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Two-dimensional scaffolds, three-dimensional scaffolds, and dermal substitutes are extensively used for biomedical applications in skin tissue regeneration. Not much explored synthetic polymers, like poly(l-lactic acid)-co-poly-(e-caprolactone) (PLACL), natural polymers, like silk fibroin (SF), and active inducing agents, such as ascorbic acid (AA) and tetracycline hydrochloride (TCH), represent a favorable matrix for fabricating dermal substitutes to engineer artificial skin for wound repair. The profligate nature of residing skin cells near the wound site is a paramount to survival and also regulating stem cells and other cellular networks and mechanical forces. PLACL/SF/TCH/AA nanofibrous scaffolds were fabricated by electrospinning and characterized for fiber morphology, membrane porosity, wettability, and significant subchains using Fourier transform infrared spectroscopy for culturing human-derived dermal fibroblasts. The PLACL, PLACL/SF, PLACL/SF/TCH, and PLACL/SF/TCH/AA scaffolds obtained diameters between 250 and 340 nm. The secretion of collagen by the laboratory-grown fibroblasts over the AA-blended scaffolds was found to be significantly higher compared with that of other scaffolds. The obtained results positively prove that introduction of naturally secreting compounds (AA) by the cells into the nanofibrous scaffolds will favor cell's microenvironment and eventually leads to complete tissue regeneration.

Wound healing is a major problem in diabetic patients and current methods of treatment have met with limited success. Since skin cell renewal is under the control of mesenchymal stem cells (MSCs) treatment of wounds has been attempted with the application of exogenous bone marrow MSCs (hBMMSCs). However, hBMMSCs have the limitations of painful harvest, low cell numbers and short-lived stemness properties unlike MSCs from the Wharton's jelly of human umbilical cords (hWJSCs). Since nanoscaffolds provide three dimensional architectural patterns that mimic in vivo stem cell niches and aloe vera has antibacterial properties we evaluated the use of an aloe vera-polycaprolactone (AV/PCL) nanoscaffold impregnated with green fluorescent protein (GFP)-labeled hWJSCs (GFP-hWJSCs + AV/PCL) or its conditioned medium (hWJSC-CM + AV/PCL) for healing of excisional and diabetic wounds. In skin fibroblast scratch-wound assays exposed to GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL, fibroblasts migrated significantly faster from edges of scratches into vacant areas together with increased secretion of collagen I and III, elastin, fibronectin, superoxide dismutase, and metalloproteinase-1 (MMP-1) compared to controls. After one application of GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL excisional and diabetic wounds in mice showed rapid wound closure, reepithelialization, and increased numbers of sebaceous glands and hair follicles compared to controls. The same wounds exposed to GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL also showed positive keratinocyte markers (cytokeratin, involucrin, filaggrin) and increased expression of ICAM-1, TIMP-1, and VEGF-A compared to controls. AV/PCL nanoscaffolds in combination with hWJSCs appear to have synergistic benefits for wound healing.

Polycaprolactone (PCL), a synthetic biocompatible and biodegradable polymer generally used as a scaffold material for tissue engineering applications. The high stiffness and hydrophobicity of the PCL fiber mesh does not provide significant cell attachment and proliferation in cardiac tissue engineering. Towards this goal, the study focused on a compound of PCL and oligomer hydrogel [Bisphenol A ethoxylated dimethacrylate (BPAEDMA)] processed into electrospun nanofibrous scaffolds. The composition, morphology and mechanical properties of the compound scaffolds, composed of varying ratios of PCL and hydrogel were characterized by scanning electron microscopy, infrared spectroscopy and dynamic mechanical analyzer. The elastic modulus of PCL/BPAEDMA nanofibrous scaffolds was shown to be varying the BPAEDMA weight fraction and was decreased by increasing the BPAEDMA weight fraction. Compound fiber meshes containing 75 wt % BPAEDMA oligomer hydrogel exhibited lower modulus (3.55 MPa) and contact angle of 25(o) . Rabbit cardiac cells cultured for 10 days on these PCL/BPAEDMA compound nanofibrous scaffolds remained viable and expressed cardiac troponin and alpha-actinin proteins for the normal functioning of myocardium. Cell adhesion and proliferations were significantly increased on compound fiber meshes containing 75 wt % BPAEDMA, when compared with other nanofibrous scaffolds. The results observed that the produced PCL/BPAEDMA compound nanofibrous scaffolds promote cell adhesion, proliferation and normal functioning of cardiac cells to clinically beneficial levels, relevant for cardiac tissue engineering.

Heart disease is the leading cause of mortality in many industrialized nations and is often related to irregularities in electrical function that can radically damage cardiac functioning. The aim of this study is to develop a novel therapeutic hybrid scaffold that can couple electrical, mechanical, and biological properties, desirable for cardiac tissue regeneration. BSA/PVA scaffolds are fabricated in the ratio 2:1 and gold nanoparticles (AuNPs) embedded scaffolds in the ratios BSA/PVA/Au of 2:1:0.1 (lower concentration) and BSA/PVA/Au of 2:1:0.4 (higher concentration) by electrospinning. The scaffolds are characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle, Fourier transform infrared (FTIR) spectroscopy, and tensile testing to analyze the fiber morphology, AuNP distribution, hydrophilicity, surface functional groups, and mechanical properties of the scaffolds, respectively. Results show that ex vivo pretreatment of MSCs using 5-aza and AuNPs loaded conductive nanofibrous construct could lead to enhanced cardiomyogenic differentiation and result in superior biological and functional effects on infarcted myocardium regeneration.

Mimicking hybrid extracellular matrix is one of the main challenges for bone tissue engineering (BTE). Biocompatible polycaprolactone/poly(α,β)-DL-aspartic acid/collagen nanofibrous scaffolds were fabricated by electrospinning and nanohydroxyapatite (n-HA) was deposited by calcium phosphate dipping method for BTE. Human mesenchymal stem cells (hMSCs) were cultured on these hybrid scaffolds to investigate the cell proliferation, osteogenic differentiation by alkaline phosphatase activity, mineralization, double immunofluorescent staining using CD90 and expression of osteocalcin. The present study indicated that the PCL/PAA/collagen/n-HA scaffolds promoted greater osteogenic differentiation of hMSCs, proving to be a potential hybrid scaffolds for BTE.

A functional scaffold fabricated is developed from natural polymers, favoring regeneration of the ischemic myocardium. Hemoglobin/gelatin/fibrinogen (Hb/gel/fib) nanofibers are fabricated by electrospinning and are characterized for morphology, scaffold composition, functional groups and hydrophilicity. It is hypothesized that ex vivo pretreatment of mesenchymal stem cells (MSCs) using 5-azacytidine and such a functional nanofibrous construct having a high oxygen-carrying potential could lead to enhanced cardiomyogenic differentiation of MSCs and result in superior biological and functional effects. The combination of a functional nanofibrous scaffold composed of natural polymers and crosslinked with a natural crosslinking agent, phytic acid, and stem cell biology may prove to be a novel therapeutic device for treatment of myocardial infarction.

The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications.

Pioneering research suggests various modes of cellular therapeutics and biomaterial strategies for myocardial tissue engineering. Despite several advantages, such as safety and improved function, the dynamic myocardial microenvironment prevents peripherally or locally administered therapeutic cells from homing and integrating of biomaterial constructs with the infarcted heart. The myocardial microenvironment is highly sensitive due to the nanoscale cues that it exerts to control bioactivities, such as cell migration, proliferation, differentiation, and angiogenesis. Nanoscale control of cardiac function has not been extensively analyzed in the field of myocardial tissue engineering. Inspired by microscopic analysis of the ventricular organization in native tissue, a scalable in-vitro model of nanoscale poly(L-lactic acid)-co -poly(ϵ -caprolactone)/collagen biocomposite scaffold is fabricated, with nanofibers in the order of 594 ± 56 nm to mimic the native myocardial environment for freshly isolated cardiomyocytes from rabbit heart, and the specifically underlying extracellular matrix architecture: this is done to address the specificity of the underlying matrix in overcoming challenges faced by cellular therapeutics. Guided by nanoscale mechanical cues provided by the underlying random nanofibrous scaffold, the tissue constructs display anisotropic rearrangement of cells, characteristic of the native cardiac tissue. Surprisingly, cell morphology, growth, and expression of an interactive healthy cardiac cell population are exquisitely sensitive to differences in the composition of nanoscale scaffolds. It is shown that suitable cell–material interactions on the nanoscale can stipulate organization on the tissue level and yield novel insights into cell therapeutic science, while providing materials for tissue regeneration.

Box Behnken design of experiment was used to study the effect of process variables such as alkali concentration, temperature and time on water retention capacity of the alkaline hydrolysed electrospun fibres. The hydrolysis of electrospun polyacrylonitrile fibres was carried out using sodium hydroxide with different processing conditions like concentration of alkali, temperature and time. With the increase in the concentration of alkali, time and temperature, the water retention capacity of membrane was found to increase in the membranes. Water retention capacities of the membranes were modeled and predicted using empirical as well as artificial neural network (ANN model). The fiber diameter and mean flow pore diameter of electrospun polyacrylonitrile fibers and hydrolyzed fibers shown in SEM images were 310 ± 50, 275 ± 75 nm, 0.9258 and 1.12 microns, respectively. The present study indicated that the nanofibrous membranes have potential for the water absorbing applications. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Bone defects represent a medical and socioeconomic challenge. Engineering bioartificial bone tissues may help to solve problems related to donor site morbidity and size limitations. Nanofibrous scaffolds were electrospun into a blend of synthetic biodegradable polycaprolactone (PCL) with hydroxyapatite (HA) and natural polymer gelatin (Gel) at a ratio of 1:1:2 (PCL/HA/Gel) compared to PCL (9%), PCL/HA (1:1), and PCL/Gel (1:2) nanofibers. These fiber diameters were around 411 ± 158 to 856 ± 157 nm, and the pore size and porosity around 5–35 µm and 76–93%, respectively. The interconnecting porous structure of the nanofibrous scaffolds provides large surface area for cell attachment and sufficient space for nutrient transportation. The tensile property of composite nanofibrous scaffold (PCL/HA/Gel) was highly flexible and allows penetrating osteoblasts inside the scaffolds for bone tissue regeneration. Fourier transform infrared analysis showed that the composite nanofiber contains an amino group, a phosphate group, and carboxyl groups for inducing proliferation and mineralization of osteoblasts for in vitro bone formation. The cell proliferation (88%), alkaline phosphatase activity (77%), and mineralization (66%) of osteoblasts were significantly (P

Novel cost-effective electrospun nanofibrous membrane is established for wound dressing and allogeneic cultured dermal substitute through the cultivation of human dermal fibroblast for skin defects. Synthetic polymers are generally used for tissue engineering and drug delivery applications because of their remarkable mechanical stability and slow degradation. Polycaprolactone (PCL) is used as a bioresorbable polymer in numerous medical devices as well as for tissue engineering applications. The large surface area of the polymer nanofibers with specific modifications facilitates cell adhesion and control of their cellular functions. The objectives of this study was to fabricate electrospun nanofibrous membrane from biodegradable PCL for wound dressing and collagen-blended nanofibrous membrane, and to examine fibroblast attachment, cell proliferation, and morphology of cell matrix interaction. Results of the present investigation prove that the porous nanofibrous membrane is suitable for wound dressing and modified PCL-blended collagen nanofibrous membrane is suitable for the attachment and proliferation of fibroblast, and might have the potential to be applied in tissue engineering as a dermal substitute for the treatment of skin defects and burn wounds.

The objective of this study is to fabricate poly (D,L-lactide-co-glycolide) (PLGA)/Silk fibroin(SF)/Ascorbic acid(AA)/Tetracycline (TC) nanofibrous scaffolds and nanohydroxyapatite (n-HA) was depos...

Hydroxyapatite (HA), the bone mineral and Cissus quadrangularis (CQ), a medicinal plant with osteogenic activity, are attaining increasing interest as a potential therapeutic agent for enhanced bone tissue regeneration. In the present study a synergistic effect of these two agents were analyzed by fabricating PCL-CQ-HA nanofibrous scaffolds by electrospinning and compared with PCL-CQ and PCL (control) nanofibrous scaffolds. Morphology, composition, hydrophilicity, and mechanical properties of the electrospun PCL, PCL-CQ, PCL-CQ-HA nanofibrous scaffolds were examined by Field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), Contact angle and Tensile tests, respectively. The response of human foetal osteoblast cells on these scaffolds were evaluated using MTS assay, alkaline phosphatase activity, alizarin red staining, and osteocalcin expression for bone tissue regeneration. While the observed cellular response to both groups of scaffolds was better than for the control PCL scaffold, the PCL-CQ-HA nanofibrous scaffolds provided the most favorable substrate for cell proliferation and mineralization. The results showed that PCL-CQ-HA nanofibrous scaffolds had appropriate surface roughness for the osteoblast adhesion, proliferation, and mineralization comparing with other scaffolds. The observed investigation of physicochemical and biological properties suggests that the CQ-HA loaded PCL nanofibrous scaffolds serve as a potential biocomposite material for bone tissue engineering. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39835.

Several studies are currently ongoing to construct synthetic bone-like materials with composites of natural and polymeric materials with HA (hydroxyapatite). The present study aims to fabricate composite nanofibrous substrate of Chit/HA (chitosan/HA - 80:25) prepared by dissolving in TFA/DCM (trifluoroacetic acid/dichloromethane) (70:30, w/w) for 5 days and electrospun to fabricate a scaffold for bone tissue engineering. HA (25 wt %) was sonicated for 30 min to obtain a homogenous dispersion of nanoparticles within the Chit (80 wt %) matrix for fabricating composite nanofibrous scaffold (Chit/HA). The nanofibres of Chit and Chit/HA were obtained with fibre diameters of 274 ± 75 and 510 ± 198 nm, respectively, and characterized by FESEM (field emission scanning electron microscopy) and FTIR (Fourier transform infrared). The interaction of hFOBs (human fetal osteoblasts) and nanofibrous substrates were analysed for cell morphology (FESEM), mineralization [ARS (Alizarin Red-S) staining], quantification of minerals and finally identified the elements present in Chit/HA/osteoblasts by EDX (energy-dispersive X-ray) analysis. EDX analysis confirmed that the spherulites contain calcium and phosphorus, the major constituents in calcium phosphate apatite, the mineral phase of the bone. Mineralization was increased significantly (P