Mechano-Chemical Effect of Gelatin- and HA-Based Hydrogels on Human Retinal Progenitor Cells.

Engineering matrices for cell therapy requires design criteria that include the ability of these materials to support, protect and enhance cellular behavior in vivo. The chemical and mechanical formulation of the biomaterials can influence not only target cell phenotype but also cellular differentiation. In this study, we have demonstrated the effect of a gelatin (Gtn)-hyaluronic acid (HA) hydrogel on human retinal progenitor cells (hRPCs) and show that by altering the mechanical properties of the materials, cellular behavior is altered as well.

Platelet-Rich Plasma Lysate-Incorporating Gelatin Hydrogel as a Scaffold for Bone Reconstruction.

In implant dentistry, large vertical and horizontal alveolar ridge deficiencies in mandibular and maxillary bone are challenges that clinicians continue to face. One of the limitations of porous blocks for reconstruction of bone in large defects in the oral cavity, and in the musculoskeletal system, is that fibrin clot does not adequately fill the interior pores and does not persist long enough to accommodate cell migration into the center of the block. The objective of our work was to develop a gelatin-based gel incorporating platelet-rich plasma (PRP) lysate, to mimic the role that a blood clot would normally play to attract and accommodate the migration of host osteoprogenitor and endothelial cells into the scaffold, thereby facilitating bone reconstruction.

A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the enhancement of retinal ganglion cells replacement therapy.

Biomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN.

An Injectable Multifunctional Dual-Phase Bead-Reinforced Gelatin Matrix Permissive of Mesenchymal Stem Cell Infiltration for Musculoskeletal Soft Tissue Repair.

This study develops a novel strategy for regenerative therapy of musculoskeletal soft tissue defects using a dual-phase multifunctional injectable gelatin-hydroxyphenyl propionic acid (Gtn-HPA) composite. The dual-phase gel consists of stiff, degradation-resistant, ≈2-mm diameter spherical beads made from 8 wt% Gtn-HPA in a 2 wt% Gtn-HPA matrix. The results of a 3D migration assay show that both the cell number and migration distance in the dual-phase gel system are comparable with the 2 wt% mono-phase Gtn-HPA, but notably significantly higher than for 8 wt% mono-phase Gtn-HPA (into which few cells migrated).

Observation of Collagen-Containing Lesions After Hematoma Resolution in Intracerebral Hemorrhage.

Background And Purpose: The classic presentation of chronic (stage III) hemorrhagic stroke lesions is a fluid-filled cavity. In one of the most commonly used animal models of intracerebral hemorrhage (ICH), we noticed additional solid material within the chronic lesion. We examined the composition of those chronic ICH lesions and compared them with human autopsy cases.

Platelet-Derived Growth Factor Stimulated Migration of Bone Marrow Mesenchymal Stem Cells into an Injectable Gelatin-Hydroxyphenyl Propionic Acid Matrix.

Bone marrow mesenchymal stem cells (bMSCs) are responsible in the repair of injured tissue through differentiation into multiple cell types and secretion of paracrine factors, and thus have a broad application profile in tissue engineering/regenerative medicine, especially for the musculoskeletal system. The lesion due to injury or disease may be a closed irregular-shaped cavity deep within tissue necessitating an injectable biomaterial permissive of host (endogenous) cell migration, proliferation and differentiation. Gelatin-hydroxyphenyl propionic acid (Gtn-HPA) is a natural biopolymer hydrogel which is covalently cross-linked by horseradish peroxidase (HRP) and hydrogen peroxide (HO) in situ and can be delivered to the lesion by needle injection.

Controlling Growth Factor Diffusion by Modulating Water Content in Injectable Hydrogels.

Recent advancements in the delivery of therapeutics for retinal diseases include the development of injectable hydrogels, networks of one or more hydrophilic polymers that contain a high-volume fraction of water. These systems are of particular interest due to their biocompatibility, permeability to water-soluble metabolites, and function as minimally invasive injectable delivery vehicles. Recently, hydrogels for ophthalmic applications have been developed that display a controlled release of factors necessary for cellular survival and proliferation.

The effects of shock wave stimulation of mesenchymal stem cells on proliferation, migration, and differentiation in an injectable gelatin matrix for osteogenic regeneration.

The treatment of a variety of defects in bony sites could benefit from mitogenic stimulation of osteoprogenitor cells, including endogenous bone marrow-derived mesenchymal stem cells (bMSCs), and from provision of such cells with a matrix permissive of their migration, proliferation, and osteogenic differentiation. That such MSC stimulation could result from treatment with noninvasive (extracorporeal) shock waves (ESWs), and the matrix delivered by injection could enable this therapeutic approach to be employed for applications in which preformed scaffolds and growth factor therapy are difficult to deploy. The objectives of the present study were to investigate focused ESWs for their effects on proliferation, migration, and osteogenic differentiation in an injectable gelatin (Gtn) matrix capable of undergoing covalent cross-linking in vivo.

Translational relevance of the goat as a preclinical model of the human labrum and chondrolabral junction-histological study.

The purpose of this study was to evaluate the histologic features of the caprine labrum, with emphasis on the chondrolabral junction, with the goal of informing the feasibility of the goat as an animal model. The left hip joint of six adolescent Spanish goats (Capra pyrenaica) was harvested and subjected to anatomical and histological assessments. Human acetabular and femoral head samples, collected during total hip arthroplasty, served as comparison samples.

Promoting Neuro-Supportive Properties of Astrocytes with Epidermal Growth Factor Hydrogels.

Biomaterials provide novel platforms to deliver stem cell and growth factor therapies for central nervous system (CNS) repair. The majority of these approaches have focused on the promotion of neural progenitor cells and neurogenesis. However, it is now increasingly recognized that glial responses are critical for recovery in the entire neurovascular unit.

Extracorporeal Shock Wave Stimulates Angiogenesis and Collagen Production in Facial Soft Tissue.

Background: This study investigated the efficacy of extracorporeal shock wave (ESW) application in stimulating dermal thickness, vascularity, and collagen synthesis of facial skin in a large animal model.

Materials And Methods: The facial skin of the maxillary and mandibular areas of goats (n = 6 per group) was treated with ESWs of different intensities (0.15 and 0.

Hydrogel-Based Therapy for Brain Repair After Intracerebral Hemorrhage.

We assessed an injectable gelatin hydrogel containing epidermal growth factor (Gtn-EGF) as a therapy for intracerebral hemorrhage (ICH). ICH was induced in rats via collagenase injection into the striatum. Two weeks later, Gtn-EGF was injected into the cavitary lesion.

In Situ Cross-linking Hydrogel as a Vehicle for Retinal Progenitor Cell Transplantation.

One of the current limitations of retinal transplantation of stem cells as well as other cell types is the dispersion of cells from the injection site (including loss of cells into the vitreous chamber) and low survival after transplantation. Gelatin-hydroxyphenyl propionic acid (Gtn-HPA) conjugate is a biodegradable polymer that can undergo covalent cross-linking , allowing for injection of incorporated cells through a small caliber needle followed by gel formation . We tested the hypothesis that Gtn-HPA hydrogel supports survival and integration of retinal progenitor cells (RPCs) post-transplantation.

EMSCs Build an All-in-One Niche via Cell-Cell Lipid Raft Assembly for Promoted Neuronal but Suppressed Astroglial Differentiation of Neural Stem Cells.

The therapeutic efficiency of allogenic/intrinsic neural stem cells (NSCs) after spinal cord injury is severely compromised because the hostile niche at the lesion site incurs massive astroglial but not neuronal differentiation of NSCs. Although many attempts are made to reconstruct a permissive niche for nerve regeneration, solely using a living cell material to build an all-in-one, multifunctional, permissive niche for promoting neuronal while inhibiting astroglial differentiation of NSCs is not reported. Here, ectomesenchymal stem cells (EMSCs) are reported to serve as a living, smart material that creates a permissive, all-in-one niche which provides neurotrophic factors, extracellular matrix molecules, cell-cell contact, and favorable substrate stiffness for directing NSC differentiation.

Tc-Methyl-Diphosphonate Binding to Mineral Deposits in Cultures of Marrow-Derived Mesenchymal Stem Cells in Osteogenic Medium.

The work is notable for describing a highly sensitive, quantitative, and nondestructive method for evaluating the in vitro amount of mineral accompanying different types of osteogenic differentiation of mesenchymal stem cells in a monolayer cell culture. What is so unique and useful about the method is that it has the potential to be used to define the kinetics of the differentiation process, reflected in the mineralization, without destroying the monolayer. Therefore, it remains intact for further experiments.

Photoluminescent Cationic Carbon Dots as efficient Non-Viral Delivery of Plasmid SOX9 and Chondrogenesis of Fibroblasts.

With the increasing demand for higher gene carrier performance, a multifunctional vector could immensely simplify gene delivery for disease treatment; nevertheless, the current non- viral vectors lack self-tracking ability. Here, a type of novel, dual-functional cationic carbon dots (CDs), produced through one-step, microwave-assisted pyrolysis of arginine and glucose, have been utilized as both a self-imaging agent and a non-viral gene vector for chondrogenesis from fibroblasts. The cationic CDs could condense the model gene plasmid SOX9 (pSOX9) to form ultra-small (10-30 nm) nanoparticles which possessed several favorable properties, including high solubility, tunable fluorescence, high yield, low cytotoxicity and outstanding biocompatibility.

Biomedical materials to meet the challenges of the aging epidemic.

The number and percentage of people throughout the world who will be 60 years of age and older are steadily growing due to reduced fertility rate and longer life expectancy. We are facing the prospect that large numbers of individuals in countries throughout the world will be living longer with disability and pain resulting from age-related disorders. We have a wide array of biomedical materials that could serve as the basis for treatments to deal with these problems.

No effect of topical application of tranexamic acid on articular cartilage.

Purpose: The objective of this study was to evaluate potential cytotoxicity of TXA on articular cartilage by assessing chondrocyte viability of osteochondral explants after exposure to different concentrations and durations of TXA.

Methods: Thirty-nine osteochondral plugs (OCPs) were harvested from three adult Yucatan minipigs immediately after their death. OCPs were divided into 13 groups exposed to different concentrations of TXA (1, 2 and 4 mg/ml in saline solution) for 1, 3 and 6 h.

Porphyra polysaccharide-derived carbon dots for non-viral co-delivery of different gene combinations and neuronal differentiation of ectodermal mesenchymal stem cells.

In this study, multifunctional fluorescent carbon dots (CDs) were synthesized using a one-pot hydrothermal carbonization reaction, with the naturally-occurring porphyra polysaccharide (PPS) serving as a single carbon source for the first time and ethylenediamine (Ed) acting as the surface passivation agent. The resulting CDs enjoyed a high quantum yield (56.3%), excitation-dependent fluorescence, small size (<10 nm), spherical shape, uniform distribution, positive surface charge, low cytotoxicity and excellent ability to condense macromolecular plasmid DNA.

A Novel Three-Dimensional Culture System for Oligodendrocyte Precursor Cells.

Oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs). Mechanisms of OPC differentiation have been extensively examined with two-dimensional cell culture systems. However, these cellular events may be more accurately represented using a three-dimensional (3D) model.

Endogenous regeneration: Engineering growth factors for stroke.

Despite the efforts in developing therapeutics for stroke, recombinant tissue plasminogen activator (rtPA) remains the only FDA approved drug for ischemic stroke. Regenerative medicine targeting endogenous growth factors has drawn much interest in the clinical field as it provides potential restoration for the damaged brain tissue without being limited by a narrow therapeutic window. To date, most of the translational studies using regenerative medicines have encountered problems and failures.