Jos Malda

• Utrecht University

Despite the growing prevalence of cartilage damage in the knee joint, effective regenerative treatments remain limited. One of the current challenges is the accurate matching of the local mechanical properties of the tissue, which vary throughout the articular joint surface. This study investigates the fabrication of cartilage constructs with aniso...

Articular cartilage can withstand substantial compressive and shear forces within the joint and also reduces friction during motion. The exceptional mechanical properties of articular cartilage stem from its highly organized extracellular matrix (ECM). The ECM is composed mainly of collagen type II and is pivotal in conferring mechanical durability...

Volumetric Bioprinting (VBP), enables to rapidly build complex, cell‐laden hydrogel constructs for tissue engineering and regenerative medicine. Light‐based tomographic manufacturing enables spatial‐selective polymerization of a bioresin, resulting in higher throughput and resolution than what is achieved using traditional techniques. However, meth...

Advances in tissue engineering are focused on devising improved therapeutics to reconstruct craniofacial bones. In cell-based strategies, biomaterials with specific physicochemical properties can mimic natural environments, supporting stem cell renewal, survivability, and cell fate. This study highlights the engineering of a 3D-printed (Melt Electr...

There is an increasing need for novel biomaterials compatible with advanced biofabrication technologies, which also permit cells to remodel their microenvironment. This remodelling is crucial for maturing tissue constructs into fully functional tissue replacements. Recent progress in supramolecular chemistries has allowed for the production of dyna...

We introduce Generative, Adaptive, Context-Aware 3D Printing (GRACE), a novel approach combining 3D imaging, computer vision, and parametric modelling to create tailored, context-aware geometries using volumetric additive manufacturing. GRACE rapidly and automatically generates complex structures capable of conforming directly around features rangi...

A novel approach merging melt electrowriting (MEW) with matched die thermoforming to achieve scaffolds with micron‐sized curvatures (200 – 800 µm versus 1000 µm of mandrel printing) for in vitro modeling of the kidney proximal tubule (PT) is proposed. Recent advances in this field emphasize the relevance of accurately replicating the intricate tiss...

Conventional static culture of organoids necessitates weekly manual passaging and results in nonhomogeneous exposure of organoids to nutrients, oxygen, and toxic metabolites. Here, we developed a miniaturized spinning bioreactor, RPMotion, specifically optimized for accelerated and cost-effective culture of epithelial organoids under homogeneous co...

The reconstruction of craniomaxillofacial bone defects remains clinically challenging. To date, autogenous grafts are considered the gold standard but present critical drawbacks. These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques....

The effective replication of microtubular structures in tissue engineering remains a great challenge. In this study, the temperature‐responsive characteristics of poly(N‐isopropylacrylamide) (pNIPAM) to create intricate, high‐resolution tubular structures through a shrinking mechanism is investigated by exploring 2 thermosensitive hydrogels–gelatin...

Volumetric Bioprinting (VBP), enables to rapidly build complex, cell-laden hydrogel constructs for tissue engineering and regenerative medicine. Light-based tomographic manufacturing enables spatial-selective polymerization of a bioresin, resulting in higher throughput and resolution than what achieved using traditional techniques. However, methods...

Despite extensive research, current methods for creating three-dimensional (3D) silk fibroin (SF) scaffolds lack control over molecular rearrangement, particularly in the formation of β-sheet nanocrystals that severely embrittle SF, as...

This study is the first to preserve cardiac tissue engineered constructs with encapsulated iPSC-derived cardiomyocytes under hypothermic- and cryogenic conditions.

Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, “Biology in Space and Analogue Environments”, focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present o...

Gingival recession, a prevalent condition affecting the gum tissues, is characterized by the exposure of tooth root surfaces due to the displacement of the gingival margin. This review explores conventional treatments, highlighting their limitations and the quest for innovative alternatives. Importantly, it emphasizes the critical considerations in...

Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without grav...

Hydrogels are ideal materials to encapsulate cells, making them suitable for applications in tissue engineering and regenerative medicine. However, they generally do not possess adequate mechanical strength to functionally replace human tissues, and therefore they often need to be combined with reinforcing structures. While the interaction at the i...

During evolution, animals have returned from land to water, adapting with morphological modifications to life in an aquatic environment. We compared the osteochondral units of the humeral head of marine and terrestrial mammals across species spanning a wide range of body weights, focusing on microstructural organization and biomechanical performanc...

This work reports the rational design and fabrication of magneto‐active microfiber meshes with controlled hexagonal microstructures via melt electrowriting (MEW) of a magnetized polycaprolactone‐based composite. In situ iron oxide nanoparticle deposition on oxidized graphene yields homogeneously dispersed magnetic particles with sizes above 0.5 µm...

Non-destructive assessments are required for the quality control of tissue-engineered constructs and the optimization of the tissue culture process. Near-infrared (NIR) spectroscopy coupled with machine learning (ML) provides a promising approach for such assessment. However, due to its nonspecific nature, each spectrum incorporates information on...

The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: “How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?” This is one of the five major scientific issues of the ESA road...

In articular cartilage (AC), the collagen arcades provide the tissue with its extraordinary mechanical properties. As these structures cannot be restored once damaged, functional restoration of AC defects remains a major challenge. We report that the use of a converged bioprinted, osteochondral implant, based on a gelatin methacryloyl cartilage pha...

Introduction: Advances in material science and cell technology offer new possibilities in myocardial repair. We test the safety and feasibility of implanting epicardial cellularized patches in a porcine ischemic cardiomyopathy model, representative of human disease. Methods: In pigs (n=4) , 90 min occlusion of the circumflex artery induced myocardi...

In living tissues, cells express their functions following complex signals from their surrounding microenvironment. Capturing both hierarchical architectures at the micro- and macroscale, and anisotropic cell patterning remains a major challenge in bioprinting, and a bottleneck towards creating physiologically-relevant models. Addressing this limit...

Pathological angiogenesis is a crucial attribute of several chronic diseases such as cancer, age-related macular degeneration, and osteoarthritis (OA). In the case of OA, pathological angiogenesis mediated by the vascular endothelial growth factor (VEGF), among other factors, contributes to cartilage degeneration and to implants rejection. In line...

Background: The use of acellular hydrogels to repair osteochondral defects requires cells to first invade the biomaterial and then to deposit extracellular matrix for tissue regeneration. Due to the diverse physicochemical properties of engineered hydrogels, the specific properties that allow or even improve the behaviour of cells are not yet clea...

To progress cardiac tissue engineering strategies closer to the clinic, thicker constructs are required to meet the functional need following a cardiac event. Consequently, pre-vascularization of these constructs needs to be investigated to ensure survival and optimal performance of implantable engineered heart tissue. The aim of this research is t...

Major advances in the field of periodontal tissue engineering have favored the fabrication of biodegradable membranes with tunable physical and biological properties for guided bone regeneration (GBR). Herein, we engineered innovative nanoscale beta-tricalcium phosphate (β-TCP)-laden gelatin methacryloyl/polycaprolactone (GelMA/PCL-TCP) photocrossl...

3D bioprinting has developed tremendously in the last couple of years and enables the fabrication of simple, as well as complex, tissue models. The international space agencies have recognized the unique opportunities of these technologies for manufacturing cell and tissue models for basic research in space, in particular for investigating the effe...

Major challenges in biofabrication revolve around capturing the complex, hierarchical composition of native tissues. However, individual 3D printing techniques have limited capacity to produce composite biomaterials with multi-scale resolution. Volumetric bioprinting recently emerged as a paradigm-shift in biofabrication. This ultra-fast, light-bas...

The surgical repair of articular cartilage remains an ongoing challenge in orthopedics. Tissue engineering is a promising approach to treat cartilage defects; however, scaffolds must (i) possess the requisite material properties to support neocartilage formation, (ii) exhibit sufficient mechanical integrity for handling during implantation, and (ii...

Despite extensive research, current methods for creating three-dimensional (3D) silk fibroin (SF) scaffolds lack control over molecular rearrangement, particularly in the formation of β-sheet nanocrystals, as well as hierarchical fiber organization at both micro- and macroscale. In this study, we introduce a fabrication process based on electrowrit...

Conventional additive manufacturing and biofabrication techniques are unable to edit the chemicophysical properties of the printed object postprinting. Herein, a new approach is presented, leveraging light‐based volumetric printing as a tool to spatially pattern any biomolecule of interest in custom‐designed geometries even across large, centimeter...

In living tissues, cells express their functions following complex signals from their surrounding microenvironment. Capturing both hierarchical architectures at the micro- and macroscale, and anisotropic cell patterning remains a major challenge in bioprinting, and therefore a bottleneck towards creating physiologically relevant models. Addressing...

Fluid pressure develops transiently within mechanically-loaded, cell-embedding hydrogels, but its magnitude depends on the intrinsic material properties of the hydrogel and cannot be easily altered. The recently developed melt-electrowriting (MEW) technique enables three-dimensional printing of structured fibrous mesh with small fibre diameter (20...

Purpose: Various sustained-release formulations incorporate high bupivacaine concentrations but data on local toxicity is lacking. This study explores local toxic effects of highly concentrated (5%) bupivacaine compared to clinically used concentrations in vivo following skeletal surgery, to assess the safety of sustained-release formulations with...

Periodontitis is a ubiquitous chronic inflammatory, bacteria-triggered oral disease affecting the adult population. If left untreated, periodontitis can lead to severe tissue destruction, eventually resulting in tooth loss. Despite previous efforts in clinically managing the disease, therapeutic strategies are still lacking. Herein, melt electrowri...

Bioprinting In article number 2210521, Khoon S. Lim, and co‐workers highlight a scaffolding approach to engineering blood vessels, starting from lego like construction of macro‐scale vessels to functional micro‐scale vessels. Programmable sacrificial bioinks are developed, and applied to a range of biofabrication platforms, introducing architectura...

Major challenges in biofabrication revolve around capturing the complex, hierarchical composition of native tissues. However, individual 3D printing techniques have limited capacity to produce composite biomaterials with multi-scale resolution. Volumetric bioprinting recently emerged as a paradigm-shift in biofabrication. This ultra-fast, light-bas...

Tunable culture platforms that guide cellular organization and mechanically stimulate skeletal muscle development are still unavailable due to limitations in biocompatibility and actuation triggered without contact. This study reports the rational design and fabrication of magneto-active microfiber meshes with controlled hexagonal microstructures v...

Sacrificial printing allows introduction of architectural cues within engineered tissue constructs. This strategy adopts the use of a 3D‐printed sacrificial ink that is embedded within a bulk hydrogel which is subsequently dissolved to leave open‐channels. However, current conventional sacrificial inks do not recapitulate the dynamic nature of tiss...

Periodontitis is a chronic inflammatory condition that often causes serious damage to tooth-supporting tissues. The limited successful outcomes of clinically available approaches underscore the need for therapeutics that cannot only provide structural guidance to cells but can also modulate the local immune response. Here, three-dimensional melt el...

Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, e...

Current biomaterial‐based strategies explored to treat articular cartilage defects have failed to provide adequate physico‐chemical cues in order to guide functional tissue regeneration. Here, it is hypothesized that atmospheric‐pressure plasma (APPJ) treatment and melt electrowriting (MEW) will produce microfiber support structures with covalently...

Remaining challenges in auricular cartilage tissue engineering include acquiring sufficient amounts of regeneration-competent cells and subsequent production of high quality neocartilage. Progenitor cells are a resident subpopulation of native cartilage, displaying a high proliferative and cartilage-forming capacity, yet their potential for regener...

The development of tissue engineering strategies for the treatment of large bone defects has become increasingly relevant, given the growing demand for bone substitutes. Native bone is composed of a dense vascular network necessary for the regulation of bone development, regeneration and homeostasis. A major obstacle in fabricating living, clinical...

During evolution, animals have returned from land to water, adapting with morphological modifications to life in an aquatic environment. We compared the osteochondral units of the humeral head of marine and terrestrial mammals across species spanning a wide range of body weights, focusing on microstructural organization and biomechanical performanc...

Adequate treatment of pain arising from spinal surgery is a major clinical challenge. Opioids are the mainstay of current treatment methods, but the frequency and severity of their side effects display a clear need for opioid-free analgesia. Local anesthetics have been encapsulated into sustained-release drug delivery systems to provide postoperati...

Microvasculature is essential for the exchange of gas and nutrient for most tissues in our body. Some tissue structures such as the meniscus presents spatially confined blood vessels adjacent to non-vascularized regions. In biofabrication, mimicking the spatial distribution of such vascular components is paramount, as capillary ingrowth into non-va...

Volumetric Bioprinting Volumetric bioprinting shapes organoid‐laden constructs into centimeter‐scale assemblies that mimic native liver function. In article number 2110054, Riccardo Levato and co‐workers report the development of a hydrogel‐based bioresin with tunable optical properties to minimize scattering in light‐based printing and ensure high...

Organ‐ and tissue‐level biological functions are intimately linked to microscale cell‐cell interactions and to the overarching tissue architecture. Together, biofabrication and organoid technologies offer the unique potential to engineer multi‐scale living constructs, with cellular microenvironments formed by stem cell self‐assembled structures emb...

Viscoelastic hydrogels are gaining interest as they possess necessary requirements for bioprinting and injectability. By means of reversible, dynamic covalent bonds, it is possible to achieve features that recapitulate the dynamic character of the extracellular matrix. Dually cross-linked and double-network (DN) hydrogels seem to be ideal for the d...

For nearly three decades, tissue engineering strategies have been leveraged to devise effective therapeutics for dental, oral, and craniofacial (DOC) regenerative medicine and treat permanent deformities caused by many debilitating health conditions. In this regard, additive manufacturing (AM) allows the fabrication of personalized scaffolds that h...

Hydrogels are of interest in cartilage tissue engineering due to their ability to support the encapsulation and chondrogenesis of mesenchymal stromal cells (MSCs). However, features such as hydrogel crosslink density, which can influence nutrient transport, nascent matrix distribution, and the stability of constructs during and after implantation m...

Three-dimensional (3D) bioprinting strategies use computer-aided processes to enable automated simultaneous spatial patterning of cells and/or biomaterials. These technologies are suitable for a broad range of biomedical applications owing to their capability to produce structurally sophisticated and functionally relevant tissue constructs. Extrusi...

Meniscus injury and meniscectomy are strongly related to osteoarthritis, thus there is a clinical need for meniscus replacement. The purpose of this study is to create a meniscus scaffold with micro-scale circumferential and radial fibres suitable for a one-stage cell-based treatment. Poly-caprolactone-based scaffolds with three different architect...

There is a need for long‐lived hepatic in vitro models to better predict drug induced liver injury (DILI). Human liver‐derived epithelial organoids are a promising cell source for advanced in vitro models. Here, organoid technology is combined with biofabrication techniques, which holds great potential for the design of in vitro models with complex...

Osteoarthritis of the hip is a painful and debilitating condition commonly occurring in humans and dogs. One of the main causes that leads to hip osteoarthritis is hip dysplasia. Although the current surgical methods to correct dysplasia work satisfactorily in many circumstances, these are associated with serious complications, tissue resorption, a...

Biofabrication exploits additive manufacturing techniques for creating 3D structures with a precise geometry that aim to mimic a physiological cellular environment and to develop the growth of native tissues. The most recent approaches of 3D biofabrication integrate multiple technologies into a single biofabrication platform combining different mat...

The recent societal debate on opioid use in treating postoperative pain has sparked the development of long-acting, opioid-free analgesic alternatives, often using the amino-amide local anesthetic bupivacaine as active pharmaceutical ingredient. A potential application is musculoskeletal surgeries, as these interventions rank amongst the most painf...

Periodontitis is a chronic inflammatory, bacteria‐triggered disorder affecting nearly half of American adults. Although some level of tissue regeneration is realized, its low success in complex cases demands superior strategies to amplify regenerative capacity. Herein, highly ordered scaffolds are engineered via Melt ElectroWriting (MEW), and the e...

From a materials perspective, the pillars for the development of clinically translatable scaffold-based strategies for craniomaxillofacial (CMF) bone and periodontal regeneration have included electrospinning and 3D printing (biofabrication) technologies. Here, we offer a detailed analysis of the latest innovations in 3D (bio)printing strategies fo...

To prevent the progression of posttraumatic osteoarthritis, assessment of cartilage composition is critical for effective treatment planning. Posttraumatic changes include proteoglycan (PG) loss and elevated water content. Quantitative dual‐energy computed tomography (QDECT) provides a means to diagnose these changes. Here, we determine the potenti...

Recent insights suggest that the osteochondral interface plays a central role in maintaining healthy articulating joints. Uncovering the underlying transport mechanisms is key to the understanding of the cross-talk between articular cartilage and subchondral bone. Here, we describe the mechanisms that facilitate transport at the osteochondral inter...

Bioengineering of the human auricle remains a significant challenge, where the complex and unique shape, the generation of high-quality neocartilage, and shape preservation are key factors. Future Regenerative Medicine (RM)-based approaches for auricular cartilage reconstruction will benefit from a smart combination of various strategies. Our appro...

Introduction: To date, tubular tissue engineering relies on large, non-porous tubular scaffolds (Ø > 2 mm) for mechanical self-support, or smaller (Ø 150–500 μm) tubes within bulk hydrogels for studying renal transport phenomena. To advance the engineering of kidney tubules for future implantation, constructs should be both self-supportive and yet...

Bioprinting has become an important tool for fabricating regenerative implants and in vitro cell culture platforms. However, until today, extrusion-based bioprinting processes are limited to resolutions of hundreds of micrometers, which hamper the reproduction of intrinsic functions and morphologies of living tissues. This study describes novel hyd...

Gelatine methacryloyl (GelMA) hydrogels are widely used in studies aimed at cartilage regeneration. However, the endotoxin content of commercially available GelMAs and gelatines used in these studies is often overlooked, even though endotoxins may influence several cellular functions. Moreover, regulations for clinical use of biomaterials dictate a...

Bioactive hydrogels based on naturally-derived polymers are of great interest for regenerative medicine applications. Among naturally-derived polymers, silk fibroin has been extensively explored as a biomaterial for tissue engineering due to its unique mechanical properties. Here, we demonstrate the rapid gelation of cell-laden silk fibroin hydroge...

Magnesium (Mg)-based alloys are promising biodegradable materials for bone repair applications. However, due to their rapid degradation and high corrosion rate, Mg-based alloys are typically associated with in vivo infections and implant failure. This study evaluated the synergistic stability and anti-inflammatory properties that could potentially...

Identification of articular cartilage progenitor cells (ACPCs) has opened up new opportunities for cartilage repair. These cells may be used as alternatives for or in combination with mesenchymal stromal cells (MSCs) in cartilage engineering. However, their potential needs to be further investigated, since only a few studies have compared ACPCs and...

Objective The aims of the study were to assess the anti-inflammatory properties of platelet-rich plasma (PRP) and investigate its regenerative potential in osteoarthritic (OA) human chondrocytes. We hypothesized that PRP can modulate the inflammatory response and stimulate cartilage regeneration. Design Primary human chondrocytes from OA knees wer...