Madeline C. Cramer

Bio: Madeline C. Cramer is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Extracellular matrix & Self-healing hydrogels. The author has an hindex of 9, co-authored 13 publications receiving 602 citations. Previous affiliations of Madeline C. Cramer include Carnegie Mellon University.

Extracellular Matrix-Based Biomaterials and Their Influence Upon Cell Behavior.

Abstract: Biologic scaffold materials composed of allogeneic or xenogeneic extracellular matrix (ECM) are commonly used for the repair and remodeling of injured tissue. The clinical outcomes associated with implantation of ECM-based materials range from unacceptable to excellent. The variable clinical results are largely due to differences in the preparation of the material, including characteristics of the source tissue, the method and efficacy of decellularization, and post-decellularization processing steps. The mechanisms by which ECM scaffolds promote constructive tissue remodeling include mechanical support, degradation and release of bioactive molecules, recruitment and differentiation of endogenous stem/progenitor cells, and modulation of the immune response toward an anti-inflammatory phenotype. The methods of ECM preparation and the impact of these methods on the quality of the final product are described herein. Examples of favorable cellular responses of immune and stem cells associated with constructive tissue remodeling of ECM bioscaffolds are described.

Immunomodulation and Mobilization of Progenitor Cells by Extracellular Matrix Bioscaffolds for Volumetric Muscle Loss Treatment

Abstract: Acellular bioscaffolds composed of extracellular matrix (ECM) have been effectively used to promote functional tissue remodeling in both preclinical and clinical studies of volumetric muscle loss, but the mechanisms that contribute to such outcomes are not fully understood Thirty-two C57bl/6 mice were divided into eight groups of four animals each A critical-sized defect was created in the quadriceps muscle and was repaired with a small intestinal submucosa ECM bioscaffold or left untreated Animals were sacrificed at 3, 7, 14, or 56 days after surgery The spatiotemporal cellular response in both treated and untreated groups was characterized by immunolabeling methods Early time points showed a robust M2-like macrophage phenotype following ECM treatment in contrast to the predominant M1-like macrophage phenotype present in the untreated group ECM implantation promoted perivascular stem cell mobilization, increased presence of neurogenic progenitor cells, and was associated with myotube formation These cell types were present not only at the periphery of the defect near uninjured muscle, but also in the center of the ECM-filled defect ECM bioscaffolds modify the default response to skeletal muscle injury, and provide a microenvironment conducive to a constructive healing response

Extracellular Matrix Bioscaffolds for Building Gastrointestinal Tissue

Abstract: Regenerative medicine is a rapidly advancing field that uses principles of tissue engineering, developmental biology, stem cell biology, immunology, and bioengineering to reconstruct diseased or damaged tissues. Biologic scaffolds composed of extracellular matrix have shown great promise as an inductive substrate to facilitate the constructive remodeling of gastrointestinal (GI) tissue damaged by neoplasia, inflammatory bowel disease, and congenital or acquired defects. The present review summarizes the preparation and use of extracellular matrix scaffolds for bioengineering of the GI tract, identifies significant advances made in regenerative medicine for the reconstruction of functional GI tissue, and describes an emerging therapeutic approach.

Nanoparticle–Hydrogel Composites: Concept, Design, and Applications of These Promising, Multi‐Functional Materials

Abstract: New technologies rely on the development of new materials, and these may simply be the innovative combination of known components. The structural combination of a polymer hydrogel network with a nanoparticle (metals, non-metals, metal oxides, and polymeric moieties) holds the promise of providing superior functionality to the composite material with applications in diverse fields, including catalysis, electronics, bio-sensing, drug delivery, nano-medicine, and environmental remediation. This mixing may result in a synergistic property enhancement of each component: for example, the mechanical strength of the hydrogel and concomitantly decrease aggregation of the nanoparticles. These mutual benefits and the associated potential applications have seen a surge of interest in the past decade from multi-disciplinary research groups. Recent advances in nanoparticle-hydrogel composites are herein reviewed with a focus on their synthesis, design, potential applications, and the inherent challenges accompanying these exciting materials.

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

Abstract: The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell–microenvironment interactions continue to overturn much earl...

Extracellular matrix-based materials for regenerative medicine

Abstract: In tissue engineering and regenerative medicine, a biomaterial provides mechanical support and biochemical signals to encourage cell attachment and modulate cell behaviour. Nature’s template for a biomaterial is the extracellular matrix (ECM). The ECM contains intrinsic biochemical and mechanical cues that regulate cell phenotype and function in development, in homeostasis and in response to injury. The use of ECM-based materials in biomedical research has advanced from coating cell culture plates with purified ECM components to the design of ECM-mimicking biomaterials and the engineering of decellularized tissues aimed at recapitulating the dynamics, composition and structure of the ECM. In this Review, we highlight important matrix properties and functions in the context of tissue engineering and regenerative medicine, consider techniques such as proteomics for the investigation of matrix structure and composition and discuss different engineering strategies for the design of matrix-mimicking biomaterials. Tissue, whole organ and cell culture decellularization approaches are examined for their potential to preserve the tissue-specific biochemical composition and ultrastructure of the ECM and for the development of biomaterials that promote the formation of functional tissues in clinical applications. Finally, we investigate challenges and opportunities of ECM biomaterials for the design of organotypic models to study disease progression, for the ex vivo creation of engineered tissue and for the clinical translation of functional tissue reconstruction strategies in vivo. The extracellular matrix is nature’s template for an ideal biomaterial to guide tissue homeostasis and repair. In this Review, matrix-mimicking biomaterials and decellularized matrices are discussed for their potential to reconstruct and repair tissues in vitro and in vivo.

Overview of natural hydrogels for regenerative medicine applications

Abstract: Hydrogels from different materials can be used in biomedical field as an innovative approach in regenerative medicine. Depending on the origin source, hydrogels can be synthetized through chemical and physical methods. Hydrogel can be characterized through several physical parameters, such as size, elastic modulus, swelling and degradation rate. Lately, research is focused on hydrogels derived from biologic materials. These hydrogels can be derived from protein polymers, such as collage, elastin, and polysaccharide polymers like glycosaminoglycans or alginate among others. Introduction of decellularized tissues into hydrogels synthesis displays several advantages compared to natural or synthetic based hydrogels. Preservation of natural molecules such as growth factors, glycans, bioactive cryptic peptides and natural proteins can promote cell growth, function, differentiation, angiogenesis, anti-angiogenesis, antimicrobial effects, and chemotactic effects. Versatility of hydrogels make possible multiple applications and combinations with several molecules on order to obtain the adequate characteristic for each scope. In this context, a lot of molecules such as cross link agents, drugs, grow factors or cells can be used. This review focuses on the recent progress of hydrogels synthesis and applications in order to classify the most recent and relevant matters in biomedical field.

Design of biodegradable, implantable devices towards clinical translation

Abstract: Biodegradable materials, including natural and synthetic polymers and hydrolyzable metals, constitute the main components of temporary, implantable medical devices. Besides the intrinsic properties of the materials, the most critical factor determining the successful clinical outcome of implantable and degradable devices is the host response, particularly the immune response, which largely depends on the material features and degradation mechanisms. In this Review, we first survey the state of the art in terms of materials options for use in biodegradable medical devices, focusing on degradation mechanisms and their control. In particular, we highlight silk, which is emerging as an important polymer, owing to its mechanical robustness, bioactive component sequestration, degradability without problematic metabolic products and biocompatibility. We then discuss the host response to these biodegradable materials in terms of dynamic tissue–implant interfaces. Next, we examine the clinical translation of three leading biodegradable material systems — natural and synthetic biodegradable polymers and biodegradable metals — and the related challenges in the context of orthopaedic fixation devices, cardiovascular stents and biodegradable electronic devices. Looking to the future, we propose updated material design strategies to improve the clinical outcomes for these biodegradable medical devices. Clinical outcomes with implantable and degradable devices largely depend on host response. This Review surveys material options and degradation mechanisms relevant to host responses to biodegradable devices, examines clinical translation of leading biodegradable materials and proposes updated material-design strategies to improve device performance.