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Background Context: Interbody spinal fusion relies on the use of external fixation and the placement of a fusion cage filled with graft materials (scaffolds) without regard for their mechanical performance. Stability at the fusion site is instead reliant on fixation hardware combined with a selected cage. Ideally, scaffolds placed into the cage should both support the formation of new bone and contribute to the mechanical stability at the fusion site., Purpose: We recently developed a scaffold consisting of silane-modified PCL-TCP (PCL-siTCP) with mechanical properties that can withstand the higher loads generated in the spine. To ensure the scaffold more closely mimicked the bone matrix, we incorporated collagen (Col) and a heparan sulfate glycosaminoglycan sugar (HS3) with increased affinity for heparin-binding proteins such as bone morphogenetic protein-2 (BMP-2). The osteostimulatory characteristic of this novel device delivering exogenous BMP2 was assessed in vitro and in vivo as a prelude to future spinal fusion studies with this device., Study Design/setting: A combination of cell-free assays (BMP2 release), progenitor cell-based assays (BMP2 bioactivity, cell proliferation and differentiation), and rodent ectopic bone formation assays was used to assess the osteostimulatory characteristics of the PCL-siTCP-based scaffolds., Materials and Methods: Freshly prepared rat mesenchymal stem cells were used to determine reparative cell proliferation and differentiation on the PCL-siTCP-based scaffolds over a 28-day period in vitro. The bioactivity of BMP2 released from the scaffolds was assessed on progenitor cells over a 28-day period using ALP activity assays and release kinetics as determined by enzyme-linked immunosorbent assay. For ectopic bone formation, intramuscular placement of scaffolds into Sprague Dawley rats (female, 4 weeks old, 120-150 g) was achieved in five animals, each receiving four treatments randomized for location along the limb. The four groups tested were (1) PCL-siTCP/Col (5-mm diameter×1-mm thickness), PCL-siTCP/Col/BMP2 (5 µg), (3) PCL-siTCP/Col/HS3 (25 µg), and (4) PCL-siTCP/Col/HS3/BMP2 (25 and 5 µg, respectively). Bone formation was evaluated at 8 weeks post implantation by microcomputed tomography (µCT) and histology., Results: Progenitor cell-based assays (proliferation, mRNA transcripts, and ALP activity) confirmed that BMP2 released from PCL-siTCP/Col/HS3 scaffolds increased ALP expression and mRNA levels of the osteogenic biomarkers Runx2, Col1a2, ALP, and bone gla protein-osteocalcin compared with devices without HS3. When the PCL-siTCP/Col/HS3/BMP2 scaffolds were implanted into rat hamstring muscle, increased bone formation (as determined by two-dimensional and three-dimensional µCTs and histologic analyses) was observed compared with scaffolds lacking BMP2. More consistent increases in the amount of ectopic bone were observed for the PCL-siTCP/Col/HS3/BMP2 implants compared with PCL-siTCP/Col/BMP2. Also, increased mineralizing tissue within the pores of the scaffold was seen with modified-tetrachrome histology, a result confirmed by µCT, and a modest but detectable increase in both the number and the thickness of ectopic bone structures were observed with the PCL-siTCP/Col/HS3/BMP2 implants., Conclusions: The combination of PCL-siTCP/Col/HS3/BMP2 thus represents a promising avenue for further development as a bone graft alternative for spinal fusion surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The Wharton's Jelly (WJ) is an established source of mesenchymal stem cells (MSC). We compared 3 methods of extracting WJ-MSC from cryopreserved tissue and determined that enzymatic digestion of the WJ yielded the most viable MSC, compared to the explant and mechanical digestion methods. The enzymatically-released WJ-MSC conformed to the International Society for Cellular Therapy (ISCT) criteria: displayed plastic-adherence, co-expressed CD73, CD90, CD105 and were negative for hematopoietic lineage cell markers.

In the present study, polycaprolactone-tricalcium phosphate (PCL/TCP) scaffolds with two different fibre laydown patterns, which were coated with hydroxyapatite and gelatine, were used as an approach for optimizing bone regeneration in a critical-sized calvarial defect. After 12 weeks, bone regeneration was quantified using microcomputed tomography (micro-CT) analysis, biomechanical testing, and histological evaluation. Notably, the experimental groups with coated scaffolds showed lower bone formation and lower biomechanical properties within the defect compared to the uncoated scaffolds. Surprisingly, the different laydown pattern of the fibres resulted in different bone formation and biomechanical properties: the 0°/60°/120° scaffolds revealed lower bone formation and biomechanical properties compared to the 0°/90° scaffolds in all the experimental groups. Therefore, future bone regeneration strategies utilizing scaffolds should consider scaffold architecture as an important factor during the scaffold optimization stages in order to move closer to a clinical application., (Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

A significant stumbling block in the creation of functional three-dimensional (3D) engineered tissues is the proper vascularization of the constructs. Furthermore, in the context of electrospinning, the development of 3D constructs using this technique has been hindered by the limited infiltration of cells into their structure. In an attempt to address these issues, a hybrid mesh of poly (ɛ-caprolactone)-collagen blend (PCL/Col) and hyaluronic acid (HA) hydrogel, Heprasil™ was created via a dual electrodeposition system. Simultaneous deposition of HA and PCL/Col allowed the dual loading and controlled release of two potent angiogenic growth factors VEGF(165) and PDGF-BB over a period of five weeks in vitro. Furthermore, this manner of loading sustained the bioactivity of the two growth factors. Utilizing an in-house developed 3D co-culture assay model of human umbilical vein endothelial cells and lung fibroblasts, the growth factor-loaded hybrid meshes was shown to not only support cellular attachment, but also their infiltration and the recapitulation of primitive capillary network in the scaffold's architecture. Thus, the creation of a PCL/Col-Heprasil hybrid scaffold is a step forward toward the attainment of a 3D bio-functionalized, vascularized tissue engineering construct., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The objective of this present study was to improve the functional performance of rapid prototyped scaffolds for bone tissue engineering through biomimetic composite coating. Rapid prototyped poly(ε-caprolactone)/tri-calcium phosphate (PCL/TCP) scaffolds were fabricated using the screw extrusion system (SES). The fabricated PCL/TCP scaffolds were coated with a carbonated hydroxyapatite (CHA)-gelatin composite via biomimetic co-precipitation. The structure of the prepared CHA-gelatin composite coating was studied by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Compressive mechanical testing revealed that the coating process did not have any detrimental effect on the mechanical properties of the scaffolds. The cell-scaffold interaction was studied by culturing porcine bone marrow stromal cells (BMSCs) on the scaffolds and assessing the proliferation and bone-related gene and protein expression capabilities of the cells. Confocal laser microscopy and SEM images of the cell-scaffold constructs showed a uniformly distributed cell sheet and accumulation of extracellular matrix in the interior of CHA-gelatin composite-coated PCL/TCP scaffolds. The proliferation rate of BMSCs on CHA-gelatin composite-coated PCL/TCP scaffolds was about 2.3 and 1.7 times higher than that on PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds, respectively, by day 10. Furthermore, reverse transcription polymerase chain reaction and Western blot analysis revealed that CHA-gelatin composite-coated PCL/TCP scaffolds stimulate osteogenic differentiation of BMSCs the most, compared with PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds. These results demonstrate that CHA-gelatin composite-coated rapid prototyped PCL/TCP scaffolds are promising for bone tissue engineering., (Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Numerous challenges remain in the successful clinical translation of cell-based therapies for musculoskeletal tissue repair, including the identification of an appropriate cell source and a viable cell delivery system. The aim of this study was to investigate the attachment, colonization, and osteogenic differentiation of two stem cell types, human mesenchymal stem cells (hMSCs) and human amniotic fluid stem (hAFS) cells, on electrospun nanofiber meshes. We demonstrate that nanofiber meshes are able to support these cell functions robustly, with both cell types demonstrating strong osteogenic potential. Differences in the kinetics of osteogenic differentiation were observed between hMSCs and hAFS cells, with the hAFS cells displaying a delayed alkaline phosphatase peak, but elevated mineral deposition, compared to hMSCs. We also compared the cell behavior on nanofiber meshes to that on tissue culture plastic, and observed that there is delayed initial attachment and proliferation on meshes, but enhanced mineralization at a later time point. Finally, cell-seeded nanofiber meshes were found to be effective in colonizing three-dimensional scaffolds in an in vitro system. This study provides support for the use of the nanofiber mesh as a model surface for cell culture in vitro, and a cell delivery vehicle for the repair of bone defects in vivo.

Conventional clinical therapies are unable to resolve osteochondral defects adequately; hence, tissue engineering solutions are sought to address the challenge. A biphasic implant that was seeded with mesenchymal stem cells (MSCs) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a polycaprolactone (PCL) cartilage scaffold and a PCL-tricalcium phosphate osseous matrix. Autologous MSCs were seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL-collagen electrospun mesh, which served as a substitute for periosteal flap in preventing cell leakage. Controls without either implanted MSCs or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by superior glycosaminoglycan maintenance. This positive morphological outcome was supported by a higher relative Young's modulus, which indicated functional cartilage restoration. Bone ingrowth and remodeling occurred in all groups, with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover, healing was inferior at the patellar groove when compared with the medial condyle and this was attributed to the native biomechanical features.

In this study, poly (epsilon-caprolactone) [PCL] and its collagen composite blend (PCL/Col) were fabricated to scaffolds using electrospinning method. Incorporated collagen was present on the surface of the fibers, and it modulated the attachment and proliferation of pig bone marrow mesenchymal cells (pBMMCs). Osteogenic differentiation markers were more pronounced when these cells were cultured on PCL/Col fibrous meshes, as determined by immunohistochemistry for collagen type I, osteopontin, and osteocalcin. Matrix mineralization was observed only on osteogenically induced PCL/Col constructs. Long bone analogs were created by wrapping osteogenic cell sheets around the PCL/Col meshes to form hollow cylindrical cell-scaffold constructs. Culturing these constructs under dynamic conditions enhanced bone-like tissue formation and mechanical strength. We conclude that electrospun PCL/Col mesh is a promising material for bone engineering applications. Its combination with osteogenic cell sheets offers a novel and promising strategy for engineering of tubular bone analogs.

A common problem in the design of tissue engineered scaffolds using electrospun scaffolds is the poor cellular infiltration into the structure. To tackle this issue, three approaches to scaffold design using electrospinning were investigated: selective leaching of a water-soluble fiber phase (poly ethylene oxide (PEO) or gelatin), the use of micron-sized fibers as the scaffold, and a combination of micron-sized fibers with codeposition of a hyaluronic acid-derivative hydrogel, Heprasil. These designs were achieved by modifying a conventional electrospinning system with two charged capillaries and a rotating mandrel collector. Three types of scaffolds were fabricated: medical grade poly(epsilon-caprolactone)/collagen (mPCL/Col) cospun with PEO or gelatin, mPCL/Col meshes with micron-sized fibers, and mPCL/Col microfibers cosprayed with Heprasil. All three scaffold types supported attachment and proliferation of human fetal osteoblasts. However, selective leaching only marginally improved cellular infiltration when compared to meshes obtained by conventional electrospinning. Better cell penetration was seen in mPCL/Col microfibers, and this effect was more pronounced when Heprasil regions were present in the structure. Thus, such techniques could be further exploited for the design of cell permeable fibrous meshes for tissue engineering applications.

Scaffolds manufactured from biological materials promise better clinical functionality, providing that characteristic features are preserved. Collagen, a prominent biopolymer, is used extensively for tissue engineering applications, because its signature biological and physico-chemical properties are retained in in vitro preparations. We show here for the first time that the very properties that have established collagen as the leading natural biomaterial are lost when it is electro-spun into nano-fibres out of fluoroalcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol or 2,2,2-trifluoroethanol. We further identify the use of fluoroalcohols as the major culprit in the process. The resultant nano-scaffolds lack the unique ultra-structural axial periodicity that confirms quarter-staggered supramolecular assemblies and the capacity to generate second harmonic signals, representing the typical crystalline triple-helical structure. They were also characterised by low denaturation temperatures, similar to those obtained from gelatin preparations (p>0.05). Likewise, circular dichroism spectra revealed extensive denaturation of the electro-spun collagen. Using pepsin digestion in combination with quantitative SDS-PAGE, we corroborate great losses of up to 99% of triple-helical collagen. In conclusion, electro-spinning of collagen out of fluoroalcohols effectively denatures this biopolymer, and thus appears to defeat its purpose, namely to create biomimetic scaffolds emulating the collagen structure and function of the extracellular matrix.

In this study, a nanofiber mesh made by co-electrospinning medical grade poly(epsilon-caprolactone) and collagen (mPCL/Col) was fabricated and studied. Its mechanical properties and characteristics were analyzed and compared to mPCL meshes. mPCL/Col meshes showed a reduction in strength but an increase in ductility when compared to PCL meshes. In vitro assays revealed that mPCL/Col supported the attachment and proliferation of smooth muscle cells on both sides of the mesh. In vivo studies in the corpus cavernosa of rabbits revealed that the mPCL/Col scaffold used in conjunction with autologous smooth muscle cells resulted in better integration with host tissue when compared to cell free scaffolds. On a cellular level preseeded scaffolds showed a minimized foreign body reaction.

Current clinical therapies for traumatic or chronic injuries involving osteochondral tissue result in temporary pain reduction and filling of the defect but with biomechanically inferior repair tissue. Tissue engineering of osteochondral repair tissue using autologous cells and bioactive biomaterials has the potential to overcome the current limitations and results in native-like repair tissue with good integration capabilities. For this reason, we applied two modem biomaterial design techniques, namely, electrospinning and fused deposition modeling (FDM), to produce bioactive poly(epsilon-caprolactone)/collagen (PCL/Col) type I and type II-PCL-tri-calcium phosphate (TCP)/Col composites for precursor cell-based osteochondral repair. The application of these two design techniques (electrospinning and FDM) allowed us to specifically produce the a suitable three-dimensional (3D) environment for the cells to grow into a particular tissue (cartilage and bone) in vitro prior to in vivo implantation. We hypothesize that our new designed biomaterials, seeded with autologous bone marrow-derived precursor cells, in combination with bioreactor-stimulated cell-culture techniques can be used to produce clinically relevant osteochondral repair tissue.

Analogous of pixels to two-dimensional pictures, voxels—in the form of either small cubes or spheres—are the basic building blocks of three-dimensional objects. However, precise manipulation of viscoelastic bio-ink voxels in three-dimensional space represents a grand challenge in both soft matter science and biomanufacturing. Here, we present a voxelated bioprinting technology that enables the digital assembly of interpenetrating double-network hydrogel droplets made of polyacrylamide/alginate-based or hyaluronic acid/alginate-based polymers. The hydrogels are crosslinked via additive-free and biofriendly click reaction between a pair of stoichiometrically matched polymers carrying norbornene and tetrazine groups, respectively. We develop theoretical frameworks to describe the crosslinking kinetics and stiffness of the hydrogels, and construct a diagram-of-state to delineate their mechanical properties. Multi-channel print nozzles are developed to allow on-demand mixing of highly viscoelastic bio-inks without significantly impairing cell viability. Further, we showcase the distinctive capability of voxelated bioprinting by creating highly complex three-dimensional structures such as a hollow sphere composed of interconnected yet distinguishable hydrogel particles. Finally, we validate the cytocompatibility and in vivo stability of the printed double-network scaffolds through cell encapsulation and animal transplantation. Voxel bioprinting uses bio-ink droplets as building blocks to create functional tissue mimics, but manipulating small bio-ink droplets in 3D space can be challenging. Here, the authors report a bioprinting technology allowing prescribed assembly of bio-ink voxels to form robust 3D constructs. [ABSTRACT FROM AUTHOR]

In tissue engineering (TE) and regenerative medicine, the accessibility of engineered scaffolds that modulate inflammatory states is extremely necessary. The aim of the current work was to assess the efficacy of metformin (MET) incorporated in PLGA/Collagen nanofibers (Met-PLGA/Col NFs) to modulate RAW264.7 macrophage phenotype from pro-inflammatory status (M1) to anti-inflammatory status (M2). Given this, MET-PLGA/Col NFs were fabricated using an electrospinning technique. Structural characterization such as morphology, chemical and mechanical properties, and drug discharge pattern were assessed. MTT assay test exposed that MET-PLGA/Col NFs remarkably had increased cell survival in comparison with pure PLGA/Collagen NFs and control (p < 0.05) 72 h after incubation. Based on the qPCR assay, a reduction in the expression of iNOS-2 and SOCS3 was found in the cells seeded on MET-PLGA/Col NFs, demonstrating the substantial modulation of the M1 phenotype to the M2 phenotype. Moreover, it was determined a main decrease in the pro-inflammatory cytokines and mediator's expression but the growth factors amount related to anti-inflammatory M2 were meaningfully upregulated. Finally, MET-PLGA/Col NFs possibly will ensure a beneficial potential for effective variation of the macrophage response from an inflammatory phase (M1) to a pro-regenerative (M2) phase. [ABSTRACT FROM AUTHOR]

Even with its simplicity, ease of use, and wide variety of applications, the ELS technique has gained in popularity. The characteristics of EFs fibres (FBs) can be affected by changing process variables or polymeric solution (PLs) conditions. Many of the elements that impact ELS, however, are linked. An ideal ELS method keeps these parameters constant and consistently creates NFs with consistent physicochemical properties. The PLs might be aqueous, polymeric melt, or emulsion, resulting in NF production in various forms. Inverting the polarity and altering the collector design can also change the NF characteristics. Blending, surface functionalization, and emulsion generation are all methods for incorporating the active moiety into polymeric FBs. The multilayer polymer covering permits the incorporated active moiety to be released constantly, and the NFs may be modified to carry a variety of medications. Polymer (PLY)-derived EFs and NFs are utilized for DD, ANC, WH, BS, SiRNA delivery, stem cell treatment, and growth factors. This review compiles papers concerning the utilization of EFs and NFs in biomedical applications (BMA). [ABSTRACT FROM AUTHOR]

The aim of this study is to correlate the solubility and electrospinnability of gelatin in different organic solvent systems. Teas graph was employed using the Hansen parameters in this systematic study to map the solvents that dissolve and enable the electrospinning of gelatin. It was found that in some cases, the solvent dissolved gelatin but the solution was not spinnable. Increasing the hydrogen bonding force (fh) assisted in the electrospinning of the gelatin solution. Higher dispersion force (fd) improves the electrospinnability at lower concentration of gelatin. The viscosity of the solution of pure acetic acid (AA) is higher than the binary solution of 3:1 AA/water and 3:1 AA/tetrahydrofuran (THF) for the same concentration of gelatin; the higher viscosity enhanced the electrospinning properties. Interestingly, field-emission scanning electron microscopy arrayed that the effect of increasing the concentration of gelatin in the pure AA system resulted in the formation of thicker fibres, however, it induced the formation of uniform fibres in the 3:1 AA/water system, whereas beaded morphology was obtained when lower concentration of gelatin was used. The fibres obtained from electrospinning the solution of 3:1 AA/THF resulted in the formation of thicker and non-uniform fibres due to the low electrical conductivity as well as the high volatility of the solution. Attenuated total reflectance-Fourier transform infrared spectroscopy portrayed all the major peaks of gelatin in the electrospun fibres. However, widening of the Amide-A peak of gelatin was observed when the solvent system of formic acid and 3:1 AA/THF were used. Thermal study of the fibre mats depicts that the binary solvent system using AA is more suitable to obtain nanofibres with more analogous structure to pristine gelatin. The electrospun samples of gelatin in the different solvent systems did not exhibit any cytotoxity on the HeLa cell line. Teas graph can be used as a quick solvent selection tool to prepare electrospinning solutions of gelatin blended with synthetic polymers to obtain nanofibres for biomedical applications. [ABSTRACT FROM AUTHOR]

Since the second half of the 20th century, bioceramics are widely used as a substitute for hard tissue engineering. Bioceramics including zirconia, alumina, hydroxyapatite, and bioactive glass plays a vital role in the design of tissue engineering scaffolds with tailor-made properties. The bioceramics scaffold has been used to replace or regenerate the tissue of the human body due to its excellent mechanical strength, biocompatibility, chemical stability, corrosion restriction behavior, and wear resistance. The advancement in technology has made the form of bioceramics and their function, structure, and composition more diversified, and manifold. Considering the promising role of the use of bioceramics in tissue engineering, we proposed this review, presenting the classification of bioceramics, their physiochemical properties, degradation pathway, product development so far, and their application in tissue engineering. The calcium phosphate and bioglass-based composite scaffold have also been discussed in detail. Furthermore, this paper also discussed the toxicity evaluation and market perspective of bioceramics. Thus, this review gives a complete insight into bioceramics for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Thermogelling hydrogels based on poly(N‐isopropyl acrylamide) (p[NiPAAm]) and crosslinked with a peptide‐bearing macromer poly(glycolic acid)‐poly(ethylene glycol)‐poly(glycolic acid)‐di(but‐2‐yne‐1,4‐dithiol) (PdBT) were fabricated to assess the role of hydrogel charge and lower critical solution temperature (LCST) over time in influencing cellular infiltration and tissue integration in an ex vivo cartilage explant model over 21 days. The p(NiPAAm)‐based thermogelling polymer was synthesized to possess 0, 5, and 10 mol% dimethyl‐γ‐butyrolactone acrylate (DBA) to raise the LCST over time as the lactone rings hydrolyzed. Further, three peptides were designed to impart charge into the hydrogels via conjugation to the PdBT crosslinker. The positively, neutrally, and negatively charged peptides K4 (+), zwitterionic K2E2 (0), and E4 (−), respectively, were conjugated to the modular PdBT crosslinker and the hydrogels were evaluated for their thermogelation behavior in vitro before injection into the cartilage explant models. Samples were collected at days 0 and 21, and tissue integration and cellular infiltration were assessed via mechanical pushout testing and histology. Negatively charged hydrogels whose LCST changed over time (10 mol% DBA) were demonstrated to promote the greatest tissue integration when compared to the positive and neutral gels of the same thermogelling polymer formulation due to increased transport and diffusion across the hydrogel‐tissue interface. Indeed, the negatively charged thermogelling polymer groups containing 5 and 10 mol% DBA demonstrated cellular infiltration and cartilage‐like matrix deposition via histology. This study demonstrates the important role that material physicochemical properties play in dictating cell and tissue behavior and can inform future cartilage tissue engineering strategies. [ABSTRACT FROM AUTHOR]

In order to create a perfect bone scaffold, nanocomposites are the best options, as they can be engineered to have the composition, structure and properties of natural bone. In the present study, the layer-by-layer and hybrid nanofiber scaffold are fabricated by electrospinning method using a combination of PCL/PVP and PVA/β-TCP layers. We study and compare the morphological properties (scanning electron microscope (SEM), swelling ratio and porosity), mechanical properties (tensile strength, elongation at break and tensile modulus) and biodegradability of the scaffolds. The average fiber diameter measured for layer-by-layer and hybrid scaffolds is 446 ± 128 nm and 505 ± 261 nm, respectively. The tensile strength for the layer-by-layer and hybrid scaffolds is 7.40 ± 3.40 MPa and 6.57 ± 1.64 MPa, respectively, and the degradation rate for layer-by-layer and hybrid scaffolds is 26 ± 2% and 40 ± 5%, respectively. So the results show the desired mechanical properties and compatibility of scaffolds. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay shows cell viability above 80% and absence of cell cytotoxicity for layer-by-layer and hybrid scaffolds after 3, 5 and 7 days of rat marrow stromal cell (rMSC) culture. The morphology and proliferation of rMSC cells show the suitability of the scaffolds for tissue engineering application. Therefore, both types of scaffolds can be used in several tissue engineering applications, including improvement of bone tissue regeneration. [ABSTRACT FROM AUTHOR]

Segmental bone defects caused by trauma, tumor resection or congenital malformations are often reconstructed with autologous, allogeneic bone grafts or artificial bone materials, of which, about 5% ~ 10% will have delayed healing or even nonunion of fractures. The loss of periosteum and excessive accumulation of ROS in fracture site leads to the aging of osteoblasts and the decline of their proliferation and differentiation, thus affecting the fracture healing process. In this study, we prepared a functional modified artificial periosteum β-TCP/MnO 2 /PCL(β-TMP) by electrospinning with a function of catalyzing decomposition of H 2 O 2 . We examined the surface morphology of β-TMP, the concentration of Ca, P and Mn of β-TMP, as well as the diameter distribution range of nanofibers on β-TMP. Through X-ray diffraction patterns and Fourier transform infrared spectra, β-TMP was characterized and its hydrophilicity was tested. The release of Mn 2+ and Ca 2+ of 0.1 and 0.05% β-TMP in different pH values (7.4 and 5.5) determined by ICP. We also identified that β-TMP could reduce the level of ROS in cells by lowering the level of H 2 O 2 . 0%, 0.05% and 0.1% β-TMP displayed good cell compatibility, cell adhesion and cellular morphology in the condition with or without H 2 O 2 . 0.5% β-TMP showed compromised cell compatibility in normal condition, however, the compromised phenotypes could be partially rescued in the present of H 2 O 2 . Compared with 0%, 0.05% and 0.1% β-TMP displayed higher osteoblastic differentiation with or without H 2 O 2 in BMSCs as well as in MG-63. In sum, β-TMP helped osteogenesis and promoted repair of bone defects., (© 2023 Wiley Periodicals LLC.)

In this work, composite electrospun fibers containing innovative bioactive glass nanoparticles were produced and characterized. Poly(ε-caprolactone), benign solvents, and sol-gel B- and Cu-doped bioactive glass powders were used to fabricate fibrous scaffolds. The retention of bioactive glass nanoparticles in the polymer matrix, the electrospinnability of this novel solution and the obtained electrospun composites were extensively characterized. As a result, composite electrospun fibers characterized by biocompatibility, bioactivity, and exhibiting overall properties adequate for both hard and soft tissue engineering applications, have been produced. The addition of these bioactive glass nanoparticles was, indeed, able to impart bioactive properties to the fibers. Cell culture studies show promising results, demonstrating proliferation and growth of cells on the composite fibers. Wettability, degradation rate, and mechanical performance were also tested and are in line with previous results., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Articular cartilage was expected to be one of the first tissues to be successfully engineered, but replicating the complex fibril architecture and the cellular distribution of the native cartilage has proven difficult. While electrospinning has been widely used to reproduce the depth-dependent fibre architecture in 3D scaffolds, the chondrocyte-controlled distribution remains an unsolved problem. To incorporate cells homogeneously through the depth of scaffolds, a combination of polymer electrospinning and cell seeding is necessary. A multi-layer approach alternating between polymer electrospinning with chondrocyte electrospraying can be a solution. Still, the success of this process is related to the survival rate of the electrosprayed chondrocytes embedded within the electrospun mesh. In this regard, the present study investigated the impact of the multi-layered process and the supplementation of the electrospray chondrocyte suspension with different concentrations of Gelatin and Alginate on the viability of electrosprayed chondrocytes embedded within a Polycaprolactone/Gelatin electrospun mesh and on the mechanical properties of the resulting meshes. The addition of Gelatin in the chondrocyte suspension did not increase significantly (p > 0.05) the percentage of viable electrosprayed chondrocytes (25%), while 3 wt% Alginate addition led to a significant (p < 0.05) increase in chondrocyte viability (50%) relative to the case without polymer supplement (15%). Furthermore, the addition of both polymer supplements increased the mechanical properties of the multi-layer construct. These findings imply that this multi-layered approach can be applied to cartilage TE allowing for automated chondrocyte integration during scaffolds creation. [ABSTRACT FROM AUTHOR]

Pepsin-soluble collagen (PSC) from the skin of Nile tilapia (Oreochromis niloticus) was used for the obtention of collagen scaffolds, and their structural and physico-chemical properties were described. The PSC extraction yield was 18.3%, and the type I collagen was identified from it; the PSC scaffolds were successfully elaborated by electrospinning. The Fourier transform infrared spectrum confirmed that the triple helix structure was maintained before and after the electrospinning process. The differential scanning calorimetry analysis revealed high PSC temperature denaturation (38°C) and PSC scaffolds (30°C). These findings show that PSC can be an effective source of collagen for the PSC scaffold obtention and be further used as a potential biomaterial. [ABSTRACT FROM AUTHOR]

Electrospun fibers have received significant interests for various application areas such as filtration, composites and biomedical products due to their large surface area, good continuity, high porosity and many other unique properties. In bio-related applications, electrospun fibers have been used for in-situ drug delivery, tissue engineering scaffolds and wound dressing. In more recent years, there has been a drive toward novel electrospun fibers with added functionalities. Nanoengineering of electrospun fibers has introduced many of such novel properties. Through this review, researchers are provided with a state of the art overview of nanoenhanced electrospun fibers with added functionalities. Examples of some nanoengineered fibers include; surface functionalization, multi-component fibers, porous nanofibers, the creation of surface nano-topographies, and the incorporation of nanoparticles to create hierarchical fibrous structures for tailoring of physicochemical properties with a special focus on biomedical applications. [ABSTRACT FROM AUTHOR]

Large bone defects remain a clinical challenge because they do not heal spontaneously. 3-D printed scaffolds are a promising treatment option for such critical defects. Recent scaffold design strategies have made use of computer modelling techniques to optimize scaffold design. In particular, scaffold geometries have been optimized to avoid mechanical failure and recently also to provide a distinct mechanical stimulation to cells within the scaffold pores. This way, mechanical strain levels are optimized to favour the bone tissue formation. However, bone regeneration is a highly dynamic process where the mechanical conditions immediately after surgery might not ensure optimal regeneration throughout healing. Here, we investigated in silico whether scaffolds presenting optimal mechanical conditions for bone regeneration immediately after surgery also present an optimal design for the full regeneration process. A computer framework, combining an automatic parametric scaffold design generation with a mechano-biological bone regeneration model, was developed to predict the level of regenerated bone volume for a large range of scaffold designs and to compare it with the scaffold pore volume fraction under favourable mechanical stimuli immediately after surgery. We found that many scaffold designs could be considered as highly beneficial for bone healing immediately after surgery; however, most of them did not show optimal bone formation in later regenerative phases. This study allowed to gain a more thorough understanding of the effect of scaffold geometry changes on bone regeneration and how to maximize regenerated bone volume in the long term. [ABSTRACT FROM AUTHOR]

Tubular polymer scaffolds based on tissue engineering techniques have been studied as potential alternatives for vascular regeneration implants. The blood vessels of the cardiovascular system are mainly fibrous, composed of collagen (Col) and elastin (El), and its inner layer consists of endothelial cells. In this work, Col and El were combined with polyurethane (PU), a biocompatible synthetic polymer, and rotary jet spinning, a new and highly productive technique, to produce fibrous scaffolds. The scaffolds produced at 18 000 rpm presented homogeneous, bead‐free, and solvent‐free fibers. The blend formation between PU‐Col‐El was identified by chemical composition analysis and enhanced the thermal stability up to 324°C. The hydrophilic nature of the scaffold was revealed by its low contact angle. Cell viability of human umbilical vein endothelial cells with the scaffold was proven for 72 hours. The combined strategy of rotary jet spinning with a polymer blend containing Col and El was verified as an effective and promising alternative to obtain tubular scaffolds for tissue engineering on a large‐scale production. [ABSTRACT FROM AUTHOR]

Skin injuries and in particular, chronic wounds, are one of the major prevalent medical problems, worldwide. Due to the pivotal role of angiogenesis in tissue regeneration, impaired angiogenesis can cause several complications during the wound healing process and skin regeneration. Therefore, induction or promotion of angiogenesis can be considered as a promising approach to accelerate wound healing. This article presents a comprehensive overview of current and emerging angiogenesis induction methods applied in several studies for skin regeneration, which are classified into the cell, growth factor, scaffold, and biological/chemical compound‐based strategies. In addition, the advantages and disadvantages of these angiogenic strategies along with related research examples are discussed in order to demonstrate their potential in the treatment of wounds. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA) and biphasic hydroxyapatite/beta‐tricalcium phosphate (biphasic HA/β‐TCP) were synthesized using thermal sintering. The parameters‐ sintering temperature (600°C, 900°C, and 1200°C), biological source used (fish bone, egg shells, and fish scales), and soaking time (2, 6, and 10 hours) were permuted to study their effects on the properties of the resultant apatite. Morphological study revealed that the smallest (60 nm) spherical particle and the largest (470 nm) irregular shaped particle were obtained from the fish bone sample sintered at 600°C and at 1200°C respectively. FTIR and XRD results showed that as the sintering temperature is increased, the phase transformation from HA to β‐TCP takes place. Only the final products from fishbone sample at 600°C are pure carbonated HA. The crystallinity of synthesized particles ranged from 79% to 98%. Soaking time has no effect on phase composition of the apatite but has significant effect on crystallite size; increase in soaking time increases crystallite size and particle shape becomes more spherical. Interestingly, the fish bone sample sintered at 900°C has higher crystallinity and crystallite size compared to the fish scale sample sintered at the same temperature. EDX confirmed that non‐stoichiometric apatite with Ca/P ratio ranging from 1.47 to 1.91 can be obtained by varying the sintering conditions. The antibacterial test revealed that both calcium apatite obtained from fish bones and fish scales have inhibited bacterial growth; apatite from fish bone works faster than fish scales. The in vitro cytotoxicity test ensured that all the calcium apatite except for eggshell are non‐cytotoxic. Thus, apatite with excellent microbial activity can be obtained by using fish wastes, and by tuning the sintering parameters, the apatite with desired types and properties can be synthesized for different biomedical applications. [ABSTRACT FROM AUTHOR]

Inconsistent therapeutic efficacy of mesenchymal stem cells (MSCs) in regenerative medicine has been documented in many clinical trials. Precise prediction on the therapeutic outcome of a MSC therapy based on the patient's conditions would provide valuable references for clinicians to decide the treatment strategies. In this article, we performed a meta-analysis on MSC therapies for cartilage repair using machine learning. A small database was generated from published in vivo and clinical studies. The unique features of our neural network model in handling missing data and calculating prediction uncertainty enabled precise prediction of post-treatment cartilage repair scores with coefficient of determination of 0.637 ± 0.005. From this model, we identified defect area percentage, defect depth percentage, implantation cell number, body weight, tissue source, and the type of cartilage damage as critical properties that significant impact cartilage repair. A dosage of 17 − 25 million MSCs was found to achieve optimal cartilage repair. Further, critical thresholds at 6% and 64% of cartilage damage in area, and 22% and 56% in depth were predicted to significantly compromise on the efficacy of MSC therapy. This study, for the first time, demonstrated machine learning of patient-specific cartilage repair post MSC therapy. This approach can be applied to identify and investigate more critical properties involved in MSC-induced cartilage repair, and adapted for other clinical indications. Author summary: Cartilage damage affects the life quality of hundreds of millions of people, causing chronic joint pain and disability. Cartilage has poor regenerative capacity. Only minor damage could improve on its own or with passive treatments, while more severe damage often requires surgery. In recent decades, stem cell therapy has become a promising treatment option to reduce pain and repair cartilage. However, with complex mechanisms and various factors involved, efficient and consistent cartilage regeneration remains elusive. Our neural network learns information from clinical trials and animal studies to predict therapeutic outcomes along with the confidence level based on the patient's condition. This machine learning approach provides an important reference and significant insights into the optimization of treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Current design strategies for small diameter vascular grafts (< 6 mm internal diameter; ID) are focused on mimicking native vascular tissue because the commercially available grafts still fail at small diameters, notably due to development of intimal hyperplasia and thrombosis. To overcome these challenges, various design approaches, material selection, and surface modification strategies have been employed to improve the patency of small-diameter grafts. Review: The purpose of this review is to outline various considerations in the development of small-diameter vascular grafts, including material choice, surface modifications to enhance biocompatibility/endothelialization, and mechanical properties of the graft, that are currently being implanted. Additionally, we have taken into account the general vascular physiology, tissue engineering approaches, and collective achievements of the authors in this area. We reviewed both commercially available synthetic grafts (e-PTFE and PET), elastic polymers such as polyurethane and biodegradable and bioresorbable materials. We included naturally occurring materials by focusing on their potential application in the development of future vascular alternatives. Conclusion: Until now, there are few comprehensive reviews regarding considerations in the design of small-diameter vascular grafts in the literature. Here-in, we have discussed in-depth the various strategies employed to generate engineered vascular graft due to their high demand for vascular surgeries. While some TEVG design strategies have shown greater potential in contrast to autologous or synthetic ePTFE conduits, many are still hindered by high production cost which prevents their widespread adoption. Nonetheless, as tissue engineers continue to develop on their strategies and procedures for improved TEVGs, soon, a reliable engineered graft will be available in the market. Hence, we anticipate a viable TEVG with resorbable property, fabricated via electrospinning approach to hold a greater potential that can overcome the challenges observed in both autologous and allogenic grafts. This is because they can be mechanically tuned, incorporated/surface-functionalized with bioactive molecules and mass-manufactured in a reproducible manner. It is also found that most of the success in engineered vascular graft approaching commercialization is for large vessels rather than small-diameter grafts used as cardiovascular bypass grafts. Consequently, the field of vascular engineering is still available for future innovators that can take up the challenge to create a functional arterial substitute. [ABSTRACT FROM AUTHOR]

We proposed a method to determine the mechanical properties of electrospun nanofibers intended for use in vascular tissue engineering. Mechanical properties of poly(l-lactide) and poly(ε-caprolactone) copolymers and blends which are in fiber form were tested using the nanoindentation technique. Individual nanofibers were prone to give overweighed distributions in terms of E moduli in indentation testing. An increased compressive elastic modulus of 17 MPa was obtained in case of an increasing amount of poly(ε-caprolactone) in the fibers. It has also been found that the Hertzian model of compression is not adequate to model the elastic deformation of individual fibers. [ABSTRACT FROM AUTHOR]

Recently, nanomaterials have been widely utilized in tissue engineering applications due to their unique properties such as the high surface to volume ratio and diversity of morphology and structure. However, most methods used for the fabrication of nanomaterials are rather complicated and costly. Among different nanomaterials, anodic aluminum oxide (AAO) is a great example of nanoporous structures that can easily be engineered by changing the electrolyte type, anodizing potential, current density, temperature, acid concentration and anodizing time. Nanoporous anodic alumina has often been used for mammalian cell culture, biofunctionalization, drug delivery, and biosensing by coating its surface with biocompatible materials. Despite its wide application in tissue engineering, thorough in vivo and in vitro studies of AAO are still required to enhance its biocompatibility and thereby pave the way for its application in tissue replacements. Recognizing this gap, this review article aims to highlight the biomedical potentials of AAO for applications in tissue replacements along with the mechanism of porous structure formation and pore characteristics in terms of fabrication parameters. [ABSTRACT FROM AUTHOR]

Nanostructured biomaterials have great potential in the field of biomedical engineering. Efforts for treatment of cardiovascular diseases focused on introducing vascular substitutes that are nonthrombogenic and have long‐term patency, but still there is not any perfect replacement for clinical use. In this study, nanostructure tubes of a commonly known biocompatible polymer, polyethylene terephthalate (PET), were prepared via electrospinning process using small diameter mandrel as a collector with two different speeds. The nanofibers (NFs) morphologies' physical and mechanical properties were investigated according to scanning electron microscope (SEM), water contact angle (WCA), porosity measurement, differential scanning calorimetry (DSC), and tensile test. Finer NFs, more percentage of crystallinity, and superior mechanical properties were observed for samples prepared by higher speed mandrel. Since both samples stimulated platelet adhesion and activation, further surface modification with sodium nitrate as nitric oxide (NO) donor was done using two different approaches: dip‐coating and electrospraying. The modified NFs were evaluated via SEM, WCA, tensile test, platelets, and cell adhesion. The results showed more hydrophilicity, reduction in platelet adhesion, and improved blood compatibility for eNO‐HS (electrosprayed NO for higher collector speed) compared with other samples implying the promising potential of this fabrication and modification technique for improving PET‐based cardiovascular substitutes. [ABSTRACT FROM AUTHOR]

Morphology, hydrophilicity, degradation, mechanical properties, drug release, bacterial resistance, and cell viability are indispensable parameters for a bioactive wound dressing. In this work, the aforementioned terms between hybrid and blend nanofibrous samples based on poly (L-lactide-co-D, L-lactide) (PLDLLA) and poly (vinyl alcohol) (PVA) containing triclosan (Tri) as an antibacterial drug were investigated. The FE-SEM images showed that the presence of Tri in the hybrid and blend samples led to bimodal, and unimodal diameter size distributions. The FTIR spectra revealed that the addition of PVA caused to shift the carbonyl bond of PLDLLA in the blend sample, and DSC thermograms exhibited the immiscibility of PVA and PLDLLA polymers in the blend. Moreover, the hybrid sample showed higher hydrophilicity with water contact angle (WCA) of 53 ° than the blend ones with WCA of 73 ° which proved by water up-take test. In the following, the antibacterial evaluation showed better results for hybrid-Tri with the maximum growth inhibitory zones of 35 mm and 48 mm for E. coli and S. aureus, respectively. On the other hand, the hybrid nanofibrous sample showed remarkable mechanical properties (tensile stress ∼19 MPa, and Young's modulus ∼532 MPa). Finally, the SNL 76/7 fibroblast cell line culture confirmed that the hybrid-Tri nanofibrous sample had better proliferation performance than the blend-Tri sample because of the minimal cytotoxicity and maximal cell viability by MTT and acridine orange/ethidium bromide staining. [ABSTRACT FROM AUTHOR]

Developing a small‐diameter vascular graft with a satisfactory performance in terms of mechanical and biological properties remains a challenging issue because of comprehensive requirements from clinical applications. Polyvinyl alcohol (PVA)/polyacrylamide (PAAm) hydrogels exhibit many desirable characteristics for small‐diameter vascular grafts because of their tunable mechanical properties, especially high compliance. However, poor cells adhesion hinders their application for endothelialization in situ. Therefore, in the present work, polydopamine (PDA) and tetrapeptide Arg‐Glu‐Asp‐Val (REDV) were used to functionalize the hydrogels surface and improve cells adhesion. A series of characterizations were systematically conducted to examine the applicability of coated hydrogels to small‐diameter vascular grafts. Results showed that bare and coated hydrogels have appropriate structural stability, and no significant differences in tensile properties could be found after being coated with PDA or PDA‐REDV. The hydrophilicity of the hydrogels decreased with the coatings of PDA and especially PDA‐REDV to improve protein adsorption, porcine iliac artery endothelial cells (PIECs) adhesion, viability, proliferation, and spreading on the hydrogels. Lower hemolysis percentages and higher blood clotting index values were attained for the hydrogels, suggesting their satisfactory hemocompatibility. Overall, the present work provided insights into the development of a novel hydrogel‐based small‐diameter vascular graft. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:117–127, 2020. [ABSTRACT FROM AUTHOR]

The dissolution of collagen in ionic liquids (ILs) was highly dependent on the polarity of ILs, which was influenced by their sorts and concentrations. Herein, the solubility and dispersion degree of collagen in two sorts of ILs, namely 1-ethyl-methylimidazolium tetrafluoroborate ([EMIM][BF4]) with low polarity and 1-ethyl-3-methylimidazolium acetate ([EMIM][Ac]) with high polarity in a concentration range from 10% to 70% at 10 °C were investigated. When 150 mg of collagen was added to 30 mg of ILs, the minimum soluble collagen concentration was 0.02 mg/mL in 70% [EMIM][BF4] with lowest polarity and the maximum was 3.57 mg/mL in 70% [EMIM][Ac] with highest polarity, which indicates that soluble collagen and insoluble collagen fibers were both present. For insoluble collagens, differential scanning calorimetry showed that the thermal-stability was weakened when increasing the ILs concentration and polarity, and the fiber arrangement was looser with a more uniform lyophilized structure, observed by atomic force microscopy and scanning electron microscopy. For soluble collagens, electrophoresis patterns and Fourier transform infrared spectroscopy showed that no polypeptide chain degradation occurred during dissolution, but the thermal denaturation temperature decreased by 0.26 °C~ 7.63 °C with the increase of ILs concentrations, measured by ultra-sensitive differential scanning calorimetry. Moreover, the aggregation of collagen molecules was reduced when ILs polarity was increased as determined by fluorescence measurements and dynamic light scattering, which resulted in an increased loose fiber arrangement observed by atomic force microscopy. If the structural integrity of collagen needs to be retained, then the ILs sorts and concentrations should be considered. [ABSTRACT FROM AUTHOR]

Applications in additive manufacturing technologies for bone tissue engineering applications requires the development of new biomaterials formulations. Different three‐dimensional (3D) printing technologies can be used and polymers are commonly employed to fabricate 3D printed bone scaffolds. However, these materials used alone do not possess an effective osteopromotive potential for bone regeneration. A growing number of studies report the combination of polymers with minerals in order to improve their bioactivity. This review exposes the state‐of‐the‐art of existing 3D printed composite biomaterials combining polymers and minerals for bone tissue engineering. Characterization techniques to assess scaffold properties are also discussed. Several parameters must be considered to fabricate a 3D printed material for bone repair (3D printing method, type of polymer/mineral combination and ratio) because all of them affect final properties of the material. Each polymer and mineral has its own advantages and drawbacks and numerous composites are described in the literature. Each component of these composite materials brings specific properties and their combination can improve the biological integration of the 3D printed scaffold. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2579–2595, 2019. [ABSTRACT FROM AUTHOR]

This in vitro study aimed to evaluate the physicochemical and biological activity of the polycaprolactone/chitosan/collagen scaffolds incorporated with 0, 0.5, 3, and 6 wt% of graphene oxide (GO). Using standard tests and MG‐63 cells, the characteristics of scaffolds were evaluated, and the behavior of osteoblasts were simulated, respectively. A non‐significant decrease in nanofibers diameter was noted in scaffolds with a higher ratio of GO. The hydrophilicity and bioactivity of the scaffold surface, as well as cell attachment and proliferation, increased in correspondence to an increase in GO. The higher ratio of GO also improved the osteogenesis activity. GO increased the degradation rate, but it was negligible and seemed not enough to endanger stability. Modifying the scaffolds with GO did not make a significant change to the antibacterial effect. [ABSTRACT FROM AUTHOR]

Photoinduced network formation is an attractive strategy for designing water-insoluble gelatin fibres as medical device building blocks and for enabling late-stage property customisation. However, mechanically competent, long-lasting filaments are still hard to realise with current photoactive, e.g. methacrylated, gelatin systems due to inherent spinning instability and restricted coagulation capability. To explore this challenge, we present a multiscale approach combining the synthesis of 4-vinylbenzyl chloride (4VBC)-functionalised gelatin (Gel-4VBC) with a voltage-free spinning and UV-curing process so that biopolymer networks in the form of either individual fibres or nonwovens could be successfully manufactured. In comparison with state-of-the-art methacrylated gelatin, the mechanical properties of UV-cured Gel-4VBC fibres were readily modulated by adjustment of coagulation conditions, so that an ultimate tensile strength and strain at break of 25 ± 4–74 ± 3 MPa and 1.7 ± 0.3–8.6 ± 0.5% were measured, respectively. The sequential functionalisation/spinning route proved to be highly scalable, so that one-step spun-laid formation of fibroblast-friendly nonwoven fabrics was successfully demonstrated with wet-spun Gel-4VBC fibres. The presented approach could be exploited to generate a library of gelatin building blocks tuneable from the molecular to the macroscopic level to deliver computer-controlled extrusion of fibres and nonwovens according to defined clinical applications. [ABSTRACT FROM AUTHOR]