Ameliorating impaired cardiac function in myocardial infarction using exosome-loaded gallic-acid-containing polyurethane scaffolds.

Myocardial infarction (MI) can be tackled by implanting cardiac patches which provide mechanical support to the heart. However, most tissue-engineered scaffolds face difficulty in attenuating oxidative stress, maintaining mechanical stability, and regenerating damaged cardiomyocytes. Here, we fabricated elastic cryogels using polyurethane modified with antioxidant gallic acid in its backbone (PUGA) and further coated them with decellularized extracellular matrix (dECM) to improve adhesiveness, biocompatibility and hemocompatibility. The scaffold was functionalized with exosomes (EXO) isolated from adipose-derived stem cells having regenerative potential. PUGA-dECM + EXO was tested in a rat model with induced MI where echocardiography after 8 weeks of implantation showed significant recovery in treatment group. Histological analysis revealed a decrease in fibrosis after application of patch and promotion of angiogenesis with reduced oxidative stress was shown by immunostaining. Expression of cardiac tissue contractile function marker was also observed in treatment groups. Thus, the proposed biomaterial has a promising application to be utilized as a patch for cardiac regeneration. More detailed studies with larger animal species are needed for using these observations for specific applications.

Experimental diabetic animal models to study diabetes and diabetic complications.

Diabetes is an endocrine illness involving numerous physiological systems. To understand the intricated pathophysiology and disease progression in diabetes, small animals are still the most relevant model systems, despite the availability and progression in numerous invitro and insilico research methods in recent years. In general, experimental diabetes is instigated mainly due to the effectiveness of animal models in illuminating disease etiology. Most diabetes trials are conducted on rodents, while some research is conducted on larger animals. This review will discuss the methodology and mechanisms in detail for preparing diabetic animal models, considering the following important points. The exact pathophysiology of the disease may or may not be replicated in animal models, the correct induction doses must be given and the combination of different approaches for the models is recommended to get desired results.•Animal models are essential to understand diabetes etiology and pathophysiology.•Diabetic models can be developed in both rodents and non-rodents.•Chemically induced and genetic models of diabetes are widely used to study diabetes and diabetic complications.

Periosteum-Mimicking Tissue-Engineered Composite for Treating Periosteum Damage in Critical-Sized Bone Defects.

The periosteum is an indispensable part of the bone that nourishes the cortical bone and acts as a repertoire of osteoprogenitor cells. Periosteal damage as a result of traumatic injuries, infections, or surgical assistance in bone surgeries is often associated with a high incidence of delayed bone healing (union or nonunion) compounded with severe pain and a risk of a secondary fracture. Developing bioengineered functional periosteal substitutes is an indispensable approach to augment bone healing. In this study, we have developed a biomimetic periosteum membrane consisting of electrospun oxygen-releasing antioxidant polyurethane on collagen membrane (polyurethane-ascorbic acid-calcium peroxide containing fibers on collagen (PUAOCC)). Further, to assist bone formation, we have developed a bioactive inorganic-organic composite cryogel (bioglass-collagen-gelatin-nanohydroxyapatite (BCGH)) as a bone substitute. In an in vitro simulated oxidative stress model, PUAOCC supported the primary periosteal cell survival. Moreover, in an in vivo, critical-sized (5.9 mm × 3.2 mm × 1.50 mm) unicortical rat tibial bone defect, implantation of PUAOCC along with the functionalized BCGH led to significant improvement in bone formation along with periosteal regeneration. The periosteal regeneration was confirmed by expression of periosteum-specific periostin and neuronal regulation-related protein markers. Our study demonstrates the development of a periosteum-mimicking membrane with promising applications to facilitate periosteal regeneration, thus assisting bone formation when used in combination with bone composites and mimicking the natural bone repair process.

Transplantation of engineered exosomes derived from bone marrow mesenchymal stromal cells ameliorate diabetic peripheral neuropathy under electrical stimulation.

Diabetic peripheral neuropathy (DPN) is a long-term complication associated with nerve dysfunction and uncontrolled hyperglycemia. In spite of new drug discoveries, development of effective therapy is much needed to cure DPN. Here, we have developed a combinatorial approach to provide biochemical and electrical cues, considered to be important for nerve regeneration. Exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) were fused with polypyrrole nanoparticles (PpyNps) containing liposomes to deliver both the cues in a single delivery vehicle. We developed DPN rat model and injected intramuscularly the fused exosomal system to understand its long-term therapeutic effect. We found that the fused system along with electrical stimulation normalized the nerve conduction velocity (57.60 ± 0.45 m/s) and compound muscle action potential (16.96 ± 0.73 mV) similar to healthy control (58.53 ± 1.10 m/s; 18.19 ± 1.45 mV). Gastrocnemius muscle morphology, muscle mass, and integrity were recovered after treatment. Interestingly, we also observed paracrine effect of delivered exosomes in controlling hyperglycemia and loss in body weight and also showed attenuation of damage to the tissues such as the pancreas, kidney, and liver. This work provides a promising effective treatment and also contribute cutting edge therapeutic approach for the treatment of DPN.