A Multimodal Scaffold for SDF1 Delivery Improves Cardiac Function in a Rat Subacute Myocardial Infarct Model

Ischemic heart disease is one of the leading causes of death worldwide. The efficient delivery of therapeutic growth factors could counteract the adverse prognosis of post-myocardial infarction (post-MI). In this study, a collagen hydrogel that is able to load and appropriately deliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physically coupled with a compact collagen membrane in order to provide the suture strength required for surgical implantation. This bilayer collagen-on-collagen scaffold (bCS) showed the suitable physicochemical properties that are needed for efficient implantation, and the scaffold was able to deliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release and a lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integration of the scaffold into the heart after implantation and biocompatibility with the tissue, with a prevalence of anti-inflammatory and pro-angiogenic macrophages, as well as evidence of revascularization and improved cardiac function after 60 days. Moreover, the beneficial effect of the released SDF1 on heart remodeling was confirmed by a significant reduction in cardiac tissue stiffness. Our findings demonstrate that this multimodal scaffold is a desirable matrix that can be used as a drug delivery system and a scaffolding material to promote functional recovery after MI

Complex Coacervate-based Materials for Biomedicine

There has been increasing interest in complex coacervates for deriving and trans- porting biomaterials. Complex coacervates are a dense, polyelectrolyte-rich liq- uid that results from the electrostatic complexation of oppositely charged macroions. Coacervates have long been used as a strategy for encapsulation, par- ticularly in food and personal care products. More recent efforts have focused on the utility of this class of materials for the encapsulation of small molecules, pro- teins, RNA, DNA, and other biomaterials for applications ranging from sensing to biomedicine. Furthermore, coacervate-related materials have found utility in other areas of biomedicine, including cartilage mimics, tissue culture scaffolds, and adhesives for wet, biological environments. Here, we discuss the self- assembly of complex coacervate-based materials, current challenges in the intel- ligent design of these materials, and their utility applications in the broad field of biomedicine

Concise Review: Considerations for the Formulation, Delivery and Administration Routes of Biopharmaceuticals

The drugs of biological origins have attracted the attention of many pharmaceutical companies where it is essential to protect the heterogeneous nature and the optimal three dimensional structures of the different macromolecules. These molecules are used in both the investigation and therapy purposes, so their maximum activities should be maintained. This requires the designing of certain delivery formulations that suits the macromolecule nature, its target organ, the required dose and delivery route, and that’s why the biotech companies invest millions of dollars towards achieving that. The first main focal point of this article includes the recent developments in the formulation technologies for several biomacromolecule classes. The second focal point concentrates on the current considerations for optimizing their delivery for a maximum performance in the body

Model Hemin Derivatives as a New Generation of Iron-based Nitric Oxide Scavengers

Nitric oxide plays multiple pathophysiological roles in breast cancer and regulates the apoptosis and migration of tumour cells according to its gradients. Hence, the modulation of its levels by selective scavenging can effectively treat the fast-growing triple-negative breast cancer (TNBC). Here, we report the modification and full characterization of the hemin (Fe(III)-protoporphyrin IX) structure to minimize the levels of its aggregation and protect against physiological oxidative degradation. The affinity of the final hemin conjugates towards ●NO was studied experimentally and theoretically using quantum mechanics calculations with the further testing of the downstream effects on TNBC cell migration. These compounds represent model hemin derivatives, which showed differential binding to ●NO with different levels of resistance towards the oxidative degradation and aggregation. Moreover, that was accompanied by their efficiency at stopping the ●NO-induced migration of cells, suggesting the promising application of some of them for the further treatment of TNBC

Bioactive composites of hydroxyapatite/polyvinylpyrrolidone for bone regeneration applications

<p>The implantation of bioactive composites for bone repair applications has recently gained the attention of many research groups. The present paper introduces a method for grafting of polyvinylpyrrolidone on the surface of hydroxyapatite (CaHAp) microcrystals by wet precipitation method to manufacture new composite scaffolds with suitability for bone tissue engineering. After grafting with the polymer, the degree of CaHAp crystallinity decreased, and its thermal behavior changed indicating a strong interaction between them. Homogenous clusters of CaHAp particles within the polymeric matrix were observed in combination with an increase in the roughness of the resulting structures. Bioactivity of the composites was tested using MTT assay; a higher viability of the seeded cells was observed relative to those cultured with CaHAp powder.</p

Intercalation of shRNA-plasmid in Mg-Al layered double hydroxide nanoparticles and its cellular internalization for possible treatment of neurodegenerative diseases

In the present work, nanoconjugates of shRNA-plasmid and a non-viral nanoceramic vector, e.g., Mg-Al layered double hydroxide (Mg-Al LDH), were synthesized and intercalated. Subsequently, these particles with an average size of 40-60 nm, were transfected into mammalian neuroblastoma cells (SH-SY5Y). The as prepared Mg-Al LDH was able to protect the incorporated shRNA-plasmid against a range of pH values, DNaseI, endonucleases, and serum components. To test the applicability of the nanoconjugate for future in-vivo studies, serum from three different model experimental animals viz, mouse, rat and guinea pig was used for the serum protection study. Additionally, we showed that prolonged storage at different temperatures does not affect the quality of the nanoconjugate. Using this nanoconjugate to transform cells, a maximum internalization of similar to 26% at 24h was achieved. Lastly, we demonstrated effective and safe delivery of the plasmid by measuring GFP production and shRNA-induced knockdown of TNF alpha

A multimodal scaffold for SDF1 delivery improves cardiac function in a rat subacute myocardial infarct model

Ischemic heart disease is one of the leading causes of death worldwide. The efficient delivery of therapeutic growth factors could counteract the adverse prognosis of post-myocardial infarction (post-MI). In this study, a collagen hydrogel that is able to load and appropriately deliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physically coupled with a compact collagen membrane in order to provide the suture strength required for surgical implantation. This bilayer collagen-on-collagen scaffold (bCS) showed the suitable physicochemical properties that are needed for efficient implantation, and the scaffold was able to deliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release and a lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integration of the scaffold into the heart after implantation and biocompatibility with the tissue, with a prevalence of anti-inflammatory and pro-angiogenic macrophages, as well as evidence of revascularization and improved cardiac function after 60 days. Moreover, the beneficial effect of the released SDF1 on heart remodeling was confirmed by a significant reduction in cardiac tissue stiffness. Our findings demonstrate that this multimodal scaffold is a desirable matrix that can be used as a drug delivery system and a scaffolding material to promote functional recovery after MI