Poly(l‐Lactic Acid)/Gelatin Fibrous Scaffold Loaded with Simvastatin/Beta‐Cyclodextrin‐Modified Hydroxyapatite Inclusion Complex for Bone Tissue Regeneration

Recently, the application of nanostructured materials in the field of tissue engineering has garnered attention to mediate treatment and regeneration of bone defects. In this study, poly(l ‐lactic acid) (PLLA)/gelatin (PG) fibrous scaffolds are fabricated and β‐cyclodextrin (βCD) grafted nano‐hydroxyapatite (HAp) is coated onto the fibrous scaffold surface via an interaction between βCD and adamantane. Simvastatin (SIM), which is known to promote osteoblast viability and differentiation, is loaded into the remaining βCD. The specimen morphologies are characterized by scanning electron microscopy. The release profile of SIM from the drug loaded scaffold is also evaluated. In vitro proliferation and osteogenic differentiation of human adipose derived stem cells on SIM/HAp coated PG composite scaffolds is characterized by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and real time Polymerase chain reaction (PCR). The scaffolds are then implanted into rabbit calvarial defects and analyzed by microcomputed tomography for bone formation after four and eight weeks. These results demonstrate that SIM loaded PLLA/gelatin/HAp‐(βCD) scaffolds promote significantly higher ALP activity, mineralization, osteogenic gene expression, and bone regeneration than control scaffolds. This suggests the potential application of this material toward bone tissue engineering.

     

Preparation and characterization of nano‐platelet‐like hydroxyapatite/gelatin nanocomposites

Nature has succeeded in creating numerous bionanocomposites such as bones and teeth consisting of nano‐platelets and biopolymers. Understanding of the mechanisms of formation and of the relation between structure and properties is vital for development of new materials for biomedical and engineering applications. In this work, varying contents of nano‐platelet‐like hydroxyapatite (HAp) has been used to reinforce gelatin (Gel) to produce nanocomposites. The prepared HAp/Gel nanocomposites were characterized by X‐ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric (TG/DTG) analyses. XRD, TEM, and FTIR results confirm the synthesis of intercalated and exfoliated nanostructures depending on the amount of gelatin. TG results reveal that the intercalated HAp/gelatin nanocomposites show improved thermal properties as compared to pristine gelatin. The results reported here can be expanded to other HAp–polymer systems, thus paving a new way of designing and fabricating biomemitic nanocomposites for future engineering and particularly for biomedical applications. Copyright © 2010 John Wiley & Sons, Ltd.     

Biocompatible Crosslinked Nanofibers of Poly(Vinyl Alcohol)/Carboxymethyl‐Kappa‐Carrageenan Produced by a Green Process

This study presents a new type of biocompatible nanofiber based on poly(vinyl alcohol) (PVA) and carboxymethyl‐kappa‐carrageenan (CMKC) blends, produced with no generation of hazardous waste. The nanofibers are produced by electrospinning using PVA:CMKC blends with ratios of 1:0, 1:0.25, 1:0.4, 1:0.5, and 1:0.75 (w/w PVA:CMKC) in aqueous solution, followed by thermal crosslinking. The diameter of the fibers is in the nanometer scale and below 300 nm. Fourier transform infrared spectroscopy shows the presence of the carboxyl and sulfate groups in all the fibers with CMKC. The nanofibers from water‐soluble polymers are stabilized by thermal crosslinking. The incorporation of CMKC improves cytocompatibility, biodegradability, cell growth, and cell adhesion, compared to PVA nanofibers. Furthermore, the incorporation of CMKC modulates phenotype of human adipose‐derived stem cells (ADSCs). PVA/CMKC nanofibers enhance ADSC response to osteogenic differentiation signals and are therefore good candidates for application in tissue engineering to support stem cells.     

Hemocompatible and Bioactive Heparin‐Loaded PCL‐α‐TCP Fibrous Membranes for Bone Tissue Engineering

The combination of bioactive components such as calcium phosphates and fibrous structures are encouraging niche‐mimetic keys for restoring bone defects. However, the importance of hemocompatibility of the membranes is widely ignored. Heparin‐loaded nanocomposite poly(ε‐caprolactone) (PCL)‐α‐tricalcium phosphate (α‐TCP) fibrous membranes are developed to provide bioactive and hemocompatible constructs for bone tissue engineering. Nanocomposite membranes are optimized based on bioactivity, mechanical properties, and cell interaction. Consequently, various concentrations of heparin molecules are loaded within nanocomposite fibrous membranes. In vitro heparin release profiles reveal a sustained release of heparin over the period of 14 days without an initial burst. Moreover, heparin encapsulation enhances mesenchymal stem cell (MSC) attachment and proliferation, depending on the heparin content. It is concluded that the incorporation of heparin within TCP–PCL fibrous membranes provides the most effective cellular interactions through synergistic physical and chemical cues.     

Bioactive gelatin cryogels with BMP-2 biomimetic peptide and VEGF:A potential scaffold for synergistically induced osteogenesis

A poor biocompatibility and bioactivity of invasive materials remains major problems for biomaterialbased therapy. In this study, we introduced gelatin scaffolds carrying both bone morphogenetic protein-2(BMP-2) biomimetic peptide and vascular endothelial growth factor-165(VEGF) that achieved controlled release, cell attachment, proliferation and differentiation. To promote osteogenesis with VEGF, we designed the BMP-2 biomimetic peptide that comprised BMP-2 core sequence oligopeptide(SSVPT), ph...     

Improved efficacy of bio‐mineralization of human mesenchymal stem cells on modified PLLA nanofibers coated with bioactive materials via enhanced expression of integrin α2β1

Current therapeutic interventions in bone defects are mainly focused on finding the best bioactive materials for inducing bone regeneration via activating the related intracellular signaling pathways. Integrins are trans‐membrane receptors that facilitate cell‐extracellular matrix (ECM) interactions and activate signal transduction. To develop a suitable platform for supporting human bone marrow mesenchymal stem cells (hBM‐MSCs) differentiation into bone tissue, electrospun poly L‐lactide (PLLA) nanofiber scaffolds were coated with nano‐hydroxyapatite (PLLA/nHa group), gelatin nanoparticles (PLLA/Gel group), and nHa/Gel nanoparticles (PLLA/nHa/Gel group) and their impacts on cell proliferation, expression of osteoblastic biomarkers, and bone differentiation were examined and compared. MTT data showed that proliferation of hBM‐MSCs on PLLA/nHa/Gel scaffolds was significantly higher than other groups (P < .05). Alkaline phosphatase activity was also more increased in hBM‐MSCs cultured under osteogenic media on PLLA/nHa/Gel scaffolds compared to others. Gene expression evaluation confirmed up‐regulation of integrin α2β1 as well as the osteogenic genes BGLAP, COL1A1, and RUNX2. Following use of integrin α2β1 blocker antibody, the protein level of integrin α2β1 in cells seeded on PLLA/nHa/Gel scaffolds was decreased compared to control, which confirmed that most of the integrin receptors were bound to gelatin molecules on scaffolds and could activate the integrin α2β1/ERK axis. Collectively, PLLA/nHa/Gel scaffold is a suitable platform for hBM‐MSCs adhesion, proliferation, and osteogenic differentiation in less time via activating integrin α2β1/ERK axis, and thus it might be applicable in bone tissue engineering.     

Enzyme‐Catalyzed Crosslinking in a Partly Frozen State: A New Way to Produce Supermacroporous Protein Structures

In this study a new way to produce supermacroporous protein structures was investigated. Enzyme‐mediated crosslinking of gelatin or casein was performed in a partly frozen state, which yielded stable, protein‐based cryogels. The reaction kinetics for the formation of cryogels were found to be fairly slow, most likely due to the low temperature (?12 °C) used or due to an increased viscosity owing to the cryo‐concentration taking place. The produced cryogels were characterized with regards to their physical properties and in vitro degradation. Furthermore, cryogels produced from gelatin and casein were evaluated as potential scaffolds by fibroblast cultivation to confirm their in vitro biocompatibility. Gelatin‐ and casein‐based scaffolds both supported cell proliferation and migration through the scaffold.

     

Controlling the Poly(ε‐caprolactone) Degradation to Maintain the Stemness and Function of Adipose‐Derived Mesenchymal Stem Cells in Vascular Regeneration Application

Biodegradable poly(ε‐caprolactone) (PCL) scaffolds with adipose‐derived mesenchymal stem cells (ADSCs) have been used in vascular regeneration studies. An evaluation method of the effect of PCL degradation products (DP) on the viability, stemness, and differentiation capacities of ADSCs is established. ADSCs are cultured in medium containing different concentrations of PCL DP before evaluating the effect of PCL DP on the cell apoptosis and proliferation, cell surface antigens, adipogenic and osteogenic differentiation capacities, and capacities to differentiate into endothelial cells and smooth muscle cells. The results demonstrate that PCL DP exceed 0.05 mg mL^?1 may change the stemness and differentiation capacities of ADSCs. Therefore, to control the proper concentration of PCL DP is essential for ADSCs in vascular regeneration application.     

Covalent Incorporation of Heparin Improves Chondrogenesis in Photocurable Gelatin‐Methacryloyl Hydrogels

Multicomponent gelatin‐methacryloyl (GelMA) hydrogels are regularly adopted for cartilage tissue engineering (TE) applications, where optimizing chemical modifications for preserving biofunctionality is often overlooked. This study investigates the biological effect of two different modification methods, methacrylation and thiolation, to copolymerize GelMA and heparin. The native bioactivity of methacrylated heparin (HepMA) and thiolated heparin (HepSH) is evaluated via thromboplastin time and heparan sulfate‐deficient myeloid cell‐line proliferation assay, demonstrating that thiolation is superior for preserving anticoagulation and growth factor signaling capacity. Furthermore, incorporating either HepMA or HepSH in chondrocyte‐laden GelMA hydrogels, cultured for 5 weeks under chondrogenic conditions, promotes cell viability and chondrocyte phenotype. However, only GelMA‐HepSH hydrogels yield significantly greater differentiation and matrix deposition in vitro compared to GelMA. This study demonstrates that thiol‐ene chemistry offers a favorable strategy for incorporating bioactives into gelatin hydrogels as compared to methacrylation while furthermore highlighting GelMA‐HepSH hydrogels as candidates for cartilage TE applications.     

Super macroporous poly(N‐isopropyl acrylamide) cryogel for separation purpose

Polymers that can respond reversibly by changing their physical or chemical properties are recognized as stimuli‐responsive polymers. The renowned temperature‐sensitive polymer is poly(N‐isopropyl acrylamide) (p(NIPAM)), and here, homopolymeric supermacroporous p(NIPAM)) cryogel was synthesized via cryopolymerization technique at cryogenic condition (below melting point of solvent, −18°C). Then, the prepared p(NIPAM) cryogel was characterized via scanning electron microscopy, Fourier transform infrared radiation spectrometer, and thermogravimetric analyzer. The lower critical solution temperature (LCST) value of the prepared p(NIPAM) cryogel was determined from % swelling equilibrium swellings at various temperatures, 20, 25, 30, 35, 40, 45, and 50°C, respectively. Furthermore, the pore volume and porosity of p(NIPAM) cryogels were compared below and above the LCST values. Finally, the separation capability of p(NIPAM) cryogels for some molecules such as tannic acid, gallic acid, nicotine (N), and caffeine (C) was investigated at the below and above the LCST values.     

Preparation and characterization of polyoxymethylene‐copolymer/hydroxyapatite nanocomposites for long‐term bone implants

In this work, new polyoxymethylene (POM)/hydroxyapatite (HAp) nanocomposites for long‐term bone implants have been obtained via extrusion and injection molding processes and characterized by differential scanning calorimetry (DSC), temperature‐modulated DSC (TMDSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), wide‐angle X‐ray diffraction (WAXD), Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG), and tensile mechanical and in vitro stability tests. Based on the DSC results, it was found that the degree of crystallinity increases for POM/0.5% HAp sample and decreases for POM/1.0% HAp and POM/2.5% HAp. SEM and TEM observations for POM/HAp nanocomposites indicated that the dispersion of HAp in the polymer matrix was uniform and the diameter of the HAp particles was less than 100 nm for most of them. Young's modulus increases with increasing HAp concentration, whereby elongation at break decreases. On the contrary, HAp concentration does not have a significant influence on the tensile strength. TG results show that for POM/0.5% HAp, POM/1.0% HAp, and POM/2.5% HAp, thermal stability slightly increases in comparison to pure POM, whereas for POM/5.0 HAp and POM/10.0% HAp, lower thermal stability was observed. In vitro data reveal that with an increase of HAp content, bioactivity of nanocomposites increases; a good in vitro chemical stability of POM and POM nanocomposites was confirmed. Copyright © 2011 John Wiley & Sons, Ltd.     

Fabrication and properties of mineralized collagen‐chitosan/hydroxyapatite scaffolds

A hydroxyapatite (HAp)/biopolymer composite scaffold was fabricated by mineralizing a crosslinked collagen/chitosan, which was pre‐mineralized with Ca²⁺ and phosphate salts, in simulated body fluid (SBF) for only 24 hr. A self‐organized structure similar to bone is expected. Microstructures of the crosslinked collagen/chitosan scaffold, the pre‐mineralized collagen–chitosan scaffold (CCS), and the mineralized collagen‐chitosan/HAp scaffolds (MCCHS) were characterized by scanning electron microscopy (SEM), revealing non‐alteration of the porous structure and formation of the HAp particles. X‐ray diffractometer (XRD) confirmed the crystalline structure of the HAp. Thermal gravimetric analysis found that more HAp particles were formed when the CCSs were pre‐mineralized in a higher concentration of Ca²⁺. Water‐uptake ratio of the crosslinked CCS was ～160, decreased to ～120 after incubating in Ca²⁺ solution, and further decreased to ～20 after mineralization. Mechanical strength of the CCS was improved significantly after the in situ mineralization too. The method introduced here may be potentially applied to obtain other biopolymer/HAp composite in a short period. Copyright © 2008 John Wiley & Sons, Ltd.     

Electrospun Heparin‐Loaded Core–Shell Nanofiber Sutures for Achilles Tendon Regeneration In Vivo

Achilles tendon reconstruction surgery is the primary clinical method for repairing acute Achilles tendon ruptures. However, the efficacy of the postoperative healing process and the recovery of physiological function are inadequate. This study examines the healing mechanism of ruptured rat Achilles tendons seamed with heparin‐loaded core–shell fiber sutures fabricated via near‐field electrospinning. High‐heparin‐concentration sutures (PPH3.0) perform better than the low‐heparin‐concentration sutures and commercial sutures (CSs). The PPH3.0 suture recruits fewer inflammatory cells and shows good histocompatibility in peritoneal implantation experiments. Staining of the Achilles tendon rupture repair zone demonstrates that a high heparin concentration in sutures reduces immune‐inflammatory responses. Immunohistochemical analysis reveals that the transforming growth factor‐β staining scores of the PPH3.0 sutures are not significantly different from those of the corresponding control group but are significantly different from those of the CSs and non‐heparin‐loaded‐suture groups. According to vascular endothelial growth factor (VEGF) analysis, the concentration of VEGF in the group treated with the PPH3.0 suture increases by 37.5% compared with that in its control group. No significant difference in tension strength is observed between the PPH3.0 group and healthy Achilles tendons. These findings illustrate that this novel method effectively treats Achilles tendon rupture and promotes healing and regeneration.     

Genipin‐crosslinked gelatin hydrogel incorporated with PLLA‐nanocylinders as a bone scaffold: Synthesis,characterization, and mechanical properties evaluation

Nowadays, despite remarkable progress in developing bone tissue engineering products, the fabrication of an ideal scaffold that could meet the main criteria, such as providing mechanical properties and suitable biostability as well as mimicking the bone extracellular matrix, still seems challenging. In this regard, utilizing combinatorial approaches seems more beneficial. Here, we aim to reinforce the mechanical characteristics of gelatin hydrogel via a combination of Genipin‐based chemical cross‐linking and incorporation of the poly l ‐lactic acid (PLLA) nanocylinders for application as bone scaffolds. Amine‐functionalized nanocylinders are prepared via the aminolysis procedure and incorporated in gelatin hydrogel. The nanocylinder content (0, 1, 2, 3, and 4 wt%) and cross‐linking density (0.1, 0.5, and 1 wt/vol%) are optimized to achieve suitable morphology, swelling ratio, degradation rate, and mechanical behaviors. The results indicate that hydrogel scaffold cross‐linking by 0.5 wt% of Genipin shows optimized morphological feathers with a pore size of around 300 to 500 μm as well as an average degradation rate (40.09% ± 3.08%) during 32 days. Besides, the incorporation of 3 wt% PLLA nanocylinders into the cross‐linked gelatin scaffold provides an optimized mechanical reinforcement as compressive modulus, and compressive strength show a 4‐ and 2.6‐fold increase, respectively. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay indicates that the scaffold does not have any cytotoxicity effect. In conclusion, gelatin composite reinforced with 3 wt% PLLA nanocylinders cross‐linked via 0.5 wt/vol% Genipin is suggested as a potential scaffold for bone tissue engineering applications.     

Exploring peptide‐functionalized alginate scaffolds for engineering cardiac tissue from human embryonic stem cell‐derived cardiomyocytes in serum‐free medium

Engineering human cardiac tissue is a promising solution for myocardial repair of injured hearts and for drug screening. Herein, we examined the capability of chemically defined alginate scaffolds to promote cardiac tissue regeneration from human embryonic stem cell‐derived cardiomyocytes (hESC‐CMs) in serum‐free, chemically defined medium. The cells were single seeded or coseeded with human dermal fibroblasts (HFs) in macroporous scaffolds made from pristine alginate or alginate modified with arginine‐glycine‐aspartate (RGD) peptide and heparin‐binding peptide (HBP). Our results show that the addition of fibroblasts to the 3‐D culture is indispensable for the formation of functional cardiac tissues and that the presence of RGD/HBP attached to the alginate matrix further improves its functionality. The engineered tissue displayed the typical fiber morphology with massive striation. An increase in contraction amplitude and calcium transients with time, together with a decrease in excitation threshold, indicated advancement toward tissue maturation. Our results thus point to the importance of co‐cultivating fibroblasts with hESCs‐CMs in chemically defined peptide‐functionalized alginate scaffolds and culture medium for regenerating functional cardiac tissue in vitro.     

One‐step Preparation of Carbon‐based Solid Acid Catalyst from Water Hyacinth Leaves for Esterification of Oleic Acid and Dehydration of Xylose

Carbon‐based solid acid catalysts were successfully obtained via one‐step hydrothermal carbonization (HTC) of water hyacinth (WH) in the presence of p ‐toluenesulfonic acid (PTSA). Increasing the HTC temperature from 180 to 240 °C resulted in carbonaceous materials with increased sulfur content and less adsorbed water. The material obtained at 220 °C (WH‐PTSA‐220) contains the highest amount of acid sites and promotes the highest initial rate of two transformations, that is, methanolysis of oleic acid and dehydration of xylose to furfural. While all PSTA‐treated WH catalysts gave comparable fatty acid conversions (≈97 %) and furfural yields (≈60 %) after prolonged reaction times, the WH‐PTSA‐240 system bearing a relatively low acid density maintains the most favorable reusability profile. Higher HTC temperatures (220–240 °C) improved the catalyst reusability profiles due to graphitization and hydrophobicity of the carbon surface. The catalyst systems derived herein from biomass may have potential applications in biorefining platforms, utilizing the conversion of waste biomass to chemicals.     

Drug‐Loaded Elastin‐Like Polypeptide–Collagen Hydrogels with High Modulus for Bone Tissue Engineering

Emphasizing the role of hydrogel stiffness and cellular differentiation, this study develops collagen and elastin‐like polypeptide (ELP)–based bone regenerative hydrogels loaded with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and doxycycline with mechanical properties suitable for osteogenesis. The drug‐incorporated collagen–ELP hydrogels has significantly higher modulus of 35 ± 5 kPa compared to collagen‐only hydrogels. Doxycycline shows a bi‐phasic release with an initial burst release followed by a gradual release, while rhBMP‐2 exhibits a nearly linear release profile for all hydrogels. The released doxycycline shows anti‐microbial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, and Escherichia coli. Microscopic observation of the hydrogels reveals their interconnected, macroporous, 3D open architecture with pore diameters between 160 and 400 µm. This architecture supports human adipose–derived stem cell attachment and proliferation from initial days of cell seeding, forming a thick cellular sheath by day 21. Interestingly, in collagen and collagen–ELP hydrogels, cell morphology is elongated with stretched slender lamellipodial formation, while cells assemble as spheroidal aggregates in crosslinked as well as drug‐loaded hydrogels. Osteogenic markers, alkaline phosphatase and osteocalcin, are expressed maximally for drug‐loaded hydrogels compared to those without drugs. The drug‐loaded collagen–ELP hydrogels are thus promising for combating bacterial infection and promoting guided bone regeneration.     

Film‐formation property of vinylidene chloride‐methyl methacrylate copolymer latex. I. Effect of emulsion‐polymerization process

Changes in minimum film‐formation temperature (MFFT) during storage of latexes prepared from 91:9 wt % vinylidene chloride (VDC)‐methyl methacrylate (MMA) monomer mixture by seeded batch and seeded semicontinuous emulsion polymerization were investigated, with attention centered on polymer‐crystallization behavior during storage in the dispersed state. MFFT of latex prepared by the seeded batch process rose to 47 °C, whereas that of latex prepared by seeded semicontinuous process remained below 14 °C with storage at 20 °C for 12 weeks. Infrared absorption of latexes in the dispersed state and wide‐angle X‐ray diffraction of powder polymers obtained by lyophilization of fresh and stored latexes both indicated a much greater increase in polymer crystallinity during storage with latex prepared by the seeded batch process than with that prepared by the seeded semicontinuous process. Analysis of the copolymer composition drift calculated from reactivity ratios and ¹H NMR analysis indicated a wider sequence distribution and longer VDC sequences in polymer prepared by the seeded batch process than in polymer prepared by the seeded semicontinuous process. This explained the higher rate of crystallization during storage with latex prepared by the seeded batch process than with that prepared by the seeded semicontinuous process. Rising crystallinity during storage in the dispersed state is believed to have caused the MFFT rise. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 939–947, 2002     

Strontium‐Substituted Hydroxyapatite‐Gelatin Biomimetic Scaffolds Modulate Bone Cell Response

Strontium has a beneficial role on bone remodeling and is proposed for the treatment of pathologies associated to excessive bone resorption, such as osteoporosis. Herein, the possibility to utilize a biomimetic scaffold as strontium delivery system is explored. Porous 3D gelatin scaffolds containing about 30% of strontium substituted hydroxyapatite (SrHA) or pure hydroxyapatite (HA) are prepared by freeze‐drying. The scaffolds display a very high open porosity, with an interconnectivity of 100%. Reinforcement with further amount of gelatin provokes a modest decrease of the average pore size, without reducing interconnectivity. Moreover, reinforced scaffolds display reduced water uptake ability and increased values of mechanical parameters when compared to as‐prepared scaffolds. Strontium displays a sustained release in phosphate buffered saline: the quantities released after 14 d from as‐prepared and reinforced scaffolds are just 14 and 18% of the initial content, respectively. Coculture of osteoblasts and osteoclasts shows that SrHA‐containing scaffolds promote osteoblast viability and activity when compared to HA‐containing scaffolds. On the other hand, osteoclastogenesis and osteoclast differentiation are significantly inhibited on SrHA‐containing scaffolds, suggesting that these systems could be usefully applied for local delivery of strontium in loci characterized by excessive bone resorption.     

Design,Preparation, and Performance of a Novel Bilayer Tissue‐Engineered Small‐Diameter Vascular Graft

In clinical practice, the need for small‐diameter vascular grafts continues to increase. Decellularized xenografts are commonly used for vascular reconstructive procedures. Here, porcine coronary arteries are decellularized, which destroys the extracellular matrix structure, leading to the decrease of vascular strength and the increase of vascular permeability. A bilayer tissue‐engineered vascular graft (BTEV) is fabricated by electrospinning poly(l ‐lactide‐co‐carprolactone)/gelatin outside of the decellularized vessels and functionalized by immobilizing heparin, which increases the biomechanical strength and anticoagulant activity of decellularized vessels. The biosafety and efficacy of the heparin‐modified BTEVs (HBTEVs) are verified by implanting in rat models. HBTEVs remain patent and display no expansion or aneurism. After 4 weeks of implantation, a cell monolayer in the internal surface and a dense middle layer have formed, and the mechanical properties of regenerated vessels are similar to those of rat abdominal aorta. Therefore, HBTEVs can be used for rapid remodeling of small‐diameter blood vessels.