Jon Kluge

University of Pennsylvania | UP

There is a large unmet need for off-the-shelf biomaterial options to supplant venous autografts in bypass and reconstructive surgical procedures. Existing graft alternatives formed from non-degradable synthetic polymers are not capable of maintaining long-term patency and are thus not indicated for <6 mm inner diameter bypass procedures. To fill th...

The use of mRNA and miRNA as diagnostic parameters and therapeutic agents has drawn wide interest both clinically and in research. However, RNA is a labile molecule, which requires strict storage conditions, often including cold temperatures or dry environments, in order to preserve RNA integrity. Achieving this requires huge costs for storage and...

Preliminary studies have shown that silk fibroin protein can protect biomacromolecules from thermal degradation, but the deeper understanding of underlying mechanisms needed to fully leverage the stabilizing potential of this matrix has not been realized. In this study, we investigate stabilization of plasma C-reactive protein, a diagnostic biomark...

The fabrication of cellulose-spider silk bio-nanocomposites comprised of cellulose nanocrystals (CNCs) and recombinant spider silk protein fused to a cellulose binding domain (CBD) is described. Silk-CBD successfully binds cellulose, and unlike recombinant silk alone, silk-CBD self-assembles into microfibrils even in the absence of CNCs. Silk-CBD-C...

Significance Both research and clinical care often require blood to be collected away from the laboratory setting. Remote collection presents a logistical and financial challenge, as it requires continuous access to portable cold storage. Although there has been a thrust to develop means to bypass the cold chain, available technologies such as drie...

Storage of silk proteins in liquid form can lead to excessive waste from premature gelation, thus an alternative storage strategy is proposed using lyophilization to generate soluble and shelf-stable powder formats for on-demand use. Initial solution stability studies highlighted instabilities of higher-molecular-weight silks that could not be reso...

Silk fibroin is a high molecular weight amphiphilic protein that self-assembles into robust biomaterials with remarkable properties including stabilization of biologicals and tunable release kinetics correlated to processing conditions. Cells, antibiotics, monoclonal antibodies and peptides, among other biologics, have been encapsulated in silk usi...

Biomaterial substrates composed of aligned electrospun fibers are attractive supports for the regeneration of connective tissues because the fibers mimic the micro-architecture of connective tissues, are durable under cyclic tensile loads, and can guide cell adhesion, orientation, and gene expression. Previous studies have shown that both the fiber...

Sutureless anastomosis devices are designed to reduce surgical time and difficulty, which may lead to quicker and less invasive cardiovascular anastomosis. The implant uses a barb-and-seat compression fitting composed of one male and two female components. The implant body is resorbable and capable of eluting heparin. Custom robotic deposition equi...

Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative medicine due the capacity of platelet-derived growth factors to accelerate and direct healing processes. However, limitations to this approach include poor mechanical properties, relatively rapid degradation, and the lack of control of release of growth fa...

The mechanical properties of spider silks drive interest as sources of new materials. However, there remains a lot to learn regarding the relationships between sequence, structure, and mechanical properties. In order to predict the types of sequence–functional relationships, synthesis–characterization–computation are integrated using recombinant sp...

Degeneration of the intervertebral disc (IVD) represents a significant muscular skeletal disease. Recently, scaffolds composed of synthetic, natural and hybrid biomaterials have been investigated as options to restore the IVD; however, they lack the hallmark lamellar morphological features of annulus fibrosus (AF) tissue. The goal of regenerating t...

Synthetic/biopolymer composite scaffolds can provide improved flexibility when designing optimized stem-cell-laden tissue repair devices for fiber-reinforced tissues. Composites enable a range of mechanical properties, rates of degradation, and other functional attributes of a degradable scaffold to be finely tuned by modifying polymer sources and...

This chapter describes the mechanical determinants for developing tissues. Cells within living tissues transduce mechanical forces by using a variety of mechanisms. Although the signaling processes of mechanotransduction are complex, involving many different molecules and pathways, they may be activated by similar mechanisms in response to a variet...

An important challenge in the biomaterials field is to mimic the structure of functional tissues via cell and extracellular matrix (ECM) alignment and anisotropy. Toward this goal, silk-based scaffolds resembling bone lamellar structure were developed using a freeze-drying technique. The structure could be controlled directly by solute concentratio...

Load-bearing porous biodegradable scaffolds are required to engineer functional tissues such as bone. Mechanical improvements to porogen leached scaffolds prepared from silk proteins were systematically studied through the addition of silk particles in combination with silk solution concentration, exploiting interfacial compatibility between the tw...

Fibrocartilaginous tissues such as the meniscus and annulus fibrosus serve critical load-bearing roles, relying on arrays of highly organized collagen fibers to resist tensile loads [1]. As these specialized structures are often injured, there exists great demand for engineered tissues for repair or replacement. Cell-laden aligned nanofibrous scaff...

Screening of biomaterial and tissue systems in vitro, for guidance of performance in vivo, remains a major requirement in the field of tissue engineering. It is critical to understand how culture stimulation affects both tissue construct maturation and function, with the goal of eliminating resource-intensive trial-and-error screening and better ma...

Silk fibroin protein is biodegradable and biocompatible, exhibiting excellent mechanical properties for various biomedical applications. However, porous three-dimensional (3-D) silk fibroin scaffolds, or silk sponges, usually fall short in matching the initial mechanical requirements for bone tissue engineering. In the present study, silk sponge ma...

To restore physiological function through regenerative medicine, biomaterials introduced into the body must degrade at a rate that matches new tissue formation. For effective therapies, it is essential that we understand the interaction between physiological factors, such as routine mechanical loading specific to sites of implantation, and the resu...

Vascular surgeries such as coronary artery bypass require small diameter vascular grafts with properties that are not available at this time. Approaches using synthetic biomaterials have been not completely successful in producing non-thrombogenic grafts with inner diameters less than 6 mm, and there is a need for new biomaterials and graft designs...

A modular approach to engineering cross-linked elastic biomaterials is presented for fine-tuning of material mechanical and biological properties. The three components, soluble elastin, hyaluronic acid, and silk fibroin, contribute with different features to the overall properties of the final material system. The elastic biomaterial is chemically...

Silk fibroin is a useful protein polymer for biomaterials and tissue engineering. In this work, porogen leached scaffolds prepared from aqueous and HFIP silk solutions were reinforced through the addition of silk particles. This led to about 40 times increase in the specific compressive modulus and the yield strength of HFIP‐based scaffolds. This i...

Effects of hydration on silk fibroin film properties were investigated for water‐annealed and MeOH‐treated samples. Hydration increased thickness by 60% for MeOH‐immersed films, while water‐annealed samples remained constant. MeOH‐immersed films showed an 80% mass loss due to water, while water‐annealed lost only 40%. O 2 permeability was higher in...

Hydrogels have mechanical properties and structural features that are similar to load-bearing soft tissues including intervertebral disc and articular cartilage, and can be implanted for tissue restoration or for local release of therapeutic factors. To help predict their performance, mechanical characterization and mathematical modeling are the av...

Restoration of a three-dimensional shape with soft tissue augmentation is a challenge for surgical reconstruction and esthetic improvement of intraoral mucosa and perioral skin tissues. A connective tissue graft or free gingival graft, classically used for such indications, requires a donor site, which may lead to various clinical complications. In...

We directly prepared insoluble silk films by blending with glycerol and avoiding the use of organic solvents. The ability to blend a plasticizer like glycerol with a hydrophobic protein like silk and achieve stable material systems above a critical threshold of glycerol is an important new finding with importance for green chemistry approaches to n...

Water-insoluble regenerated silk materials are normally produced by increasing the beta-sheet content (silk II). In the present study water-insoluble silk films were prepared by controlling the very slow drying of Bombyx mori silk solutions, resulting in the formation of stable films with a predominant silk I instead of silk II structure. Wide angl...

Hydrogels have mechanical and structural properties similar to some tissues and extracellular matrices and can be implanted for tissue restoration or for local release of therapeutic factors. Of particular interest in our lab is the mechanical characterization of a novel class of sonication-induced silk protein hydrogels such that their performance...

We investigated how exogenous and endogenous glucocorticoids affect feather replacement in European starlings (Sturnus vulgaris) after approximately 56% of flight feathers were removed. We hypothesized that corticosterone would retard feather regrowth and decrease feather quality. After feather regrowth began, birds were treated with exogenous cort...

Spider silks are characterized by remarkable diversity in their chemistry, structure and functions, ranging from orb web construction to adhesives and cocoons. These unique materials have prompted efforts to explore potential applications of spider silk equivalent to those of silkworm silks, which have undergone 5,000 years of domestication and hav...

Purified native silk fibroin forms beta-sheet-rich, physically cross-linked, hydrogels from aqueous solution, in a process influenced by environmental parameters. Previously we reported gelation times of days to weeks for aqueous native silk protein solutions, with high ionic strength and temperature and low pH responsible for increasing gelation k...

Electrospinning was used to fabricate non-woven nanofibrous tubular scaffolds from Bombyx mori silk fibroin using an all aqueous process. Cell studies and mechanical characterization tests were performed on the electrospun silk tubes to assess the viability of their usage in bioengineering small-diameter vascular grafts. Human endothelial cells and...