Diagnosis and Treatment of Osteoarthritis
Weber, Patrick (2024)
Ionically annealed zwitterionic microgels for bioprinting of cartilaginous constructs
Surman, František; Asadikorayem, Maryam; Weber, Patrick; et al. (2024)
Biofabrication
Foreign body response (FBR) is a pervasive problem for biomaterials used in tissue engineering. Zwitterionic hydrogels have emerged as an effective solution to this problem, due to their ultra-low fouling properties, which enable them to effectively inhibit FBR in vivo. However, no versatile zwitterionic bioink that allows for high resolution extrusion bioprinting of tissue implants has thus far been reported. In this work, we introduce a simple, novel method for producing zwitterionic microgel bioink, using alginate methacrylate (AlgMA) as crosslinker and mechanical fragmentation as a microgel fabrication method. Photocrosslinked hydrogels made of zwitterionic carboxybetaine acrylamide (CBAA) and sulfobetaine methacrylate (SBMA) are mechanically fragmented through meshes with aperture diameters of 50 and 90 mu m to produce microgel bioink. The bioinks made with both microgel sizes showed excellent rheological properties and were used for high-resolution printing of objects with overhanging features without requiring a support structure or support bath. The AlgMA crosslinker has a dual role, allowing for both primary photocrosslinking of the bulk hydrogel as well as secondary ionic crosslinking of produced microgels, to quickly stabilize the printed construct in a calcium bath and to produce a microporous scaffold. Scaffolds showed similar to 20% porosity, and they supported viability and chondrogenesis of encapsulated human primary chondrocytes. Finally, a meniscus model was bioprinted, to demonstrate the bioink's versatility at printing large, cell-laden constructs which are stable for further in vitro culture to promote cartilaginous tissue production. This easy and scalable strategy of producing zwitterionic microgel bioink for high resolution extrusion bioprinting allows for direct cell encapsulation in a microporous scaffold and has potential for in vivo biocompatibility due to the zwitterionic nature of the bioink.
Zwitterionic polymer-dexamethasone conjugates penetrate and protect cartilage from inflammation
Weber, Patrick; Asadikorayem, Maryam; Surman, František; et al. (2024)
Materials Today Bio
Improving the pharmacokinetics of intra-articularly injected therapeutics is a major challenge in treating joint disease. Small molecules and biologics are often cleared from the joint within hours, which greatly reduces their therapeutic efficacy. Furthermore, they are often injected at high doses, which can lead to local cytotoxicity and systemic side effects. In this study, we present modular polymer-drug conjugates of zwitterionic poly(carboxybetaine acrylamide) (pCBAA) and the anti-inflammatory glucocorticoid dexamethasone (DEX) to create cartilage-targeted carriers with slow-release kinetics. pCBAA polymers showed excellent cartilage penetration (full thickness in 1 h) and retention (>50 % after 2 weeks of washing). DEX was loaded onto the pCBAA polymer by employing two different DEX-bearing comonomers to produce pCBAA-co-DEX conjugates with different release kinetics. The slow-releasing conjugate showed zero-order release kinetics in PBS over 70 days. The conjugates elicited no oxidative stress on chondrocytes compared to dose-matched free DEX and protected bovine cartilage explants from the inflammatory response after treatment with IL-1β. By combining cartilage targeting and sustained drug release properties, the pCBAA-co-DEX conjugates solve many issues of today's intra-articular therapeutics, which could ultimately enable better long-term clinical outcomes with fewer side effects.
The collagenase-induced osteoarthritis (CIOA) model: Where mechanical damage meets inflammation
Weber, Patrick; Bevc, Kajetana; Fercher, David; et al. (2024)
Osteoarthritis and Cartilage Open
Objective: To characterize inflammatory and mechanical changes in the collagenase-induced OA (CIOA) model in rats. Design: Skeletally mature, 6-month-old Wistar rats received unilateral intraarticular injections of saline, 500 U or 1000 U of collagenase on days 0 and 2 of the study. Joint tissues were harvested on either day 4 or 70 to evaluate the acute and long-term changes. Blood biomarkers, gait asymmetry and mechanical hyperalgesia were assessed repeatedly up until day 70. Results: The intraarticular injection of collagenase triggered an increase in cartilage degeneration and bone resorption over time, particularly for 1000 U. Similarly, mild synovitis was observed on day 70 with an increased number of synovial lining cells, increased fibrosis, and infiltration of peripheral macrophages. Mechanistically, these findings were linked to a dose-related mechanical weakening of the anterior cruciate ligament (ACL), which caused persistent joint destabilization throughout the study. Furthermore, the collagenase injection triggered acute inflammation and swelling of the synovium on day 4 and an acute systemic inflammatory response with increased cytokine and peripheral blood immune cell levels. While mild synovitis persisted until day 70, the systemic inflammatory response returned to control levels after 8 days. Similarly, the observed acute changes in gait and mechanical hyperalgesia also returned to baseline after 21 days. Conclusion: By evaluating inflammatory and mechanical factors at different doses and timepoints, our characterization enables a more targeted study design and increases the clinical relevance of future studies involving the CIOA model.
Zwitterionic Granular Hydrogel for Cartilage Tissue Engineering
Asadikorayem, Maryam; Surman, František; Weber, Patrick; et al. (2023)
Advanced Healthcare Materials
Zwitterionic hydrogels have high potential for cartilage tissue engineering due to their ultra-hydrophilicity, nonimmunogenicity, and superior antifouling properties. However, their application in this field has been limited so far, due to the lack of injectable zwitterionic hydrogels that allow for encapsulation of cells in a biocompatible manner. Herein, a novel strategy is developed to engineer cartilage employing zwitterionic granular hydrogels that are injectable, self-healing, in situ crosslinkable and allow for direct encapsulation of cells with biocompatibility. The granular hydrogel is produced by mechanical fragmentation of bulk photocrosslinked hydrogels made of zwitterionic carboxybetaine acrylamide (CBAA), or a mixture of CBAA and zwitterionic sulfobetaine methacrylate (SBMA). The produced microgels are enzymatically crosslinkable using horseradish peroxidase, to quickly stabilize the construct, resulting in a microporous hydrogel. Encapsulated human primary chondrocytes are highly viable and able to proliferate, migrate, and produce cartilaginous extracellular matrix (ECM) in the zwitterionic granular hydrogel. It is also shown that by increasing hydrogel porosity and incorporation of SBMA, cell proliferation and ECM secretion are further improved. This strategy is a simple and scalable method, which has high potential for expanding the versatility and application of zwitterionic hydrogels for diverse tissue engineering applications.
In-situ-forming zwitterionic hydrogel does not ameliorate osteoarthritis in vivo, despite protective effects ex vivo
Asadikorayem, Maryam; Weber, Patrick; Zhang, Shipin; et al. (2025)
Biomaterials Advances
Osteoarthritis (OA) is one of the most common degenerative joint diseases, with no effective therapeutic options available. In this study, we aimed to develop an interpenetrating, in-situ-forming hydrogel based on biocompatible and anti-fouling zwitterionic (ZI) polymers for early-stage OA treatment. We hypothesized that the anti-fouling properties of zwitterions could provide tissue protection, and the high charge density of these polymers would enhance tissue penetration and lubrication. The hydrogel comprises carboxybetaine acrylamide as the ZI backbone and tyramine acrylamide as a functional comonomer to enable enzymatic and tissue-adhesive crosslinking. The hydrogel demonstrated exceptional tissue penetration and long-term retention in bovine cartilage explants. Moreover, hydrogel application protected cartilage in inflammatory media, enhanced lubrication, and decreased permeability. However, ZI hydrogel injection in collagenase-induced osteoarthritis model in rats did not prevent cartilage degeneration, and similar levels of tissue degradation and surface roughness were observed in rats injected with the ZI hydrogel and in OA controls. Additionally, ZI polymer without in-situ crosslinking resulted in increased cartilage degradation compared to both hydrogel and OA control. Furthermore, synovial tissue inflammation and significantly increased immune cell infiltration were observed in response to ZI materials. This study highlights the potential immunogenicity effect of ZI polymers in our disease model, contributing to impaired protective effects as well as exacerbated degeneration.
Filamented Light (FLight) Bioprinting of Mini-Muscles with Self-Renewal Potential
Liu, Hao; Winkelbauer, Michael; Janiak, Jakub; et al. (2025)
Advanced Materials
The plasticity and regenerative capacity of skeletal muscle arise from quiescent stem cells activated upon overload, injury, or disease state. Developing in vitro muscle models to study these properties can advance muscle disease modeling and pre-clinical evaluation. Here, Filamented Light (FLight) bioprinting is leveraged as a high-throughput approach for producing mini-muscle tissues. Using paired box protein 7 (Pax7)-nGFP primary myoblasts, mini-muscles are bioprinted from pristine collagen-fibrinogen (ColFib). The FLight hydrogel consist of aligned microstructures which guide the formation of aligned myotubes. Mini-muscles demonstrates in vivo-like tissue organization, including multinucleated myotubes and a Pax7⁺ cell pool embedded in newly deposited laminin. Both spontaneous and electrically stimulated contractions are observed. ColFib matrix is promising for maintenance of the Pax7⁺ cell pool. Damage from cardiotoxin-induced injury of the mini-muscles led to a massive proliferation of Pax7⁺ cells and restoration of the contractile properties of myotubes. Notably, small molecules such as Repsox can enhance regeneration. FLight printed mini-muscles have potential for applications in muscle biology, exercise/atrophy, disease models, and drug screening.
Zwitterionic poly-carboxybetaine-dexamethasone conjugates do not alleviate cartilage degeneration and synovitis in the collagenase-induced osteoarthritis model in rats
Weber, Patrick; Asadikorayem, Maryam; Zhang, Shipin; et al. (2025)
Scientific Reports
Osteoarthritis is a degenerative joint disease for which there is yet to be a disease-modifying drug available in clinics. New drug candidates often fail due to a combination of poor pharmacokinetics as well as an inability to address the complex, multifactorial nature of osteoarthritis. To address these issues, we developed a zwitterionic poly-carboxybetaine acrylamide-dexamethasone (pCBAA-DEX) conjugate showing good cartilage penetration as well as anti-inflammatory and lubricating properties in previous in vitro studies. Here, we investigate the therapeutic potential of pCBAA-DEX in the collagenase-induced osteoarthritis (CIOA) model in rats. Upon induction of the model, animals received one-time, unilateral injections of either saline, DEX or pCBAA-DEX on day 4 (N = 8). On day 70, joint tissues were harvested and analyzed. While pCBAA-DEX achieved ~ 50% cartilage retention at the terminal timepoint, it did not prevent cartilage degeneration, synovial inflammation and synovial fibrosis, nor did DEX alone. Nevertheless, DEX and pCBAA-DEX slightly decreased the fibrosis levels in the synovium with DEX also decreasing the number of synovial lining layers. For the cartilage, DEX did not cause any notable differences, instead we observed an increase in cartilage degeneration in the pCBAA-DEX group. These findings challenge the previous in vitro results and motivate a substantial redesign of these conjugates and associated in vitro methods to reconsider them for the treatment of osteoarthritis.
Zwitterionic Poly-Carboxybetaine Polymers Restore Lubrication of Inflamed Articular Cartilage
Weber, Patrick; Asadikorayem, Maryam; Zenobi-Wong, Marcy (2024)
Advanced Healthcare Materials
Osteoarthritis is a degenerative joint disease that is associated with decreased synovial fluid viscosity and increased cartilage friction. Though viscosupplements are available for decades, their clinical efficacy is limited and there is ample need for more effective joint lubricants. This study first evaluates the tribological and biochemical properties of bovine articular cartilage explants after stimulation with the inflammatory cytokine interleukin-1 beta. This model is then used to investigate the tribological potential of carboxybetaine (CBAA)-based zwitterionic polymers of linear and bottlebrush architecture. Due to their affinity for cartilage tissue, these polymers form a highly hydrated surface layer that decreases friction under high load in the boundary lubrication regime. For linear pCBAA, these benefits are retained over several weeks and the relaxation time of cartilage explants under compression is furthermore decreased, thereby potentially boosting the weeping lubrication mechanism. Bottlebrush bb-pCBAA shows smaller benefits under boundary lubrication but is more viscous than linear pCBAA, therefore providing better lubrication under low load in the fluid-film regime and enabling a longer residence time to bind to the cartilage surface. Showing how CBAA-based polymers restore the lost lubrication mechanisms during inflammation can inspire the next steps toward more effective joint lubricants in the future.

Publications 1 - 10 of 15

Patrick Weber

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