Heinz Redl

• PhD
• PostDoc Position at Ludwig Boltzmann Institute Traumatology

Background Diagnosis of sepsis at the ICU admission is burdened by uncertainty. There is a need for an accurate identification of patients with sepsis from those with non-infectious, e.g. post-surgical and random trauma. We tested diagnostic utility of a novel biomarker, nucleoside t ⁶ A ( N ⁶ -threonylcarbamoyladenosine) in animal sepsis models an...

Background Human induced pluripotent stem cells represent a scalable source of youthful tissue progenitors and secretomes for regenerative therapies. The aim of our study was to investigate the potential of conditioned medium (CM) from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of human bone marrow-derived mes...

Aims The aim of this study was to create artificial intelligence (AI) software with the purpose of providing a second opinion to physicians to support distal radius fracture (DRF) detection, and to compare the accuracy of fracture detection of physicians with and without software support. Methods The dataset consisted of 26,121 anonymized anterior...

The vision of using bone adhesives for adjunct surgical treatment of complicated fractures or facile reattachment of bone fragments is highly attractive, as compared to conventional techniques, it is expected to significantly reduce operation times and potentially avoid the need for revision surgeries. Nevertheless, no commercial adhesives, that co...

Background The aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model. Methods 6 weeks after induction of osteoporosis...

A biotechnological platform consisting of two-color 3D super-resolution readout and a microfluidic system was developed to investigate platelet interaction with a layer of perfused endothelial cells under flow conditions. Platelet activation has been confirmed via CD62P clustering on the membrane and mitochondrial morphology of ECs at the single ce...

Mesenchymal stromal cells from the bone marrow (BMSCs) exhibit a functional decline during aging. We previously found that extracellular matrix (ECM) engineered from human induced pluripotent stem cell-derived mesenchymal progenitors enhances the osteogenic capacity of BMSCs. In the current study, we investigated how this ECM affects the three-line...

Cellular senescence has a profound effect on human physiology, including healing, cancer and aging. Here, we show that wounding causes surrounding keratinocytes, fibroblasts, and other skin cell types to rapidly become senescent, within minutes to hours. Mechanistically, the induction of senescence is transcription independent, utilizing pre-exi...

Muscle tissues attached to the proximal ends of hamstring tendon grafts are routinely discarded during anterior cruciate ligament (ACL) reconstruction. Preserving the muscle on the ACL graft was shown to improve the surgery outcomes, possibly due to the osteogenic differentiation of muscle satellite cells, accelerating graft integration into the un...

Regeneration of bone defects is often limited due to compromised bone tissue physiology. Previous studies suggest that engineered extracellular matrices enhance the regenerative capacity of mesenchymal stromal cells. In this study, we used human-induced pluripotent stem cells, a scalable source of young mesenchymal progenitors (hiPSC-MPs), to gener...

(1) Background: Uncontrolled inflammation often contributes to life-threatening sepsis sequela such as multi-organ dysfunction syndrome (MODS), and is accompanied by abnormal levels of pathological and damage-associated molecular patterns (PAMPs & DAMPs) in biological fluids. Activated carbon or charcoal (AC) of new generation with ameliorated bioc...

Environmental biophysical interactions are recognized to play an essential part in the human biological processes associated with trauma recovery. Many studies over several decades have furthered our understanding of the effects that Pulsed Electromagnetic Fields (PEMF) have on the human body, as well as on cellular and biophysical systems. These i...

Regeneration of bone defects in elderly patients is limited due to the decreased function of bone forming cells and compromised tissue physiology. Previous studies suggested that the regenerative activity of stem cells from aged tissues can be enhanced by exposure to young systemic and tissue microenvironments. The aim of our project was to investi...

Recent studies suggested that both the soluble protein of the mesenchymal stromal cell (MSC) secretome, as well as the secreted extracellular vesicles (EVs) promote bone regeneration. However, there is limited knowledge of the changes in MSC secretome vesicular fraction during aging. We therefore aimed to characterize the release profiles and cargo...

Mesenchymal stem cells (MSCs) have the potential to repair and regenerate damaged tissues in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. Previous studies suggested that the regenerative activity of stem cells can be enhanced by exposure to tissue microenvironments. The a...

The spatial boundaries of tissue response to wounding are unknown. Here, we show that in mammals, the ribosomal protein S6 (rpS6) is phosphorylated in response to skin injury, forming a zone of activation surrounding the region of the initial insult. This p-rpS6-zone forms within minutes after wounding and is present until healing is complete. The...

Chronic wounds remain a serious clinical problem with insufficient therapeutic approaches. In this study we investigated the dose dependency of rhVEGF165 in fibrin sealant in both ischemic and non-ischemic excision wounds using our recently developed impaired-wound healing model. An abdominal flap was harvested from the rat with unilateral ligation...

Photobiomodulation, showing positive effects on wound healing processes, has been performed mainly with lasers in the red/infrared spectrum. Light of shorter wavelengths can significantly influence biological systems. This study aimed to evaluate and compare the therapeutic effects of pulsed LED light of different wavelengths on wound healing in a...

An injectable hybrid hydrogel is synthesized, comprising silk fibroin (SF) and chondroitin sulfate (CS) through di‐tyrosine formation bond of SF chains. CS and SF are reported with excellent biocompatibility as tissue engineering scaffolds. Nonetheless, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate art...

Cardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limite...

Simple Summary Following tooth loss, the jaw bone undergoes gradual atrophy of the tooth-bearing alveolar process which poses a major challenge for dental implant therapy. In order to compensate for the decreasing bone height and bone volume in the upper jaw, bone graft particles can be inserted into the maxillary sinus (maxillary sinus floor augme...

Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds int...

It is unknown what the spatial boundaries of tissue response to wounding are. Here we show that in mammals the ribosomal protein S6 (rpS6) is phosphorylated in response to skin injury forming a zone of activation surrounding the region of the initial insult. This p-rpS6-zone forms within minutes after wounding and is present until healing is comple...

Background Zoledronic acid improves bone microarchitecture and biomechanical properties after chronic rotator cuff repair (RCR) in rats. Besides the positive effects of zoledronic acid on bone mineral density and bone microarchitecture, bisphosphonates have positive effects on skeletal muscle function. Purposes/Hypothesis The purposes of this stud...

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, anti...

Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT—applied wit...

Background: Zoledronic acid improves bone microarchitecture and biomechanical properties after rodent chronic rotator cuff repair (RCR). Besides the positive effects of zoledronic acid on bone microarchitecture, bisphosphonates have positive effects on skeletal muscle function according to the so-called “muscle-bone crosstalk”. Methods: A total of...

Fibrin hydrogels have proven highly suitable scaffold materials for skeletal muscle tissue engineering in the past. Certain parameters of those types of scaffolds, however, greatly affect cellular mechanobiology and therefore the myogenic outcome. The aim of this study was to identify the influence of apparent elastic properties of fibrin scaffolds...

Senescence is a cellular state which involves cell cycle arrest and a proinflammatory phenotype, and it has traditionally been associated with cellular and organismal aging. However, increasing evidence suggests key roles in tissue growth and regrowth, especially during development and regeneration. Conversely, cellular plasticity—the capacity of c...

Cardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limite...

Objective Implantation of tissue-engineered tracheal grafts represents a visionary strategy for the reconstruction of tracheal wall defects after resections and may develop into a last chance for a number of patients with severe cicatricial stenosis. The use of a decellularized tracheal substrate would offer an ideally stiff graft, but the matrix d...

Synthetic peptide conjugates that can molecularly target and activate blood platelets are designed for hemostasis applications. An engineered thrombin receptor-activating peptide (TRAP-Cys, SFLLRNPNC) is covalently attached to cell-compatible 8-arm poly (ethylene glycol) maleimides via Michael addition. It is proved that the ability of TRAP to acti...

Purpose The aim of this study was to investigate the effect of extracorporeal shockwave therapy (ESWT) on bone microstructure as well as the bone-tendon-interface and the musculo-tendinous transition zone to explain the previously shown improved biomechanics in a degenerative rotator cuff tear animal model. This study hypothesized that biomechanica...

The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. There...

Cartilage damage typically starts at its surface, either due to wear or trauma. Treatment of these superficial defects is important in preventing degradation and osteoarthritis (OA). Biomaterials currently used for deep cartilage defects lack appropriate properties for this application. Therefore, we investigated photo-crosslinked methacrylamide-mo...

NEOVASCULARIZATION STIMULATING HYDROGELS FOR REGENERATIVE MEDICINE

Background: There is critical unmet need for new vascularized tissues to support or replace injured tissues and organs. Various synthetic and natural materials were already established for use of 2D and 3D in vitro neovascularization assays, however, they still cannot mimic the complex functions of the sum of the extracellular matrix (ECM) in nativ...

Background: There is critical unmet need for new vascularized tissues to support or replace injured tissues and organs. Various synthetic and natural materials were already established for use of 2D and 3D in vitro neovascularization assays, however, they still cannot mimic the complex functions of the sum of the extracellular matrix (ECM) in nati...

A NOVEL HUMAN MATERIAL BASED PLATFORM TECHNOLOGY FOR TISSUE ENGINEERING This is the link to the supplemental video: https://youtu.be/cEArIBSnKsc

Tissue engineering is rapidly progressing toward clinical application. In the musculoskeletal field, there has been an increasing necessity for bone and cartilage replacement. Despite the promising translational potential of tissue engineering approaches, careful attention should be given to the quality of developed constructs to increase the real...

Design and development of novel nanobiomaterials with multifunctional properties hold the promise of new therapeutic strategies to improve the current clinical research in the field of tissue engineering and regenerative medicine. Here, we have successfully synthesized novel autofluorescent hydroxyapatite (HAP) using a template-assisted assembly pr...

Exposure to pathogens elicits a complex immune response involving multiple interdependent pathways. This response may mitigate detrimental effects and restore health but, if imbalanced, can lead to negative outcomes including sepsis. This complexity and need for balance pose a challenge for clinicians and have attracted attention from modelers seek...

Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosi...

Background The aims of this study are to determine (i) SARS-CoV-2 antibody positive employees in Austrian trauma hospitals and rehabilitation facilities, (ii) number of active virus carriers (symptomatic and asymptomatic) during the study, (iii) antibody decline in seropositive subjects over a period of around 6 months, (iv) the usefulness of rapid...

Introduction: Re-rupture rates after arthroscopic rotator cuff repair are reported up to 94%. Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bisphosphonates (e.g. zoledronic acid) show promising long-term results in osteoporosis therapy regarding increased bone mineral density and reduction of fract...

Coculture systems employing adipose tissue-derived mesenchymal stromal/stem cells (ASC) and endothelial cells (EC) represent a widely used technique to model vascularization. Within this system, cell-cell communication is crucial for the achievement of functional vascular network formation. Extracellular vesicles (EVs) have recently emerged as key...

Background This study aimed to investigate whether rodent shoulder specimens fixed in formaldehyde for histological and histomorphometric investigations and specimens stained using Lugol’s solution for soft tissue visualization by micro-computed tomography (microCT) are still eligible to be used for bone architecture analysis by microCT. Methods I...

After decades of simply being referred to as the body's sewage system, the lymphatic system has recently been recognized as a key player in numerous physiological and pathological processes. As an essential site of immune cell interactions, the lymphatic system is a potential target for next-generation drug delivery approaches in treatments for can...

Context: On March 11, the World Health Organization (WHO) announced the current corona virus disease 2019 (COVID-19) outbreak as a pandemic. The first laboratory-confirmed case of COVID-19 in Austria was announced on February 27, 2020. Since then, the incidence of infection followed an exponential increase until a complete lockdown in March 2020. T...

Reconstruction of bone defects and compensation of deficient repair mechanisms represent important goals within the field of regenerative medicine and require novel safe strategies for translation into the clinic. A non-viral osteogenic gene therapeutic vector system (‘hybrid vectors’) was generated, combining an improved bone morphogenetic protein...

Due to their strong biomimetic potential, silk fibroin (SF) hydrogels are impressive candidates for tissue engineering, due to their tunable mechanical properties, biocompatibility, low immunotoxicity, controllable biodegradability, and a remarkable capacity for biomaterial modification and the realization of a specific molecular structure. The fun...

Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane, which is the joint capsule's inner layer, is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bo...

Context: On March 11, the World Health Organization (WHO) announced the current corona virus disease 2019 (COVID-19) outbreak as a pandemic. The first laboratory-confirmed case of COVID-19 in Austria was announced on February 27, 2020. Since then, the incidence of infection followed an exponential increase until a complete lockdown in March 2020. T...

MicroRNAs regulate bone homeostasis and circulating microRNAs have been proposed as novel bone biomarkers. The effect of anti‐osteoporotic treatment on circulating microRNAs has not been described in detail. Therefore, we performed a comprehensive analysis of microRNA serum levels in OVX and SHAM rats over 12 weeks of anti‐resorptive or osteo‐anabo...

Background In spite of advances in the treatment of cartilage defects using cell and scaffold-based therapeutic strategies, the long-term outcome is still not satisfying since clinical scores decline years after treatment. Scaffold materials currently used in clinical settings have shown limitations in providing suitable biomechanical properties an...

Zusammenfassung: Um der Reduktion der Knochendichte am Oberarmkopf bei chronischen Rotatorenmanschettenrupturen entgegenzuwirken wurde der Effekt von Zoledronsäure in einem Rattenmodell untersucht. Bei insgesamt 32 männlichen Sprague-Dawley Ratten wurde eine unilaterale Tenotomie der Supraspinatussehne durchgeführt, drei Wochen später erhielten all...

This reference work presents the basic principles of angiogenesis induction, including the roles of signaling factors such as hypoxia-inducible factors, biophysical stimulation and angiogenic cells. The book also covers lymphogenesis induction. Both the established fundamentals in the field as well as new trends in the vascularization of engineered...

This article deliberates about the importance of polymer-based bioadhesive biomaterials’ medical application in healthcare and in redefining healthcare management. Nowadays, the application of bioadhesion in the health sector is one of the great interests for various researchers, due to recent advances in their formulation development. Actually, th...

Background The interest in non-manipulated cells originating from adipose tissue has raised tremendously in the field of tissue engineering and regenerative medicine. The resulting stromal vascular fraction (SVF) cells have been successfully used in numerous clinical applications. The aim of this experimental work is, first to combine a macroporous...

Hintergrund: Re-Rupturraten nach arthroskopischer Rotatorenmanschettenrekonstruktion werden mit bis zu 94% in der Literatur angegeben. Bei chronischen Rotatorenmanschettenrupturen findet sich häufig eine herabgesetzte Knochendichte im Oberarmkopf. Bei Osteoporose werden mit Bisphosphonaten (z.B. Zoledronsäure) hervorragende Langzeitergebnisse hinsi...

Silk fibroin (SF) hydrogels are impressive candidates with the strong biomimetic potential for tissue engineering due to their tunable mechanical properties, biocompatibility, low immune-toxicity, controllable biodegradability, and a remarkable capacity in the biomaterial modification and specific molecular structure. The fundamental chemical and p...

Bone marrow provides a rich source of mesenchymal stromal cells (MSCs), which have the remarkable capacity for cell and tissue regeneration. Since their initial discovery in the guinea pig almost 50 years ago, bone-marrow-derived MSCs have been extensively studied in animals and humans. Several subpopulations have been characterized with the aim to...

microRNAs are small and evolutionary conserved RNA molecules that vastly fine-tune protein expression at a posttranscriptional level. microRNA modulation has recently surfaced as powerhouse feeding the progress of novel strategies for tissue and cell engineering and regeneration. The field is growing exponentially each year and approaching clinical...

Background: Maxillary sinus floor augmentation (MSFA) is a well-established and predictable augmentation method in severely resorbed maxillae. However, data on the vertical course of bone graft consolidation within the maxillary sinus are rare. The aim of the present study was to quantify the vertical distribution of new bone formation in MSFA and...

Background Bone mineral density at the humeral head is reduced in patients with chronic rotator cuff tears. Bone loss in the humeral head is associated with repair failure after rotator cuff reconstruction. Bisphosphonates (eg, zoledronic acid) increase bone mineral density. Hypothesis Zoledronic acid improves bone mineral density of the humeral h...

Biomechanical cues such as shear stress, stretching, compression, and matrix elasticity are vital in the establishment of next generation physiological in vitro tissue models. Matrix elasticity, for instance, is known to guide stem cell differentiation, influence healing processes and modulate extracellular matrix (ECM) deposition needed for tissue...

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrate...

Background To date, the significant osteoinductive potential of bone morphogenetic protein 2 (BMP-2) non-viral gene therapy cannot be fully exploited therapeutically. This is mainly due to weak gene delivery and brief expression peaks restricting the therapeutic effect. Objective Our objective was to test the application of minicircle DNA, allowin...

Purinergic P2 receptors are critical regulators of several functions within the vascular system, including platelet aggregation, vascular inflammation, and vascular tone. However, a role for ATP release and P2Y receptor signalling in angiogenesis remains poorly defined. Here, we demonstrate that blood vessel growth is controlled by P2Y2 receptors....

Background: A great extent of knowledge on peripheral nerve regeneration has been gathered using the rat sciatic nerve model. The femoral nerve model of the rat offers an interesting alternative, as it lacks disadvantageous features such as automutilation. For the analysis of locomotor behavior in rats after sciatic nerve injury, the CatWalk™ XT Ga...

Background and aim: The gold standard for peripheral nerve regeneration uses a sensory autograft to bridge a motor/sensory defect site. For motor nerves to regenerate, Schwann cells (SC) myelinate the newly grown axon. Sensory SCs have a reduced ability to produce myelin, partially explaining low success rates of autografts. This issue is masked i...

Surgical sealants help achieve rapid haemostasis when applied as an adjunct to sutures in vascular surgery, but their use can lead to various side effects. This study compared the local inflammatory reaction to commercially available BioGlue and Coseal sealants in a rabbit aorta suture hole model. Twenty male New Zealand white rabbits were randomis...

This reference work presents the origins of cells for tissue engineering and regeneration, including primary cells, tissue-specific stem cells, pluripotent stem cells and trans-differentiated or reprogrammed cells. There is particular emphasis on current understanding of tissue regeneration based on embryology and evolution studies, including mecha...

Effective regeneration of bone defects often presents significant challenges, particularly in patients with decreased tissue regeneration capacity due to extensive trauma, disease, and/or advanced age. A number of studies have focused on enhancing bone regeneration by applying mesenchymal stromal cells (MSCs) or MSC-based bone tissue engineering st...