BACKGROUND:With the increasing aging of population, the incidence rate of diseases such as fracture and osteoporosis has been increasing. The demand for implant in Department of orthopedics has increased. The elastic modulus of the existing solid metal implant is much higher than that of human bonetissue, and it is easy to produce stress shielding effect after operation, which causes complications such as loosening of prosthesis and low fusion efficiency. OBJECTIVE:In order to solve the mismatch of elastic modulus between solid metal orthopedic implants and human bone tissue, metal structures with excellent mechanical properties were prepared. METHODS:The porous structure was designed by spatial dot matrix method, and the metal porous structure was prepared based on selective laser melting 3D printing technology. The residual stress in the preparation process was eliminated by vacuum annealing heat treatment, and the static compression experiment was carried out to study the effects of different pore shape and porosity parameters on the compressive yield strength and elastic modulus of porous structure. The performance changes of porous structure before and after heat treatment were compared, and the porous structure meeting the performance requirements of human bone tissue was selected. RESULTS:The porous structure prepared by selective laser melting technology met the requirements of human bone tissue. The elastic modulus was as low as 0.74 GPa and the compressive yield strength is 201.91 MPa; After annealing heat treatment, the compressive yield strength of porous structure decreased, the maximum change was 3.69%, the elastic modulus increased, and the maximum change was 8.69%. CONCLUSIONS:For the porous structure with the same pore shape, the lower the porosity, the better the mechanical properties of the porous structure. For the same porosity, the comprehensive mechanical properties of dodecahedral porous structure were the best and octahedral porous structure was the worst; The porous structure after annealing heat treatment was more conducive to meet the performance requirements of human bone tissue.

BACKGROUND:Elastin is a fibrous protein key to the structure and support of skin as well as other organ tissues. Elastic fibers are located in the skin’s dermal layer and make up approximately 2%–4% of the fat-free dry weight of the dermis in the skin of adults. Aging causes the progressive degradation of elastin fibers. Loss of these fibers can cause skin sagging and wrinkling, loss of healthy blood vessels and lung capacity, aneurysms, and Chronic Obstructive Pulmonary Disease (COPD). OBJECTIVE:We hypothesized that ellagic acid, a polyphenol, will increase elastin in human dermal fibroblasts (HDF) due to polyphenols’ elastin binding properties. METHOD:We treated HDF’s with 2 μg/ml ellagic acid for 28 days to see the elastin deposition in HDF cell cultures. To test this, we treated HDFs with polyphenols ellagic acid for 3, 7, 14 and 21 days. For comparison purposes, we included a group of ellagic acid and retinoic acid since retinoic acid is already in the market for elastin regeneration purposes. RESULTS:When ellagic acid and retinoic acid were introduced together, insoluble elastin and collagen deposition were significantly higher in HDFs compared to other groups. CONCLUSION:Polyphenols and retinoic acid can improve skin extracellular matrix production of elastin and collagen and may improve skin fine wrinkles.

BACKGROUND:Calcium phosphates including β-tricalcium phosphate (β-TCP) and hydroxyapatite (HAp) have been widely used for bone regeneration application because of their high osteoconductive activities. In addition, various kinds of inorganic ions enhance differentiation, proliferation, and mineralization of osteoblasts. However, information about the effects of silver-doped β-TCP [β-TCP (Ag)] and HAp [HAp (Ag)] particles on osteogenic differentiation is not available yet. OBJECTIVE:We focused on the impact of β-TCP (Ag) and HAp (Ag) particles on the osteogenic differentiation of MC3T3-E1 osteoblast precursor cells. METHODS:MC3T3-E1 osteoblast precursor cells were pre-treated by β-TCP (Ag) or HAp (Ag). And then the medium was changed to differentiation medium. Subsequently, osteoblast differentiation-related markers were determined. RESULTS:We found that treatment with β-TCP (Ag) or HAp (Ag) particles increased alkaline phosphatase activity in MC3T3-E1 cells. Expression of osteoblast differentiation-related genes also increased after treatment with β-TCP (Ag) or HAp (Ag) particles, a response thought to be regulated by zinc finger-containing transcription factor osterix. The ratio of the receptor activator of nuclear factor kappa-B ligand (RANKL) to osteoprotegerin (OPG) was decreased by β-TCP (Ag) and HAp (Ag) particles. CONCLUSION:Silver doping of β-TCP and HAp particles is effective for bone regeneration.

BACKGROUND:Microcirculation plays a key role in regulating blood flow but is not considered in previous research of hemodynamics. OBJECTIVE: A curved artery model is established to study its hemodynamic characteristics based on microcirculation boundary. METHODS:The hemodynamic model of a curved artery is constructed and simulated by computational fluid dynamics. The curved artery model is simulated by fluid-structure interaction. At the same time, a porous medium is used to simulate microcirculation as the outlet boundary. RESULTS:The distribution characteristics of the blood flow velocity, the pressure and the wall shear stress in different sections at different time of the cardiac cycle are obtained. The results show that the velocities in curved arteries decrease and the pressures gradually increase. The blood flow velocity waveform and value are affected and they are sensitive to the microcirculation boundary. However, the pressure value is only affected by the microcirculation function. CONCLUSIONS: This work is useful for researchers to deeply understand the hemodynamic characteristics of curved arteries. There is important clinical significance to analyze the pathogenesis of cardiovascular disease considering microcirculation function and its coupling effect.

BACKGROUND:Arteriovenous fistula (AVF) is the preferred route of vascular access in hemodialysis. The primary reason of fistula failure is Intimal hyperplasia (IH), which leads to stenosis. Wall shear stress (WSS) and disturbed flow are the critical parameters in the formation of IH. OBJECTIVE:Theprimary goal of this study is to explore the influence of anastomosis angle on WSS and venous outflow rate, as well as to find the ideal angle of anastomosis for AVF to standardize surgical technique. METHODS:Three-dimensional idealized geometries of end-to-side type AVF for the five various angles of anastomosis are considered in this study. The WSS, blood flow rate at the venous outlet for non-Newtonian, pulsatile blood flow are calculated using a numerical simulation technique. RESULTS:The WSS is higher at 75° compared to other angles and least at 45° for pulsating arterial inflows. The WSS is moderate at 30°, 60° and 90°. On the arterial bed and outer wall of the vein, immediately after the anastomosis, the recirculation zone is observed. At an angle of 45° and 90° anastomosis, the outflow rate is greater at distal venous end. CONCLUSIONS:If one believes that high wall shear stress causes IH within the AVF, the results suggest that the AVF should be formed at a 45° angle to avoid IH. However, if one believes that low wall shear stress causes IH within the AVF, the results suggest that AVF should be formed at either 30° or 75° to avoid IH. The findings spotlight the importance of anastomosis angle in determining AVF hemodynamics.

BACKGROUND:At present, surgical resection and chemotherapy are still the main treatments for hepatocellular carcinoma and other cancers, but the curative effect and survival rate are not ideal. OBJECTIVE:In this study, we aim to prepare a carrier with low toxicity, high biocompatibility and targeted transport for the treatment of hepatocellular carcinoma. METHODS:CdSe quantum dots (QDs) modified with oleic acid were synthesized. Then hydrophobic CdSe QDs and hydrophilic super-paramagnetic Fe3O4 particles were encapsulated into different layers of liposomes to form magnetic fluorescent liposomes (MFLs). MFLs in the aqueous would quickly drift towards the external magnet and the entire process was clearly observed with fluorescence microscope. The fluorescence spectra revealed that the fluorescence properties of MFLs were similar to that of CdSe QDs. RESULTS:QDs had an average size of 3.32 nm with good fluorescence properties. The size of MFLs was about 100 nm (transmission electron microscopy (TEM) analysis showed the average size of MFLs was about 82.8 nm and dynamic light scattering (DLS) detection showed 111.9 nm). After being cultured with MFLs for 8 h, HepG2 cells were labeled by MFLs and good fluorescence images were obtained. MTT analysis also expressed their good biocompatibility. CONCLUSION:The prepared MFLs had multi-function and could be used as ideal drug carriers.

BACKGROUND:The necessity to manufacture scaffolds with superior capabilities of biocompatibility and biodegradability has led to the production of extracellular matrix (ECM) scaffolds. Among their advantages, they allow better cell colonization, which enables its successful integration into the hosted tissue, surrounding the area to be repaired and their formulations facilitate placing it into irregular shapes. The ECM from porcine urinary bladder (pUBM) comprises proteins, proteoglycans and glycosaminoglycans which provide support and enable signals to the cells. These properties make it an excellent option to produce hydrogels that can be used in regenerative medicine. OBJECTIVE:The goal of this study was to assess the biocompatibility of an ECM hydrogel derived from the porcine urinary bladder (pUBMh) in vitro using fibroblasts, macrophages, and adipose-derived mesenchymal stem cells (AD-MCSs), as well as biocompatibility in vivo using Wistar rats. METHODS:Effects upon cells proliferation/viability was measured using MTT assay, cytotoxic effects were analyzed by quantifying lactate dehydrogenase release and the Live/Dead Cell Imaging assay. Macrophage activation was assessed by quantification of IL-6, IL-10, IL-12p70, MCP-1, and TNF-α using a microsphere-based cytometric bead array. For in vivo analysis, Wistar rats were inoculated into the dorsal sub-dermis with pUBMh. The specimens were sacrificed at 24 h after inoculation for histological study. RESULTS:The pUBMh obtained showed good consistency and absence of cell debris. The biocompatibility tests in vitro revealed that the pUBMh promoted cell proliferation and it is not cytotoxic on the three tested cell lines and induces the production of pro-inflammatory cytokines on macrophages, mainly TNF-α and MCP-1. In vivo, pUBMh exhibited fibroblast-like cell recruitment, without tissue damage or inflammation. CONCLUSION:The results show that pUBMh allows cell proliferation without cytotoxic effects and can be considered an excellent biomaterial for tissue engineering.

BACKGROUND:Collagen production in fibroblasts is important for skin tissue repair. Cell-adhesive Arg-Gly-Asp (RGD) peptides immobilized on scaffolds stimulate fibroblast collagen production, but RGD peptides in solution exhibit opposite effects. Transgenic silkworm technology enables the design offusion positions for RGD peptides in silk fibroin molecules. The effect of RGD-fused silk fibroin in solution on fibroblast cell activity remains unclear. OBJECTIVE:To clarify the effects of RGD peptides fused to silk fibroin heavy (H)-chain or light (L)-chain on fibroblast proliferation and collagen production when RGD-fused silk fibroin proteins were added to the culture medium. METHODS:Silk fibers with RGD-fused H-chains (H-RGD) or L-chains (L-RGD) were degummed, dissolved, and dialyzed to prepare H-RGD or L-RGD aqueous solutions, respectively. These solutions were added to the fibroblast medium, and their proliferation and collagen production were quantified. RESULTS:Both L- and H-RGD stimulated fibroblast proliferation at a similar level, even in a solution format, but L-RGD promoted fibroblast collagen production significantly, indicating the synergistic effect of the native H-chain and RGD-fused L-chain. CONCLUSION:RGD-fused silk fibroin in solution stimulated fibroblast proliferation and collagen production, depending on the fusion position of the peptides.

BACKGROUND:The COVID-19 pandemic has resulted in increased psychological pressure on mental health since 2019. The resulting anxiety and stress have permeated every aspect of life during confinement. OBJECTIVE:To provide psychologists with an unbiased measure that can aid in the preliminary diagnosis of anxiety disorders and be used as an initial treatment in cognitive-behavioral therapy, this article introduces automated recognition of three levels of anxiety. METHODS:Anxiety was elicited by exposing participants to virtual environments inspired by social situations in reference to the Liebowitz social anxiety scale. Relevant parameters, such as heart rate variability and vasoconstriction were derived from the measurement of the blood volume pulse (BVP) signal. RESULTS:A long short-term memory architecture achieved an accuracy of approximately 98% on the training and test set. CONCLUSION:The generated model allowed for careful study of the state of seven phobic participants during virtual reality exposure (VRE).

BACKGROUND:There is currently no methodology for evaluating the accuracy of ablation in ablation therapy, and thus normal cells in the surrounding area can be damaged, possibly leading to complications. OBJECTIVE:The aim of this study was to distinguish heat-treated dead cells from viable cells using the electrical impedance-to-frequency ratio as an evaluation index. METHODS:Rat heart striated myocytes were cultured in a monolayer on collagen-coated microelectrodes placed in the center of an electrode-loaded chamber. The cells in the chamber were killed by heat treatment for 5 minutes at 50 °C, and the frequency response of the cell impedance was measured before and after heat treatment. The frequency of the input current was varied from 10 to 100 kHz. The measured electrical impedance at each frequency was divided by the value at 100 kHz, and we refer to the resulting values as the impedance ratio. RESULTS:The impedance ratio was high at low frequencies and low at high frequencies. Furthermore, the impedance ratio was lower at lower frequencies after heat treatment than before heat treatment. CONCLUSIONS:The electrical impedance ratio can be used to distinguish viable and dead cells after heat treatment.

BACKGROUND:Closed-wedge high tibial osteotomy (CWHTO) with a fibular osteotomy (FO) causes medial joint space widening in the knee. However, the effect of FO on the joint space width remains unclear. OBJECTIVE:This study aimed to examine the effect of FO on the knee in HTO. METHODS:A compression load test was performed on two amputated human limbs under four conditions: (1) normal (without any osteotomy), (2) open-wedge HTO (OWHTO), (3) OWHTO with FO, and (4) CWHTO. The contact area of the femoral and tibial cartilages and the medial and lateral joint space widths in each condition were evaluated using a motion capture system with computed tomography (CT) and magnetic resonance imaging (MRI) data. RESULTS:The contact area increased on the lateral side after OWHTO, which increased more on the lateral side with a concomitant decrease on the medial side in both subjects when FO was added to OWHTO. An increase in the medial joint space width and a decrease on the lateral side were seen in both OWHTO with FO and CWHTO. CONCLUSIONS:The contact area and joint space widths are affected by the FO, and the effect is more pronounced than the way of HTO (OWHTO or CWHTO).

BACKGROUND:Calcium phosphate cements (CPCs) are biocompatible materials that have been evaluated as scaffolds in bone tissue engineering. At present, the stem cell density of inoculation on CPC scaffold varies. OBJECTIVE:The aim of this study is to analyze the effect of seeding densities on cell growth and osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) on a calcium phosphate cements (CPCs) scaffold. METHODS:BMMSCs derived from minipigs were seeded onto a CPC scaffold at three densities [1 million/mL (1M), 5 million/mL (5M) and 25 million/mL 25M)], and cultured for osteogenic induction for 1, 4 and 8 days. RESULTS:Well adhered and extended BMMSCs on the CPC scaffold showed significantly different proliferation rates within each seeding density group at different time points (P < 0.05). The number of live cells per unit area in 1M, 5M and 25M increased by 3.5, 3.9 and 2.5 folds respectively. The expression of ALP peaked at 4 days post inoculation with the fold-change being 2.6 and 2.8 times higher in 5M and 25M respectively as compared to 1M. The expression levels of OC, Coll-1 and Runx-2 peaked at 8 days post inoculation. CONCLUSIONS:An optimal seeding density may be more conducive for cell proliferation, differentiation, and extracellular matrix synthesis on scaffolds. We suggest the optimal seeding density should be 5 million/mL.

BACKGROUND:Biological hydroxyapatite (BHA)-based bone grafting materials have been widely used for bone regeneration in implant surgery. Much effort has been made in the improvement of their osteogenic property as it remains unsatisfactory for clinical use. Osteoimmunomodulation plays a significantrole in bone regeneration, which is highly related to active inorganic ions. Therefore, attempts have been made to obtain osteoimmunomodulatory BHA-based bone grafting materials with optimized osteogenic property by ion doping. OBJECTIVE:To summarize and discuss the active inorganic ions doped into BHA and their effects on BHA-based bone grafting materials. METHOD:A literature search was performed in databases including Google Scholar, Web of Science and PubMed, with the elementary keywords of “ion doped” and “biological hydroxyapatite”, as well as several supplementary keywords. All document types were included in this search. The searching period and language were not limited and kept updated to 2022. RESULTS:A total of 32 articles were finally included, of which 32 discussed the physiochemical properties of BHA-based biomaterials, while 12 investigated their biological features in vitro, and only three examined their biological performance in vivo. Various ions were doped into BHA, including fluoride, zinc, magnesium and lithium. Such ions improved the biological performance of BHA-based biomaterials, which was attributed to their osteoimmunomodulatory effect. CONCLUSION:The doping of active inorganic ions is a reliable strategy to endow BHA-based biomaterials with osteoimmunomodulatory property and promote bone regeneration. Further studies are still in need to explore more ions and their effects in the crosstalk between the skeletal and immune systems.

BACKGROUND:Acute liver failure is one of the most intractable clinical problems. The use of bioartificial livers may solve donor shortage problems. Human umbilical cord mesenchymal stem cells (hUCMSCs) are an excellent seed cell choice for artificial livers because they change their characteristicsto resemble hepatocyte-like cells (HLCs) following artificial liver transplantation. OBJECTIVE:This study aimed to determine whether the immunological characteristics of hUCMSCs are changed after being transformed into hepatocyte-like cells. METHODS:HUCMSCs were isolated by the adherent method. The following hUCMSC surface markers were detected using flow cytometry: CD45, CD90, CD105, CD34, and octamer-binding transcription factor 4 (OCT-4). Functional detection of adipogenic differentiation was performed. The hUCMSCs were cultured in complete medium (control group) or induction medium (induction group), and flow cytometry was used to detect cell surface markers. Peritoneal lavage fluid was collected after intraperitoneal injection of 1 × 106 cells/mouse over 40 minutes. The leukocyte count, labeled CD45, CD3, CD4 and CD8 antibodies, and flow detection of T lymphocyte subsets were determined using the peritoneal lavage fluid. RESULTS:Using phenotypic and functional identification, hUCMSCs were successfully isolated using a two-step induction method. The surface markers of the hUCMSCs cells changed after HLC induction. In vivo immune results showed that hUCMSCs and HLsC induced leukocyte production. CONCLUSION:Hepatic induction of hUCMSCs changes their cell surface markers. Both HLCs and hUCMSCs cause leukocytosis in vivo, but the immune response induced by HLCs is slightly stronger.

BACKGROUND:Human adipose-derived stem cells have been identified as a promising candidate for cell-assisted therapy to improve graft survival. OBJECTIVE:To objective of the study was to add human adipose-derived stem cells into filling materials. METHODS:The filling materials were prepared and divided into 6 groups: fat particles with phosphate buffer saline or human adipose-derived stem cells; acellular dermal matrix particles with phosphate buffer saline or human adipose-derived stem cells; mixture of fat particles and acellular dermal matrix particles with phosphate buffer saline or human adipose-derived stem cells. The survival rate, vascular density and histological at 2, 6 and 12 weeks were investigated. RESULTS:Human adipose-derived stem cells significantly improved survival rate in each group at 6 and 12 weeks, and it significantly increased the vascular density in the fat particles and porcine acellular dermal matrix combined group and porcine acellular dermal matrix group at three time points, but human adipose-derived stem cells did not have a significant effect in the fat particles group. CONCLUSION:Human adipose-derived stem cells as assisted cells added into filling material can improve survival rate and vascular density in rats.

BACKGROUND:Polymerization conditions affect the physical-mechanical properties of acrylic resins used for craniofacial prostheses. OBJECTIVE:The aim of this study was to evaluate the effect of microwave polymerization on the thermomechanical properties and surface morphology of ocular prostheses fabricated with polymethyl methacrylate (PMMA). METHODS:PMMA discs were polymerized with microwave energy and with conventional heat polymerization (CHP) method. Ocular prostheses were fabricated to determine whether there were changes according to the polymerization method. The surface morphology and roughness were observed under SEM and AFM. The Vickers Hardness number (VHN) and flexural strength were measured. Thermal properties were evaluated with TGA/DSC, and chemical composition with FTIR. RESULTS:The PMMA acrylic resin polymerized with microwave energy showed a smooth surface with some relief areas. In the internal surface of the ocular prosthesis with microwave energy the PMMA is more compact. The mean roughness values were higher and statistically significant with CHP (P < 0.05), while the surface hardness and flexural strength were higher with microwave energy (P < 0.05). CONCLUSION:There were no changes in the calorimetry with either method, TGA showed an exothermic peak around 120 °C with CHP method. PMMA polymerized with microwave energy improved the mechanical and surface properties of the ocular prostheses.

BACKGROUND:Percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP) are commonly employed for Kummell’s disease in stages II–III; however, these techniques produce some complications. OBJECTIVE:To compare the clinical efficacy and imaging results of percutaneous vertebroplasty + bone cement-augmented short-segment pedicle screw fixation (PSPVP) versus transpedicular intracorporeal bone grafting + pedicle screw fixation (PSIBG) in the treatment of stage II–III Kummell’s disease. METHODS:A total of 69 patients admitted between November 2017 and March 2021 were included in this study; 36 of these were treated with PSPVP, and 33 were treated with PSIBG. Patients in the two groups were compared in terms of perioperative, follow-up, and imaging data. RESULTS:No statistically significant differences were found between the two groups in terms of operation duration (P > 0.05). However, the PSPVP group was superior to the PSIBG group in terms of incision length, intraoperative blood loss, and length of stay (P  0.05). There were also no statistically significant differences in the VAS score, ODI index, kyphosis Cobb angle, and wedge angle of the affected vertebra between the two groups at corresponding time points (P > 0.05). The heights of the anterior and posterior vertebral margins in the PSIBG group were better than those in the PSPVP group after surgery and at the last follow-up (P < 0.05). In the PSPVP group, a pedicle screw fracture occurred in one patient two months after surgery, while an upper adjacent vertebral fracture occurred in one patient eight months after surgery. CONCLUSION:Both PSPVP and PSIBG can achieve good early clinical efficacy in the treatment of stage II–III Kummell’s disease, with PSPVP being relatively less invasive while producing a poorer orthopedic effect and more complications than PSIBG.

BACKGROUND:Implantable devices such as ventricular assist devices provide appropriate treatment for patients with advanced heart failure. Unfortunately these devices still have many problems, particularly related to blood damage. OBJECTIVE:The aim of this research is to examine two new ventricularassist devices in terms of induced shear stress, exposure time, and induced hemolysis. METHOD:Reverse engineering was used on multiple axial flow ventricular assist devices to collect all the details related to the designs (diameters, lengths, blade angles…), which were used to build two prototypes: Model A and Model B. RESULTS:The obtained results were close to a large extent, except for static pressure rise, where the difference was clear. CONCLUSION:Compared with what has been published in other studies, the overall performance of both models was excellent.

BACKGROUND:During gait, healthy knee coronal kinematics of each bony axis and lower extremity alignment are important because they could be useful as reference data for several surgeries and provide clarification of the etiology of diseases around the knee in healthy participants; however, it remains unknown. OBJECTIVE:The objective of this study was to clarify the kinematics of lower extremity alignment and the bony axes relative to the ground during gait, focused on the coronal plane, in healthy individuals by applying our unique three-dimensional (3D) motion analysis. METHODS:The study included 21 healthy individuals, including 9 healthy females and 12 healthy males with an average age of 36 ± 17 years. Knee kinematics were calculated in a gait analysis by combining the data from a motion-capture system and a 3D lower-extremity alignment assessment system on biplanar long-leg radiographs by using a 3D-2D registration technique. The main kinematic parameters were the dynamic position change relative to the ground, applying the femoral anatomical axis (FAA), tibial anatomical axis (TAA), and dynamic alignment in the coronal plane during the stance phase of gait. RESULTS:The average changes in FAA, TAA, and dynamic varus alignment were 3.7° ± 1.2°, 3.5° ± 0.8°, and 3.0° ± 1.2°, respectively. The TAA tilted laterally during the loading response and a plateau area appeared afterwards; the FAA gradually inclined laterally until the terminal stance phase, and the dynamic alignment showed varus angular change during the loading response. CONCLUSIONS:The tibia and femur were found to change approximately 2–5° of the position of the bony axes relative to the ground. In terms of clinical relevance, our findings can be used to clarify the etiology of diseases around the knee joint and as reference data for surgeries.

BACKGROUND:Biomaterials must allow revascularization for a successful tissue regeneration process. Biomaterials formulated from the extracellular matrix (ECM) have gained popularity in tissue engineering because of their superior biocompatibility, and due to their rheological properties, ECM-hydrogels can be easily applied in damaged areas, allowing cell colonization and integration into the host tissue. Porcine urinary bladder ECM (pUBM) retains functional signaling and structural proteins, being an excellent option in regenerative medicine. Even some small molecules, such as the antimicrobial cathelicidin-derived LL-37 peptide have proven angiogenic properties. OBJECTIVE:The objective of this study was to evaluate the biocompatibility and angiogenic potential of an ECM-hydrogel derived from the porcine urinary bladder (pUBMh) biofunctionalized with the LL-37 peptide (pUBMh/LL37). METHODS:Macrophages, fibroblasts, and adipose tissue-derived mesenchymal stem cells (AD-MSC) were exposed pUBMh/LL37, and the effect on cell proliferation was evaluated by MTT assay, cytotoxicity by quantification of lactate dehydrogenase release and the Live/Dead Cell Imaging assays. Moreover, macrophage production of IL-6, IL-10, IL-12p70, MCP-1, INF-γ, and TNF-α cytokines was quantified using a bead-based cytometric array. pUBMh/LL37 was implanted directly by dorsal subcutaneous injection in Wistar rats for 24 h to evaluate biocompatibility, and pUBMh/LL37-loaded angioreactors were implanted for 21 days for evaluation of angiogenesis. RESULTS:We found that pUBMh/LL37 did not affect cell proliferation and is cytocompatible to all tested cell lines but induces the production of TNF-α and MCP-1 in macrophages. In vivo, this ECM-hydrogel induces fibroblast-like cell recruitment within the material, without tissue damage or inflammation at 48 h. Interestingly, tissue remodeling with vasculature inside angioreactors was seen at 21 days. CONCLUSIONS:Our results showed that pUBMh/LL37 is cytologically compatible, and induces angiogenesis in vivo, showing potential for tissue regeneration therapies.