Maryam Asadikorayem

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Asadikorayem

First Name

Maryam

ORCID

0000-0002-3504-4543

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Publications1 - 10 of 13

Growth factor–loaded sulfated microislands in granular hydrogels promote hMSCs migration and chondrogenic differentiation
Puiggalí-Jou, Anna; Asadikorayem, Maryam; Maniura-Weber, Katharina; et al. (2023)
Acta Biomaterialia
Cell-based therapies for articular cartilage lesions are expensive and time-consuming; clearly, a one-step procedure to induce endogenous repair would have significant clinical benefits. Acellular heterogeneous granular hydrogels were explored for their injectability, cell-friendly cross-linking, and ability to promote migration, as well as to serve as a scaffold for depositing cartilage extracellular matrix. The hydrogels were prepared by mechanical sizing of bulk methacrylated hyaluronic acid (HAMA) and bulk HAMA incorporating sulfated HAMA (SHAMA). SHAMA's negative charges allowed for the retention of positively charged growth factors (GFs) (e.g., TGFB3 and PDGF-BB). Mixtures of HAMA and GF-loaded SHAMA microgels were annealed by enzymatic cross-linking, forming heterogeneous granular hydrogels with GF deposits. The addition of GF loaded sulfated microislands guided cell migration and enhanced chondrogenesis. Granular heterogeneous hydrogels showed increased matrix deposition and cartilage tissue maturation compared to bulk or homogeneous granular hydrogels. This advanced material provides an ideal 3D environment for guiding cell migration and differentiation into cartilage. Statement of significance: Acellular materials which promote regeneration are of great interest for repair of cartilage defects, and they are more cost- and time-effective compared to current cell-based therapies. Here we develop an injectable, granular hydrogel system which promotes cell migration from the surrounding tissue, facilitating endogenous repair. The hydrogel architecture and chemistry were optimized to increase cell migration and extracellular matrix deposition. The present study provides quantitative data on the effect of microgel size and chemical modification on cell migration, growth factor retention and tissue maturation.
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.
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.
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.
Development and Characterization of Zwitterionic Materials for Cartilage Tissue Engineering
Asadikorayem, Maryam (2024)
Tissue engineering is a multidisciplinary field that aims to restore and regenerate damaged tissues and organs by integrating principles from biology, materials science, and engineering, among others. Cartilage tissue, being one of the initial targets of tissue engineering, still requires optimal strategies to address various aspects and stages of its diseases. Currently available clinical interventions have proven suboptimal, leaving a large population in pain and with limited mobility. Moreover, due to the lack of regenerative capacity in cartilage, failure to treat injuries and diseases at earlier stages leads to degenerative conditions, ultimately requiring total knee replacement, which is a highly invasive treatment with many complications. Developing versatile biomaterials, as one of the critical pillars of tissue engineering, is a key research field that has stimulated a large body of ongoing research. The challenge lies in balancing optimal compatibility with enhanced functionality. This dissertation attempts to address this challenge in cartilage tissue engineering by developing biocompatible and versatile biomaterial platforms and conducting comprehensive in vitro and in vivo characterization. To achieve this, zwitterionic materials were chosen as the backbone for the developed biomaterials, based on extensive literature suggesting their exceptional in vivo compatibility, which stems from their unique chemical structure. Zwitterions possess equal amounts of cationic and anionic moieties, resulting in strong hydration. This hydration provides properties such as lubrication and antifouling, contributing to their in vivo compatibility. While they seem ideal candidates for cartilage tissue engineering, the range of zwitterionic-based biomaterials developed for this purpose remains limited and lacks versatility. This dissertation presents a series of studies on zwitterionic biomaterials with additional functional properties, making them suitable for cartilage tissue engineering and opening up new applications. To do this, two distinct biomaterial platforms were developed, each with unique characteristics and applications. The first biomaterial platform utilizes an emerging class of microporous scaffolds known as granular hydrogels, which possess multiple functional properties. In the first study, a novel class of zwitterionic granular hydrogels is introduced as an injectable formulation for cartilage tissue engineering, allowing for direct cell encapsulation and in vitro tissue maturation. In a separate study, the modularity of this platform is exploited to characterize and optimize scaffold biophysical properties, such as stiffness and porosity, to enhance chondrogenesis. Another study explores the use of zwitterionic granular hydrogels as (bio)inks for 3D extrusion bioprinting, enabling the fabrication of large cartilaginous constructs with overhang features at high resolution. The final study in this category includes in vitro and in vivo immune response characterization of these zwitterionic granular hydrogels, using subcutaneous implantation in mice and comparing them to hyaluronic acid granular hydrogels. The second biomaterial platform introduced in this dissertation is an injectable, in-situ-forming hydrogel based on zwitterions, designed to treat early-stage osteoarthritis by providing tissue protection and lubrication. Comprehensive ex vivo characterization is performed on cartilage explants to assess tissue penetration, retention, lubrication, and reinforcement effects. Additionally, in vivo performance is investigated using a collagenase-induced osteoarthritis model in rats. In the last chapter of this dissertation, a collaborative project is presented on an advanced casting technique for developing multilayered tissue transplants. While not based on zwitterions, this project employs the biomaterial strategies developed in this dissertation, enabling the use of eluting molds to fabricate multilayered, multicellular constructs with high resolution. Finally, the dissertation concludes with a summary of the major findings and key take-home messages from all the presented studies.
Modular iodinated carboxybetaine copolymers as charge-sensitive contrast agents for the detection of cartilage degradation
Weber, Patrick; Maier, Annalena; Fercher, David; et al. (2024)
Materials Today Bio
Accurately assessing cartilage tissue degradation is a big challenge in osteoarthritis (OA) research, as histology only provides information about a 2D tissue section, and currently available contrast agents for tomographic evaluation suffer from low specificity. In this study, we present a modular platform based on zwitterionic carboxybetaine (CBAA) to create multivalent polymeric contrast agents for x-ray computed tomography (CT) with high specificity towards the anionic glycosaminoglycans in the cartilage tissue. By copolymerizing CBAA with different ratios of anionic and cationic iodinated comonomers, we created a library of polymers with net charges ranging from strongly anionic to strongly cationic. The polymers were applied onto osteochondral plugs with different degradation states and the resulting CT images compared to histological stainings. In healthy tissues, the bulk contrast enhancement was strongly correlated with polymer charge, with cationic polymers reaching a 2-fold stronger contrast compared to established small molecule contrast agents. While a further increase in cationic charge slowed the penetration, it increased the polymer's specificity, thereby enabling the most cationic polymer C40 (40 mol% cationic iodinated comonomer) to discriminate accurately between tissues treated with IL-1β for 0, 1, 2 and 3 weeks. Moreover, this polymer also showed a strong local specificity, visualizing local differences in GAG distribution with significantly increased accuracy compared to the controls. Our polymer contrast agents show the importance of multivalency and charge control for the accurate, volumetric detection of GAGs in the cartilage tissue and paves the way towards new contrast agents in- and outside of the clinic.
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.
Porosity dominates over microgel stiffness for promoting chondrogenesis in zwitterionic granular hydrogels
Asadikorayem, Maryam; Brunel, Lucia G.; Weber, Patrick; et al. (2024)
Biomaterials Science
Granular hydrogels comprised of jammed, crosslinked microgels offer great potential as biomaterial scaffolds for cell-based therapies, including for cartilage tissue regeneration. As stiffness and porosity of hydrogels affect the phenotype of encapsulated cells and the extent of tissue regeneration, the design of tunable granular hydrogels to control and optimize these parameters is highly desirable. We hypothesized that chondrogenesis could be modulated using a granular hydrogel platform based on biocompatible, zwitterionic materials with independent intra- and inter-microgel crosslinking mechanisms. Microgels are made with mechanical fragmentation of photocrosslinked zwitterionic carboxybetaine acrylamide (CBAA) and sulfobetaine methacrylate (SBMA) hydrogels, and secondarily crosslinked in the presence of cells using horseradish peroxide (HRP) to produce cell-laden granular hydrogels. We varied the intra-microgel crosslinking density to produce microgels with varied stiffnesses (1-3 kPa) and swelling properties. These microgels, when resuspended at the same weight fraction and secondarily crosslinked, resulted in granular hydrogels with distinct porosities (5-40%) due to differing swelling properties. The greatest extent of chondrogenesis was achieved in scaffolds with the highest microgel stiffness and highest porosity. However, when scaffold porosity was kept constant and just microgel stiffness varied, cell phenotype and chondrogenesis were similar across scaffolds. These results indicate the dominant role of granular scaffold porosity on chondrogenesis, whereas microgel stiffness appears to play a relatively minor role. These observations are in contrast to cells encapsulated within conventional bulk hydrogels, where stiffness has been shown to significantly affect chondrocyte response. In summary, we introduce chemically-defined, zwitterionic biomaterials to fabricate versatile granular hydrogels allowing for tunable scaffold porosity and microgel stiffness to study and influence chondrogenesis.
Biofabrication of anisotropic articular cartilage based on decellularized extracellular matrix
Puiggalí-Jou, Anna; Hui, Isabel; Baldi, Lucrezia; et al. (2025)
Biofabrication
Tissue-engineered grafts that mimic articular cartilage show promise for treating cartilage injuries. However, engineering cartilage cell-based therapies to match zonal architecture and biochemical composition remains challenging. Decellularized articular cartilage extracellular matrix (dECM) has gained attention for its chondro-inductive properties, yet dECM-based bioinks have limitations in mechanical stability and printability. This study proposes a rapid light-based bioprinting method using a tyrosine-based crosslinking mechanism, which does not require chemical modifications of dECM and thereby preserves its structure and bioactivity. Combining this resin with Filamented Light (FLight) biofabrication enables the creation of cellular, porous, and anisotropic dECM scaffolds composed of aligned microfilaments. Specifically, we focus on the effects of various biopolymer compositions (i.e. hyaluronic acid, collagen I, and dECM) and inner architecture (i.e. bulk light vs FLight) on immune response and cell morphology, and we investigate their influence on nascent ECM production and long-term tissue maturation. Our findings highlight the importance of FLight scaffolds in directing collagen deposition resembling articular cartilage structure and promoting construct maturation, and they emphasize the superiority of biological-rich dECM over single-component materials for engineering articular cartilage, thereby offering new avenues for the development of effective cartilage tissue engineering strategies.
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.

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Maryam Asadikorayem

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