Subcutaneous Implantation In Rats Research Articles

Reduced Graphene Oxide-Substituted Nanohydroxyapatite: Rejuvenating Bone-Nerve Crosstalk with Electrical Cues in a Fragility Fracture Rat Model under Hyperglycemia.

Diabetes has currently acquired the status of epidemic worldwide, and among its various pathological consequences like retinopathy and nephropathy, bone fragility fractures from diabetic osteopathy occurs in later stages and is equally destructive. Chronic hyperglycemia culminates into deteriorating microvasculature and quality of bone, making it prone to fractures. Among these, hip fractures are most common, especially in older diabetic patients apart from underlying neuropathy. Our study is an attempt to ameliorate hip fragility fracture and nerve trauma with electrical stimulation as an interface in a chronic diabetic rat model. We have fabricated reduced graphene oxide-substituted hydroxyapatite as an electroactive bone substitute and incorporated it into chitosan gelatin cryogels. The in situ reduction of graphene oxide during sintering of hydroxyapatite imparts higher potential to the fabricated composite in dealing with problem at question. The cryogels depicted optimum in vitro biocompatibility and enhanced mineralization after ectopic subcutaneous implantation in rats. The therapeutic potency of composite cryogels was evaluated in a hip fracture model with compression to the sciatic nerve in diabetic rats, mimicking the severe clinical trauma. The presence of cryogels in the femoral neck canal coupled with electrical stimulation and biochemical factors significantly improved bone regeneration in diabetic rats as depicted with microcomputed tomography analysis and histology images. The application of electrical stimulation also ameliorated the nerve trauma observed with 70% improvement in electrophysiological parameters such as the compound muscle action potential with combinatorial therapy. We therefore report the successful implication of a multitarget therapy in a chronic diabetic rat model unraveling the bone-nerve crosstalk with electroactive smart cryogels.

Folic acid modified silver nanoparticles promote endothelialization and inhibit calcification of decellularized heart valves by immunomodulation with anti-bacteria property

Xenogeneic decellularized heart valves (DHVs) have become one of the most commonly used scaffolds for tissue engineered heart valves (TEHVs) due to extensive resources and possessing the distinct three-layer structure similar to native heart valves. However, DHVs as scaffolds face the shortages such as poor mechanical properties, proneness to thrombosis and calcification, difficulty in endothelialization and chronic inflammatory responses etc., which limit their applications in clinic. In this work, we constructed a novel TEHV with immunomodulatory functions by loading folic acid modified silver nanoparticles (FS NPs) on DHVs to overcome these issues. The FS NPs preferentially targeted M1 macrophages and reduced their intracellular H2O2 level, resulting in polarizing them into M2 phenotype. The increased M2 macrophages facilitated to eliminate inflammation, recruit endothelial cells, and promote their proliferation and endothelialization by secreting relative factors. We founded that FS NPs with the size of 80 nm modified DHVs (FSD-80) performed optimally on cytocompatibility and regulating macrophage phenotype ability in vitro. In addition, the FSD-80 had excellent mechanical properties, hemocompatibility and anti-bacteria property. The results of the subcutaneous implantation in rats revealed that the FSD-80 also had good performance in regulating macrophage phenotype, promoting endothelialization, remolding the extracellular matrix and anti-calcification in vivo. Therefore, FS NPs-loaded DHVs possess immunomodulatory functions, which is a feasible and promising strategy for constructing TEHVs with excellent comprehensive performance.

Biocompatibility and Bone Regeneration by Shape Memory Polymer Scaffolds.

Biodegradable, shape memory polymer (SMP) scaffolds based on poly(ε-caprolactone) (PCL) offer unique advantages as a regenerative treatment strategy for critical-sized bone defects. In particular, a conformal fit may be achieved following exposure to warm saline, thereby improving osseointegration and regeneration. Advancing the clinical translation of these SMP scaffolds requires establishment of efficacy not only in non-loading models, but also load-bearing or load-sharing models. Thus, the present study evaluated the biocompatibility and bone regeneration potential of SMP scaffolds in a rabbit distal femoral condyle model. Two distinct SMP scaffold compositions were evaluated, a "PCL-only" scaffold formed from PCL-diacrylate (PCL-DA) and a semi-interpenetrating network (semi-IPN) formed from PCL-DA and poly(L-lactic acid) (PCL:PLLA). Semi-IPN PCL:PLLA scaffolds possess greater rigidity and faster rates of degradation versus PCL scaffolds. In vivo biocompatibility was assessed with a rat subcutaneous implantation model, whereas osseointegration was assessed with a 4 mm × 8 mm rabbit distal femoral condyle defect model. Both types of SMP scaffolds exhibited excellent biocompatibility marked by infiltration with fibrous tissue and a minimal inflammatory response. When implanted in the rabbit distal femur, both SMP scaffolds supported bone ingrowth. Collectively, these results demonstrate that the SMP scaffolds are biocompatible and integrate with adjacent host osseous tissues when implanted in vivo in a load-sharing environment. This study provides key proof-of-concept data necessary to proceed with large animal translational studies and clinical trials in human subjects.

A facile nanopattern modification of silk fibroin electrospun scaffold and corresponding impact on cell proliferation and osteogenesis

Abstract As a well-known natural protein biomaterial, silk fibroin (SF) has shown broad application prospects in typical biomedical fields. However, the mostly used SF from Bombyx mori silkworm lacks specific cell adhesion sites and other bioactive peptide sequences, and there is still significant room for further improvement of their biological functions. Therefore, it is crucial to develop a facile and effective modification strategy for this widely researched biomaterial. In this study, the SF electrospun scaffold has been chosen as a typical SF biomaterial, and air plasma etching has been adopted as a facile nanopattern modification strategy to promote its biological functions. Results demonstrated that the plasma etching could feasibly and effectively create nano-island-like patterns on the complex surface of SF scaffolds, and the detailed nanopattern features could be easily regulated by adjusting the etching time. In addition, the mesenchymal stem cell responses have illustrated that the nanopattern modification could significantly regulate corresponding cell behaviors. Compared with the non-etched scaffold, the 10 min-etched scaffold (10E scaffold) significantly promoted stem cell proliferation and osteogenic differentiation. Moreover, 10E scaffold has also been confirmed to effectively accelerate vascularization and ectopic osteogenesis in vivo using a rat subcutaneous implantation model. However, the mentioned promoting effects would be weakened or even counteracted with the increase of etching time. In conclusion, this facile modification strategy demonstrated great application potential for promoting cell proliferation and differentiation. Thus, it provided useful guidance to develop excellent SF-based scaffolds suitable for bone and other tissue engineering.

A Nontoxic and Biocompatible Method for Augmenting Mechanical Strength of Acellular Matrix by Silk Fibroin Impregnation.

Biological scaffolds are plagued by poor biomechanical properties and untimely degradation. These limitations have yet to be addressed without compromising their biocompatibility. It is desirable to avoid inflammation and have degradation with concomitant host collagen deposition or even site-appropriate in situ regeneration for the successful outcome of an implanted biological scaffold. This work aims to achieve this by utilizing a biocompatible method to modify acellular scaffolds by impregnating alkaline-catalyzed citric acid (CA) cross-linking between the extracellular matrix proteins and silk fibroin (SF)/SF-gelatin (SFG) blends. Combinatorial detergent decellularization was employed to prepare a decellularized porcine liver scaffold (DPL). After proving the decellularization efficiency, the scaffold underwent modification by vacuum impregnation with CA containing SF (SF100DPL) and SFG blends (SFG5050DPL and SFG3070DPL) following pre-cross-linking, drying, and post-cross-linking. The subsequent strength augmentation was demonstrated by significant improvement in tensile strength from 2.4 ± 0.4 MPa (DPL) to, 3.8 ± 0.7 MPa (SF100DPL), 3.4 ± 0.7 MPa (SFG5050DPL), and 3.5 ± 0.2 MPa (SFG3070DPL); Young's modulus from 8.7 ± 1.8 MPa (DPL) to 20 ± 1.9 MPa (SF100DPL), 13.3 ± 2.6 MPa (SFG5050DPL), and 16 ± 1.2 MPa (SFG3070DPL); and suture retention strength from 0.9 ± 0.08 MPa (DPL) to 2.3 ± 0.2 MPa (SF100DPL), 2.8 ± 1.2 MPa (SFG5050DPL), and 2.6 ± 0.9 MPa (SFG3070DPL). The degradation resistance of the modified scaffolds was also markedly improved. Being cytocompatible, its ability to incite tolerable inflammatory and immune responses was confirmed by rat subcutaneous implantation for 14, 30, and 90 days, in terms of inflammatory cell infiltration, neoangiogenesis, and in vitro cytokine release to assess B-cell and T-cell activation. Such ECM composite scaffolds with appropriate strength and biocompatibility offer great promise in soft tissue repair applications such as skin grafting.

Gd Added Mg Alloy for Biodegradable Implant Applications.

Microstructure, mechanical, in vitro and in vivo behavior of extruded Mg alloys with varying Zn/Gd ratios, Mg-2Gd-2Zn-0.5Zr (Zn/Gd = 1), Mg-2Gd-6Zn-0.5Zr (Zn/Gd = 3), and Mg-10Gd-1Zn-0.5Zr (Zn/Gd = 0.1) were investigated. The results revealed that the major secondary phases such as W (Mg3Zn3Gd2), (Mg,Zn)3Gd, LPSO (Long period stacking order) and I (Mg3Zn6Gd) phase in alloys depended on Zn/Gd ratio. These second phases influenced the mechanical as well as biological characteristics of the alloys. Among studied alloys, Mg-10Gd-1Zn-0.5Zr alloy showed the highest yield strength and tensile strength of 270 (±9.29) and 330 MPa (±15.8), respectively, with a reasonably good elongation of 12% (±2.36). The presence of Gd2O3 in the degradation film of Mg-10Gd-1Zn-0.5Zr enhanced the resistance offered by the film, which resulted in its lowest biodegradation, better viability, and cell proliferation under in vitro condition. The short term (subcutaneous implantation in rats for 1 month) in vivo studies showed that the alloy Mg-10Gd-1Zn-0.5Zr degraded at a rate of 0.35 mm/y (±0.02) and did not induce any toxicity to the vital organs.

A controlled release antibiotic wound protectant gel formulated for use in austere environments.

Battlefield wounds are at high risk of infection due to gross contamination and delays in evacuation from forward-deployed locations. The aim of this study was to formulate an antibiotic wound gel for application by a field medic in austere environments to protect traumatic wounds from infection during transport. Formulation development was conducted over multiple phases to meet temperature, handling, in vitro elution, and in vivo tissue response requirements. Thermal properties were evaluated by vial inversion, DSC, and syringe expression force in a temperature range of 4-49°C. Handling was evaluated by spreading onto blood-contaminated tissue and irrigation resistance. Controlled antibiotic release was evaluated by a modified USP immersion cell dissolution method. Local tissue effects were evaluated in vivo by subcutaneous implantation in rats for 7 and 28 days. An oleogel composition of cholesterol, hydrogenated castor oil, soybean oil, and glyceryl monocaprylocaprate met the target performance criteria. Peak expression force from a 5 mL syringe at 4°C was 48.3 N, the dropping point temperature was 68°C, and the oleogel formulation could be spread onto blood-contaminated tissue and resisted aqueous irrigation. The formulation demonstrated sustained release of tobramycin in PBS at 32°C for 5 days. Implantation in a rat dorsal pocket demonstrated a slight tissue reaction after 7 days with minimal to no reaction after 28 days, comparable to a commercial hemostat control. Material resorption was evident after 28 days. The formulation met target characteristics and is appropriate for further evaluation in a large animal contaminated blast wound model.

Novel Flowable Hemostatic Agent ActiClot: Efficacy and Safety Assessment in Rat and Porcine Models.

Background/Objectives: This study evaluated the hemostatic performance and safety of ActiClot (ATC), a new flowable hemostatic agent, through in vivo tests. Methods: ATC was compared with the commercially available FLOSEAL®. ATC consists of carboxymethyl starch, thrombin, and sorbitol powders in Syringe I, and a calcium chloride solution in Syringe II. In vivo evaluation used rat liver bleeding and porcine heart bleeding models. Safety was assessed using a rat subcutaneous implantation model. Results: ATC significantly reduced hemostasis time (70.00 ± 7.35 s) compared to gauze control (240.63 ± 32.31 s) in the rat liver model, showing a 70% reduction. There was no significant difference between ATC and FLOSEAL® (58.75 ± 13.42 s). In the porcine heart model, both agents achieved 100% hemostasis within 3 min, with no significant difference in success rates within 2 min (ATC 87.5%, FLOSEAL® 75%). The gauze control group failed in all tests. The rat subcutaneous implantation model showed no visual ATC observation after 48 h, indicating biocompatibility, with no inflammation observed. Conclusions: ATC demonstrated effective hemostatic performance similar to FLOSEAL® in two in vivo models, with faster hemostasis in the rat liver model. It also showed excellent safety and biocompatibility, indicating its potential for surgical and emergency bleeding control.

Assessing Biocompatibility of Composite Cements by Peri/Intramuscular and Subcutaneous Implantation in Rats.

This study's goal was to evaluate the biocompatibility of two composite cements over a 90-day period by analyzing the individuals' behavior as well as conducting macroscopic and histological examinations and Computed Tomography (CT) scans. We conducted the cytotoxicity test by placing the materials subcutaneously and peri/intramuscularly. Days 30 and 90 were crucial for our research. On those days, we harvested the implants, kidneys and liver to search for any toxic deposits. The biomaterial's uniformity, color and texture remained unaltered despite being in intimate contact with the tissue. Although a slight inflammatory response was observed in the placement location, we observed an improved outcome of the interaction between the material and its insertion area. There were no notable discoveries in the liver and kidneys. According to the obtained results, the biomaterials did not produce any clinical changes nor specific irritation during the research, demonstrating that they are biocompatible with biological tissues.

Antibacterial Iodine-Releasing Coatings of Cross-Linked Poly(N-vinylpyrrolidone) Synthesized by Solvent-Free Initiated Chemical Vapor Deposition.

Biomaterial-associated infections caused by bacteria pose a great threat to human health, and therefore, various antibacterial coatings have been developed to control bacterial infections. Povidone iodine (PVP-I) is a broad-spectrum antimicrobial agent without drug resistance to most pathogenic microorganisms and has been widely used in the clinic. However, its applications in the field of coatings are limited due to its strong water solubility. Here, we used initiated Chemical Vapor Deposition (iCVD) technique to synthesize cross-linked poly(N-vinylpyrrolidone-co-ethylene glycol dimethacrylate) (PVE) coatings to firmly immobilize poly(N-vinylpyrrolidone) (PVP) on surfaces. After complexation with iodine, PVE-I coatings exhibited potent bacteria-killing and antifouling activities against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus in vitro owing to the antibacterial effect of iodine and the hydrophilicity of VP, respectively. The killing and antifouling effects were positively correlated with the VP content. The PVE-I-2 coating displayed excellent anti-infection performance in a rat subcutaneous implantation model in vivo. This study provided a simple method for preparing stable povidone iodine coatings on surfaces via solvent-free iCVD, and combined bacteria-killing and antifouling strategies to fabricate multifunctional antibacterial coatings against bacterial infections on biomaterial surfaces.

Insight the long-term biodegradable Mg-RE-Sr alloy for orthopaedics implant via friction stir processing

Magnesium alloys, noted for their substantial mechanical strength and exceptional biocompatibility, are increasingly being considered for use in biodegradable implants. However, their rapid degradation and significant hydrogen release have limited their applications in orthopaedics. In this study, a novel Mg-RE-Sr alloy was created by friction stir processing to modify its microstructure and enhance its degradation performance. Through microstructural characterization, the friction stir processing effectively refined the grains, accelerated the re-dissolution of precipitates, and ensured a uniform distribution of these phases. The processed alloy demonstrated improved comprehensive properties, with an in vitro corrosion rate of approximately 0.4 mm/y and increases in ultimate tensile strength and elongation by 37 % and 166 %, respectively. Notably, in vivo experiments involving a rat subcutaneous implantation model revealed a slower degradation rate of 0.09 mm/y and a uniform degradation process, basically achieving the requirements for ideal performance in orthopaedic applications. The superior degradation characteristics were attributed to the synergistic effect of attenuated galvanic corrosion and the formation of a dense Y(OH)3/Y2O3 film induced by an exceptional microstructure with a highly solid-soluted matrix and uniformly refined precipitates. Meanwhile, the alloys exhibited excellent biocompatibility and did not cause undesirable inflammation or produce toxic degradation products. These improvements in biocompatibility and degradation characteristics indicate great promise for the use of this friction stir processed alloy in osteosynthesis systems in the clinical setting.

Chondroitin Sulfate Derivative Cross-Linking of Decellularized Heart Valve for the Improvement of Mechanical Properties, Hemocompatibility, and Endothelialization.

Tissue-engineered heart valve (TEHV) has emerged as a prospective alternative to conventional valve prostheses. The decellularized heart valve (DHV) represents a promising TEHV scaffold that preserves the natural three-dimensional structure and retains essential biological activity. However, the limited mechanical strength, fast degradation, poor hemocompatibility, and lack of endothelialization of DHV restrict its clinical use, which is necessary for ensuring its long-term durability. Herein, we used oxidized chondroitin sulfate (ChS), one of the main components of the extracellular matrix with various biological activities, to cross-link DHV to overcome the above problems. In addition, the ChS-adipic dihydrazide was used to react with residual aldehyde groups, thus preventing potential calcification. The results indicated notable enhancements in mechanical properties and resilience against elastase and collagenase degradation in vitro as well as the ability to withstand extended periods of storage without compromising the structural integrity of valve scaffolds. Additionally, the newly cross-linked valves exhibited favorable hemocompatibility in vitro and in vivo, thereby demonstrating exceptional biocompatibility. Furthermore, the scaffolds exhibited traits of gradual degradation and resistance to calcification through a rat subcutaneous implantation model. In the rat abdominal aorta implantation model, the scaffolds demonstrated favorable endothelialization, commendable patency, and a diminished pro-inflammatory response. As a result, the newly constructed DHV scaffold offers a compelling alternative to traditional valve prostheses, which potentially advances the field of TEHV.

Designing a Naturally Inspired Conductive Copolymer to Engineer Wearable Bioadhesives for Sensing Applications.

The design of adhesive and conductive soft hydrogels using biopolymers with tunable mechanical properties has received significant interest in the field of wearable sensors for detecting human motions. These hydrogels are primarily fabricated through the modification of biopolymers to introduce cross-linking sites, the conjugation of adhesive components, and the incorporation of conductive materials into the hydrogel network. The development of a multifunctional copolymer that integrates adhesive and conductive properties within a single polymer chain with suitable cross-linking sites eliminates the need for biopolymer modification and the addition of extra conductive and adhesive components. In this study, we synthesized a copolymer based on poly([2-(methacryloyloxy)ethyl] trimethylammonium chloride-co-dopamine methacrylamide) (p(METAC-DMA)) using a controlled radical polymerization, allowing for the efficient conjugation of both adhesive and conductive units within a single polymer chain. Subsequently, our multifunctional hydrogel named Gel-MD was fabricated by mixing the p(METAC-DMA) copolymer with non-modified gelatin in which cross-linking took place in an oxidative environment. We confirmed the biocompatibility of the Gel-MD hydrogel through in vitro studies using NIH 3T3 cells as well as in vivo subcutaneous implantation in rats. Furthermore, the Gel-MD hydrogel was effective and sensitive in detecting various human motions, making it a promising wearable sensor for health monitoring and diagnosis.

Creating and evaluating a novel small diameter PCL/PU vascular graft for finger reconstruction: A comprehensive analysis of structural, mechanical, in vitro, and in vivo assessments

This study addresses vascular repair challenges during digital replantation by developing an electrospun nanofibrous scaffold using PCL and PU for small-diameter vascular grafts (<2 mm). Structural validation employed diverse techniques such as FE-SEM, DSC, and FTIR analysis, while mechanical properties like stress and strain were rigorously evaluated. Functionality was assessed through in vitro assays and in vivo experiments, including subcutaneous implantation in rats and femoral artery insertion in rabbits. The scaffold demonstrated favorable mechanical properties and enhanced cell attachment, with minimal lumen fibrosis and good blood compatibility observed. Post-implantation in rabbits showed well-established blood flow and signs of tissue formation, suggesting potential for regenerative medicine. In conclusion, the PU85/PCL15 scaffold exhibited promising outcomes, highlighting its potential in microvascular tissue engineering Level of evidenceLevel V

Injectable hyaluronate/collagen hydrogel with enhanced safety and efficacy for facial rejuvenation

Collagen, known for its excellent biocompatibility and biological properties, has limited in vivo maintenance duration after implantation, while hyaluronic acid faces challenges such as various complications and insufficient support for cell proliferation. In this study, an injectable hyaluronic acid/collagen (HCol) hydrogel was developed to achieve enhanced cell-material interactions and accelerated skin regeneration. Physical and chemical characterizations demonstrated that the HCol hydrogel was injectable and stable after the implantation. In vitro cell culture results illustrated that the hydrogel promoted the proliferation of human dermal fibroblasts, extracellular matrix expression and angiogenesis. The subcutaneous implantation in rats showed the superior biocompatibility of HCol hydrogel and enhanced secretion and deposition of extracellular matrix, compared with commercial hyaluronic acid dermal filler. MRI analysis showed that the hydrogel stably remained in vivo for at least three months. The histological examination and SHG signals further demonstrated that the hydrogel modulated fibroblast phenotype and stimulated vascular ingrowth and collagen synthesis, without inducing significant inflammation, swelling or erythema in vivo.Graphical

In vivo characterization of a luffa-based composite scaffold for subcutaneous implantation in rats

Recent advancements in tissue engineering have witnessed luffa-derived scaffolds, exhibiting their exceptional potential in cellular proliferation, biocompatibility, appropriate interconnectivity, and biomechanical strength. In vivo studies involved implanting fabricated scaffolds subcutaneously in Wistar rats to evaluate their impact on the heart, liver, and kidneys. This approach provided a safe and minimally invasive means to evaluate scaffold compatibility with surrounding tissues. Male Wistar rats were categorized into four distinct groups, Group A, B, C, and D are referred to as 3% LC implanted scaffolds, 5% LC implanted scaffolds, control (without luffa scaffolds), and Sham (without any scaffold implantation), respectively. Histological analysis in all the groups indicated that the animal models did not exhibit any signs of inflammation or toxicity, suggesting favorable tissue response to the implanted scaffolds. Initial observations revealed elevated levels of enzymes and biomarkers in the experimental groups after a 24 h interval, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatine kinase-MB (CK-MB), and serum creatinine. However, these parameters normalized 3 weeks post-implantation, with no significant increase compared to the control groups, suggesting that the implanted luffa-based scaffolds did not induce adverse effects on the heart, liver, and kidneys. Furthermore, the scaffold’s significant pore size and porosity enable it to release drugs, including antibacterial medications. This study demonstrates promising results, indicating excellent scaffold porosity, sustained drug release, affirming the in vivo biocompatibility, absence of inflammatory responses, and overall tissue compatibility highlighting the immense potential of these luffa-based scaffolds in various tissue engineering and regenerative medicine applications.

A stretchable, electroconductive tissue adhesive for the treatment of neural injury

AbstractSuccessful nerve repair using bioadhesive hydrogels demands minimizing tissue–material interfacial mechanical mismatch to reduce immune responses and scar tissue formation. Furthermore, it is crucial to maintain the bioelectrical stimulation‐mediated cell‐signaling mechanism to overcome communication barriers within injured nerve tissues. Therefore, engineering bioadhesives for neural tissue regeneration necessitates the integration of electroconductive properties with tissue‐like biomechanics. In this study, we propose a stretchable bioadhesive based on a custom‐designed chemically modified elastin‐like polypeptides (ELPs) and a choline‐based bioionic liquid (Bio‐IL), providing an electroconductive microenvironment to reconnect damaged nerve tissue. The stretchability akin to native neural tissue was achieved by incorporating hydrophobic ELP pockets, and a robust tissue adhesion was obtained due to multi‐mode tissue–material interactions through covalent and noncovalent bonding at the tissue interface. Adhesion tests revealed adhesive strength ~10 times higher than commercially available tissue adhesive, Evicel®. Furthermore, the engineered hydrogel supported in vitro viability and proliferation of human glial cells. We also evaluated the biodegradability and biocompatibility of the engineered bioadhesive in vivo using a rat subcutaneous implantation model, which demonstrated facile tissue infiltration and minimal immune response. The outlined functionalities empower the engineered elastic and electroconductive adhesive hydrogel to effectively enable sutureless surgical sealing of neural injuries and promote tissue regeneration.

The treatment efficacy of bone tissue engineering strategy for repairing segmental bone defects under diabetic condition.

Diabetes mellitus is a systematic disease which exert detrimental effect on bone tissue. The repair and reconstruction of bone defects in diabetic patients still remain a major clinical challenge. This study aims to investigate the potential of bone tissue engineering approach to improve bone regeneration under diabetic condition. In the present study, decalcified bone matrix (DBM) scaffolds were seeded with allogenic fetal bone marrow-derived mesenchymal stem cells (BMSCs) and cultured in osteogenic induction medium to fabricate BMSC/DBM constructs. Then the BMSC/DBM constructs were implanted in both subcutaneous pouches and large femoral bone defects in diabetic (BMSC/DBM in DM group) and non-diabetic rats (BMSC/DBM in non-DM group), cell-free DBM scaffolds were implanted in diabetic rats to serve as the control group (DBM in DM group). X-ray, micro-CT and histological analyses were carried out to evaluate the bone regenerative potential of BMSC/DBM constructs under diabetic condition. In the rat subcutaneous implantation model, quantitative micro-CT analysis demonstrated that BMSC/DBM in DM group showed impaired bone regeneration activity compared with the BMSC/DBM in non-DM group (bone volume: 46 ± 4.4mm3 vs 58.9 ± 7.15mm3, *p < 0.05). In the rat femoral defect model, X-ray examination demonstrated that bone union was delayed in BMSC/DBM in DM group compared with BMSC/DBM in non-DM group. However, quantitative micro-CT analysis showed that after 6months of implantation, there was no significant difference in bone volume and bone density between the BMSC/DBM in DM group (199 ± 63mm3 and 593 ± 65mg HA/ccm) and the BMSC/DBM in non-DM group (211 ± 39mm3 and 608 ± 53mg HA/ccm). Our data suggested that BMSC/DBM constructs could repair large bone defects in diabetic rats, but with delayed healing process compared with non-diabetic rats. Our study suggest that biomaterial sacffolds seeded with allogenic fetal BMSCs represent a promising strategy to induce and improve bone regeneration under diabetic condition.

Core/shell nanofibrous conduit containing natural surfactant enhanced axonal regrowth guiding for peripheral nerve regeneration

This study illustrated the impact of Saponins in electrospun nanofibers on nerve regeneration and compared them with Tween 80, which is commonly used as a synthetic surfactant. The study explores the effect of Saponins, natural emulsifiers known for their effectiveness in forming and stabilizing emulsions. Surfactant choice is crucial due to its effects on fluid stability, influenced by parameters like polymer concentration, homogenization rate, and surfactant type/amount. This study explored PCL as the core and PVA as the shell.Core/shell scaffolds displayed favorable wettability (contact angle: 67.0° ± 1.3) and improved mechanical properties (wet state tensile strength: PVA 1.1 ± 0.2 MPa, PVA/PCL-Saponin 2.0 ± 0.5 MPa). The MTT viability assay demonstrated higher viability of PC12 cells on Saponin-containing nanofibers (85.0 % ± 0.1) compared to Tween 80 (69.0 % ± 0.1) after 24 h. Subcutaneous implantation in rats showed no significant inflammation after one week. Eventually, in the animal model, the conduit containing Saponin was more effective than Tween 80 in repairing the rat's sciatic nerve within six weeks, as evidenced by NF-200 counts and histological studies. Overall, the study indicates that PVA/PCL-Saponin nanofibers, without requiring Saponin surfactant removal, show high quality and effectiveness for tissue engineering and medical purposes.

Mechanically resilient hybrid aerogels containing fibers of dual-scale sizes and knotty networks for tissue regeneration.

The structure and design flexibility of aerogels make them promising for soft tissue engineering, though they tend to come with brittleness and low elasticity. While increasing crosslinking density may improve mechanics, it also imparts brittleness. In soft tissue engineering, resilience against mechanical loads from mobile tissues is paramount. We report a hybrid aerogel that consists of self-reinforcing networks of micro- and nanofibers. Nanofiber segments physically entangle microfiber pillars, allowing efficient stress distribution through the intertwined fiber networks. We show that optimized hybrid aerogels have high specific tensile moduli (~1961.3 MPa cm3 g-1) and fracture energies (~7448.8 J m-2), while exhibiting super-elastic properties with rapid shape recovery (~1.8 s). We demonstrate that these aerogels induce rapid tissue ingrowth, extracellular matrix deposition, and neovascularization after subcutaneous implants in rats. Furthermore, we can apply them for engineering soft tissues via minimally invasive procedures, and hybrid aerogels can extend their versatility to become magnetically responsive or electrically conductive, enabling pressure sensing and actuation.