Optimization of extracellular matrix production from human induced pluripotent stem cell-derived fibroblasts for scaffold fabrication for application in wound healing.

Extracellular matrix is a key component of all tissues, including skin and it plays a crucial role in the complex events of wound healing. These events are impaired in chronic wounds, with chronic inflammation and infection often present in these non-healing wounds. Many tissue engineering approaches for wound healing provide a scaffold to mimic the native matrix.

Hydroxyapatite Particle Shape and Size Influence MSC Osteogenesis by Directing the Macrophage Phenotype in Collagen-Hydroxyapatite Scaffolds.

The field of bone tissue engineering has seen the advancement of a variety of biomaterials with a diverse range of material properties. Biomaterial properties such as particle shape and size, stiffness, and pore size all influence the osteogenic capacity of biomaterials, typically evaluated by analyzing their potential to promote osteogenesis in mesenchymal stem cells (MSCs). There is now accumulating evidence highlighting the role of macrophages in driving bone regeneration responses.

Substrate Stiffness Modulates the Crosstalk Between Mesenchymal Stem Cells and Macrophages.

Upon implantation of a biomaterial, mesenchymal stem cells (MSCs) and macrophages contribute to the wound healing response and the regeneration cascade. Although biomaterial properties are known to direct MSC differentiation and macrophage polarization, the role of biomaterial cues, specifically stiffness, in directing the crosstalk between the two cell types is still poorly understood. This study aimed to elucidate the role of substrate stiffness in modulating the immunomodulatory properties of MSCs and to shed light on their complex interactions with macrophages when presented with diverse biomaterial stiffness cues, a situation analogous to the implant environment where multiple cell types interact with an implanted biomaterial to determine regenerative outcomes.

Collagen/GAG scaffolds activated by RALA-siMMP-9 complexes with potential for improved diabetic foot ulcer healing.

Impaired wound healing of diabetic foot ulcers has been linked to high MMP-9 levels at the wound site. Strategies aimed at the simultaneous downregulation of the MMP-9 level in situ and the regeneration of impaired tissue are critical for improved diabetic foot ulcer (DFU) healing. To fulfil this aim, collagen/GAG (Col/GAG) scaffolds activated by MMP-9-targeting siRNA (siMMP-9) were developed in this study.

Scaffolds Functionalized with Matrix from Induced Pluripotent Stem Cell Fibroblasts for Diabetic Wound Healing.

Diabetic foot ulcers (DFUs) are chronic wounds, with 20% of cases resulting in amputation, despite intervention. A recently approved tissue engineering product-a cell-free collagen-glycosaminoglycan (GAG) scaffold-demonstrates 50% success, motivating its functionalization with extracellular matrix (ECM). Induced pluripotent stem cell (iPSC) technology reprograms somatic cells into an embryonic-like state.

The Use of Genipin as an Effective, Biocompatible, Anti-Inflammatory Cross-Linking Method for Nerve Guidance Conduits.

A number of natural polymer biomaterial-based nerve guidance conduits (NGCs) are developed to facilitate repair of peripheral nerve injuries. Cross-linking ensures mechanical integrity and desired degradation properties of the NGCs; however, common methods such as formaldehyde are associated with cellular toxicity. Hence, there is an unmet clinical need for alternative nontoxic cross-linking agents.

Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential.

Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively.

Material stiffness influences the polarization state, function and migration mode of macrophages.

Biomaterial implantation is followed by an inflammatory cascade dominated by macrophages, which determine implant acceptance or rejection through pro- and anti-inflammatory polarization states (Anderson et al., 2008; Brown and Badylak, 2013). It is known that chemical signals such as bacterial endotoxins and cytokines (IL4) can direct macrophage polarization (Mantovani et al.

Macrophage Polarization in Response to Collagen Scaffold Stiffness Is Dependent on Cross-Linking Agent Used To Modulate the Stiffness.

Macrophages are the first responders to biomaterial implantation and determine the success or failure of an implant through their polarization into proinflammatory (M1) and anti-inflammatory (M2) states. It is known that material properties such as stiffness can influence this response, with these properties typically modulated using a cross-linking agent. However, the cellular response comparing different cross-linking agents is often not analyzed.

The shape and size of hydroxyapatite particles dictate inflammatory responses following implantation.

The extent of regeneration following biomaterial implantation is dependent on the microenvironment surrounding the implant. Since implant composition can have a profound effect on inflammation, it is essential to understand this process as a non-resolving inflammatory response can lead to fibrous encapsulation and insufficient integration. Incorporation of particulates into implants confers structural and functional benefits, thus optimizing particulate characteristics to enhance immune mediated efficacy is important.

Decellularized grafts with axially aligned channels for peripheral nerve regeneration.

At least 2 million people worldwide suffer annually from peripheral nerve injuries (PNI), with estimated costs of $7 billion incurred due to paralysis alone. The current "gold" standard for treatment of PNI is the autograft, which poses disadvantages such as high fiscal cost, possible loss of sensation at donor site and the requirement of two surgeries. Allografts are viable alternatives; however, intensive immunosuppressive treatments are often necessary to prevent host rejection.

Bioengineering tools to elucidate and control the fate of transplanted stem cells.

For the last decade, stem cell therapies have demonstrated enormous potential for solving some of the most tragic illnesses, diseases and tissue defects worldwide. Currently, more than 1300 clinical trials use stem cell therapy to solve a spectrum of cardiovascular, neurodegenerative and autoimmune diseases (http://www.clinicaltrials.

Effect of introducing a short amyloidogenic sequence from the Aβ peptide at the N-terminus of 18-residue amphipathic helical peptides.

Fibril formation is the hallmark of pathogenesis in Alzheimer's disease and other amyloid disorders caused by conformational alterations leading to the aggregation of soluble monomers. Aβ40 self-associates to form amyloid fibrils. Its central seven-residue segment KLVFFAE (Aβ16-22), which is thought to be crucial for fibril formation of the full-length peptide, forms fibrils even in isolation.

Engineered cell homing.

One of the greatest challenges in cell therapy is to minimally invasively deliver a large quantity of viable cells to a tissue of interest with high engraftment efficiency. Low and inefficient homing of systemically delivered mesenchymal stem cells (MSCs), for example, is thought to be a major limitation of existing MSC-based therapeutic approaches, caused predominantly by inadequate expression of cell surface adhesion receptors. Using a platform approach that preserves the MSC phenotype and does not require genetic manipulation, we modified the surface of MSCs with a nanometer-scale polymer construct containing sialyl Lewis(x) (sLe(x)) that is found on the surface of leukocytes and mediates cell rolling within inflamed tissue.