Macrophage Polarization Modulated by NF-κB in Polylactide Membranes-Treated Peritendinous Adhesion.

Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.

Mechano-Informed Biomimetic Polymer Scaffolds by Incorporating Self-Powered Zinc Oxide Nanogenerators Enhance Motor Recovery and Neural Function.

Piezoelectric materials can produce electrical power from the mechanical stimulation and thus, they may accelerate electroactive tissue healing as a promising treatment for traumatic peripheral nerve injuries. In this study, a piezoelectric zinc oxide nanogenerator scaffold is manufactured by 3D injectable multilayer biofabrication. The piezoelectric polymeric scaffold displays desirable mechanical and physical characteristics, such as aligned porosity, high elasticity, scaffold stiffness, surface energy, and excellent shear behavior. In addition, its biocompatibility supplies Schwann cells with an adhesive, proliferative, and angiogenic interface, as is reflected by higher expression of functional proteins including nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). In vivo mechanical stimuli by treadmill practice contribute to the comprehensive reparative therapy. The piezoelectric conduit accelerates nerve conducting velocity, promotes axonal remyelination, and restores motor function by recovering endplate muscles. Moreover, the piezoelectric nanogenerator scaffold creates biomimetic electrically conductive microenvironment without causing noticeable toxicity to functioning organs and improves peripheral nerve restoration by the multifunctional characteristics. Therefore, the mechano-informed biomimetic piezoelectric scaffold may have enormous potential in the neuroengineering for regenerative medicine.

3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration.

Peripheral nerve defect is a common and severe kind of injury in traumatic accidents. Melatonin can improve peripheral nerve recovery by inhibiting oxidative stress and inflammation after traumatic insults. In addition, it triggers autophagy pathways to increase regenerated nerve proliferation and to reduce apoptosis. In this study, we fabricated a melatonin-controlled-release scaffold to cure long-range nerve defects for the first time. 3D manufacture of melatonin/polycaprolactone nerve guide conduit increased Schwann cell proliferation and neural expression in vitro and promoted functional, electrophysiological and morphological nerve regeneration in vivo. Melatonin nerve guide conduit ameliorated immune milieu by reducing oxidative stress, inflammation and mitochondrial dysfunction. In addition, it activated autophagy to restore ideal microenvironment, to provide energy for nerves and to reduce nerve cell apoptosis, thus facilitating nerve debris clearance and neural proliferation. This innovative scaffold will have huge significance in the nerve engineering.

Multi-layer electrospun membrane mimicking tendon sheath for prevention of tendon adhesions.

Defect of the tendon sheath after tendon injury is a main reason for tendon adhesions, but it is a daunting challenge for the biomimetic substitute of the tendon sheath after injury due to its multi-layer membrane-like structure and complex biologic functions. In this study, a multi-layer membrane with celecoxib-loaded poly(l-lactic acid)-polyethylene glycol (PELA) electrospun fibrous membrane as the outer layer, hyaluronic acid (HA) gel as middle layer, and PELA electrospun fibrous membrane as the inner layer was designed. The anti-adhesion efficacy of this multi-layer membrane was compared with a single-layer use in rabbit flexor digitorum profundus tendon model. The surface morphology showed that both PELA fibers and celecoxib-loaded PELA fibers in multi-layer membrane were uniform in size, randomly arrayed, very porous, and smooth without beads. Multi-layer membrane group had fewer peritendinous adhesions and better gliding than the PELA membrane group and control group in gross and histological observation. The similar mechanical characteristic and collagen expression of tendon repair site in the three groups indicated that the multi-layer membrane did not impair tendon healing. Taken together, our results demonstrated that such a biomimetic multi-layer sheath could be used as a potential strategy in clinics for promoting tendon gliding and preventing adhesion without poor tendon healing.

Silver nanoparticles/ibuprofen-loaded poly(L-lactide) fibrous membrane: anti-infection and anti-adhesion effects.

Infection caused by bacteria is one of the crucial risk factors for tendon adhesion formation. Silver nanoparticles (AgNP)-loaded physical barriers were reported to be effective in anti-infection and anti-adhesion. However, high silver load may lead to kidney and liver damages. This study was designed for Ibuprofen (IBU)-loaded poly(L-lactide) (PLLA) electrospun fibrous membranes containing a low dosage of Ag to evaluate its potential in maintaining suitable anti-infection and good anti-adhesion effects. The in vitro drug release study showed a sustained release of Ag ions and IBU from the membrane. Inferior adherence and proliferation of fibroblasts were found on the Ag4%-IBU4%-loaded PLLA electrospun fibrous membranes in comparison with pure PLLA and 4% Ag-loaded PLLA membranes. In the antibacterial test, all Ag-loaded PLLA electrospun fibrous membranes prevented the adhesion of Staphylococcus aureus and Staphylococcus epidermidis. Taken together, these results demonstrate that Ibuprofen is effective in enhancing the anti-adhesion and anti-proliferation effects of 4% Ag-loaded PLLA fibrous membrane. The medical potential of infection reduction and adhesion prevention of Ag4%-IBU4%-loaded PLLA electrospun fibrous membrane deserves to be further studied.

Prevention of intra-abdominal adhesion by bi-layer electrospun membrane.

The aim of this study was to compare the anti-adhesion efficacy of a bi-layer electrospun fibrous membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer with a single-layer PCL electrospun fibrous membrane in a rat cecum abrasion model. The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The bi-layer and PCL membranes were applied between the cecum and the abdominal wall, respectively. Control animals did not receive any treatment. After postoperative day 14, a visual semiquantitative grading scale was used to grade the extent of adhesion. Histological analysis was performed to reveal the features of adhesion tissues. Bi-layer membrane treated animals showed significantly lower adhesion scores than control animals (p < 0.05) and a lower adhesion score compared with the PCL membrane. Histological analysis of the bi-layer membrane treated rat rarely demonstrated tissue adhesion while that of the PCL membrane treated rat and control rat showed loose and dense adhesion tissues, respectively. Bi-layer membrane can efficiently prevent adhesion formation in abdominal cavity and showed a significantly decreased adhesion tissue formation compared with the control.

Pyrrolidine Dithiocarbamate-loaded Electrospun Membranes for Peritendinous Anti-adhesion through Inhibition of the Nuclear Factor-κB Pathway.

Peritendinous adhesion is a major cause of limb dysfunction and disability in clinical practice. Numerous studies suggest that activation of nuclear factor-κB (NF-κB) pathway in macrophages could be the pivotal figure in excessive collagen synthesis and thus peritendinous adhesion formation. In this study, we assumed this pathological process could be suppressed by inhibiting NF-κB phosphorylation and nuclear translocation using pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor with the ability to penetrate cell membranes, in macrophages. Then, we conducted electrospinning process to incorporate PDTC into poly(L-lactic) acid (PLA) electrospinning membranes, that is, the PDTC-PLA membranes. Further, with integral film quality and stable drug release property, the PDTC-PLA membranes were subsequently analyzed in the capability and mechanism of preventing adhesion formation both in vitro and in vivo. Our results showed inhibition of macrophage proliferation as well as NF-κB pathway activation from in vitro assays and outstanding promotion in inhibiting NF-κB p65 phosphorylation and reducing adhesion formation from in vivo assays of PDTC-PLA compared to PLA membranes. In conclusion, our findings suggested that PDTC-PLA as an alternative therapeutic approach alleviated inflammation and peritendinous adhesion formation through NF-κB signaling pathway. STATEMENT OF SIGNIFICANCE: Pyrrolidine dithiocarbamate (PDTC) can be blended into poly-L-lactic acid (PLA) fibrous membranes by electrospinning process. This incorporation of PDTC into PLA is an effective way to inhibit proinflammatory activation of macrophages and to achieve advanced anti-adhesion outcome after tendon repair.

Biomimetic sheath membrane via electrospinning for antiadhesion of repaired tendon.

The hierarchical architecture and complex biologic functions of native sheath make its biomimetic substitute a daunting challenge. In this study, a biomimetic bilayer sheath membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (HA/PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer was fabricated by a combination of sequential and microgel electrospinning technologies. This material was characterized by mechanical testing and analysis of morphology, surface wettability, and drug release. Results of an in vitro drug release study showed sustained release. The outer layer had fewer cells proliferating on its surface compared to tissue culture plates or the inner layer. In a chicken model, peritendinous adhesions were reduced and tendon gliding were improved by the application of this sheath membrane. Taken together, our results demonstrate that such a biomimetic bilayer sheath can release HA sustainably as well as promoting tendon gliding and preventing adhesion.

Biomimetic multilayer polycaprolactone/sodium alginate hydrogel scaffolds loaded with melatonin facilitate tendon regeneration.

Tendon injury is one of the most common musculoskeletal diseases in the world, severely challenging the public health care system. Electrospinning technique using polymer materials (i.e. polycaprolactone (PCL)) and hydrogels (i.e. sodium alginate (ALG)) contribute to the development and application of smart composite scaffolds in the tendon tissue engineering by advantageously integrating mechanical properties and biocompatibility. As a potential natural antioxidant, melatonin (MLT) represents the potential to promote tendon repair. Here, we develop an MLT-loaded PCL/ALG composite scaffold that effectively promotes tendon injury repair in vivo and in vitro via a controlled release of MLT, possibly mechanically relying on an antioxidant stress pathway. This biomimetic composite scaffold will be of great significance in the tendon tissue engineering.

Electroactive nanomaterials in the peripheral nerve regeneration.

Severe peripheral nerve injuries are threatening the life quality of human beings. Current clinical treatments contain some limitations and therefore extensive research and efforts are geared towards tissue engineering approaches and development. The biophysical and biochemical characteristics of nanomaterials are highly focused on as critical elements in the design and fabrication of regenerative scaffolds. Recent studies indicate that the electrical properties and nanostructure of biomaterials can significantly affect the progress of nerve repair. More importantly, these studies also demonstrate the fact that electroactive nanomaterials have substantial implications for regulating the viability and fate of primary supporting cells in nerve regeneration. In this review, we summarize the current knowledge of electroconductive and piezoelectric nanomaterials. We exemplify typical cellular responses through cell-material interfaces, and the nanomaterial-induced microenvironment rebalance in terms of several key factors, immune responses, angiogenesis and oxidative stress. This work highlights the mechanism and application of electroactive nanomaterials to the development of regenerative scaffolds for peripheral nerve tissue engineering.

Biological and biocompatible characteristics of fullerenols nanomaterials for tissue engineering.

Fullerenes, as hydrophobic molecules, are limited in biomedical function due to their very low solubility. But taking C60(OH)ₓ as an example, the properties of fullerenols were analyzed. It was found that fullerenols had good stability, water solubility, good biocompatibility and low cytotoxicity by adding a hydroxyl group to carbon atoms. In the biomedical field, it has been found that fullerene C60 can be used as a powerful free radical scavenger, with antioxidant activity, with antibacterial and inhibitory effects on cancer cells. Fullerenols inherit the good properties of fullerenes, and are better used in cancer treatment, including loading drug therapy and directly as an anticancer drug. In addition, fullerenols are also used in the repair of myocardial injury, the treatment of myocardial infarction and neuroprotection. With the development of tissue engineering technology, the preparation of nerve scaffolds which can improve ischemia, hypoxia and oxidative stress after nerve injury has become a research hotspot. The electron absorption and reduction characteristics of fullerenols in biomedical research bring new ideas for the treatment of oxidative stress in the repair of peripheral nerve defects. It seems that the research on fullerenols loaded neural scaffold has great prospects.

The single transoral approach for Os odontoideum with irreducible atlantoaxial dislocation.

We report a 52-year-old female patient with a 2-year history of local neck pain, decreased cervical spine rotation, progressive numbness and weakness of both arms. Preoperative, dynamic X-rays, computed tomography, three-dimensional computed tomography demonstrated a displaced Os odontoideum with irreducible Subluxation of C1/2. We used a single transoral approach release, reduction using an assistance of skull traction, bone fusion and stabilization in the treatment of Os odontoideum with irreducible alantoaxial dislocation. Postoperative, the patient was free of all symptoms and X-rays taken showed a stable fusion of C1/2 at 6th postoperative month. This technique in the treatment of Os odontoideum with irreducible alantoaxial dislocation is atraumatic and effective. And preoperative dynamic X-rays, computed tomography, three-dimensional computed tomography and MRI scans provided an invaluable aid to select this operative procedure.

Beeswax-inspired superhydrophobic electrospun membranes for peritendinous anti-adhesion.

Posttraumatic peritendinous adhesion leads to limb disability. Physical barrier was widely used and thus focus was paid to fabricate the hydrophobic surfaces of electrospun membrane for anti-adhesion. However, current methods are limited and complicated. In this study, beeswax (Wax)/poly-L-lactic acid (PLA) anti-adhesion membranes were fabricated by blending electrospinning of Wax and PLA. The water contact angle was tested to investigate the hydrophobicity of the surfaces. Incorporation of Wax into PLA did not destroy the micro-pores between Wax/PLA fibers. After 7-day culture, proliferation of fibroblasts on Wax/PLA anti-adhesion membranes were significantly less than that on culture dish and PLA membranes. In rat Achilles adhesion model, least histological peritendinous adhesion formation was detected on the repaired sites in the group treated with Wax/PLA membranes than PLA membranes. Consequently, blending electrospinning of Wax into PLA is an easy method to fabricate hydrophobic surface of electrospun membrane with advanced peritendinous anti-adhesion outcome.

(-)-Epigallocatechin gallate-loaded polycaprolactone scaffolds fabricated using a 3D integrated moulding method alleviate immune stress and induce neurogenesis.

OBJECTIVES: In peripheral neuropathy, the underlying mechanisms of nerve and muscle degeneration include chronic inflammation and oxidative stress in fibrotic tissues. (-)-Epigallocatechin gallate (EGCG) is a major, active component in green tea and may scavenge free radical oxygen and attenuate inflammation. Conservative treatments such as steroid injection only deal with early, asymptomatic, peripheral neuropathy. In contrast, neurolysis and nerve conduit implantation work effectively for treating advanced stages. MATERIALS AND METHODS: An EGCG-loaded polycaprolactone (PCL) porous scaffold was fabricated using an integrated moulding method. We evaluated proliferative, oxidative and inflammatory activity of rat Schwann cells (RSCs) and rat skeletal muscle cells (RSMCs) cultured on different scaffolds in vitro. In a rat radiation injury model, we assessed the morphological, electrophysiological and functional performance of regenerated sciatic nerves and gastrocnemius muscles, as well as oxidative stress and inflammation state. RESULTS: RSCs and RSMCs exhibited higher proliferative, anti-oxidant and anti-inflammatory states in an EGCG/PCL scaffold. In vivo studies showed improved nerve and muscle recovery in the EGCG/PCL group, with increased nerve myelination and muscle fibre proliferation and reduced macrophage infiltration, lipid peroxidation, inflammation and oxidative stress indicators. CONCLUSIONS: The EGCG-modified PCL porous nerve scaffold alleviates cellular oxidative stress and repairs peripheral nerve and muscle structure in rats. It attenuates oxidative stress and inflammation in vivo and may provide further insights into peripheral nerve repair in the future.

A comparative study of internal fixation and prosthesis replacement for radial head fractures of Mason type III.

Although several treatment options for radial head fractures are available, no clear solutions exist. In this study we therefore compare open reduction and internal fixation (ORIF) with bipolar radial head prosthesis replacement in treatment of radial head fractures of Mason type III. Cement stem and bipolar radial prosthesis were used to treat 12 fresh cases and two old cases of Mason type III radial head fracture. As a control group, another eight cases of radial head type III fracture were treated with ORIF with cannulated screws and Kirschner (K) wires. The 14 patients who received radial head prosthesis replacement were followed-up for 15.9 months (range 10-27 months). According to elbow functional evaluation criteria by Broberg and Morrey, we found excellent results in nine cases, good in four, and fair in one. Mean follow-up of the eight cases in the ORIF group was 14 months (range 10-21 months), with good results in one case, fair in four, and poor in three. The result was good or excellent in 92.9% of prosthesis replacement patients and in 12.5% of ORIF patients. This difference is statistically significant (P = 0.0004; Fisher's exact test). We concluded that bipolar radial head prosthesis replacement is better than ORIF in treatment of Mason type III radial head fracture.

Macrophage infiltration of electrospun polyester fibers.

Electrospun fibrous polylactide (PLA) membranes have been widely used for peritendinous anti-adhesion, but their degradation may lead to granuloma formation triggered by macrophages as the result of a foreign body reaction. To understand and solve this problem in peritendinous anti-adhesion, the effects of electrospun fibrous PLA membranes (PLA-M) and the mechanism by which macrophages elicit a foreign body reaction should be elaborated. Thus, the purpose of this study was to evaluate the ability of PLA-M and ibuprofen (IBU)-loaded fibrous PLA membranes (IBU/PLA-M) to prevent adhesion/granuloma formation around the tendon, and to understand the mechanism of macrophage infiltration. The results showed that PLA-M and IBU/PLA-M were porous and that IBU could be sustainably released from IBU/PLA-M. The adhesion and proliferation of RAW264.7 macrophages were worse on the surface of IBU/PLA-M than on PLA-M. After implantation around the tendon, IBU/PLA-M had higher anti-adhesion and tendon healing scores than PLA-M. Furthermore, PLA-M was able to promote macrophage infiltration, neovascularization, TNF-α expression and collagen III deposition to a greater extent than IBU/PLA-M. Consequently, these results show that macrophages can be triggered by PLA-M which subsequently leads to inflammation and granuloma formation, while IBU/PLA-M results in enhanced anti-inflammation and anti-adhesion effects when compared to PLA-M, by reducing macrophage infiltration.

Electrospun fibrous membranes featuring sustained release of ibuprofen reduce adhesion and improve neurological function following lumbar laminectomy.

Electrospun fibrous membranes provide suitable physical anti-adhesion barriers for reducing tissue anti-adhesion following surgery. However, often during the biodegradation process, these barriers trigger inflammation and cause a foreign body reaction with subsequent decrease in anti-adhesion efficacy. Here, a facile strategy comprising the incorporation of ibuprofen (IBU) into implantable membranes and its sustained release was proposed in order to improve anti-adhesion effects and neurological outcomes, namely to prevent failed back surgery syndrome (FBSS). The combination of free IBU and a newly synthetized polymeric prodrug of IBU, namely poly(hydroxyethyl methacrylate) with ester-linked IBU, was successfully used in order to reduce initial burst drug release and provide sustained drug release from fibrous membranes throughout several weeks. Such release profile was shown useful in preventing both acute and chronic inflammation in rats following laminectomy and membrane implantation. Moreover, histological analysis provided evidence of an excellent anti-adhesion effect, while associated neurological deficits were effectively reduced. Furthermore, the assessment of macrophage density, neovascularization, and related gene expression at the lesion site revealed that a sustained anti-inflammatory effect was achieved with the IBU-loaded proposed fibrous membranes. Results suggested that the COX2 pathway plays an important role in the development epidural fibrosis and arachnoiditis. Overall, this study provided evidence that precisely engineered IBU-loaded electrospun fibrous membranes may be useful in preventing FBSS and able to potentially impact the outcome of patients undergoing spine surgery.

[Improvement of blood compatibility of small intestinal submucosa used as engineering vascular scaffolds by nano-bionic surface modification].

OBJECTIVE: To investigate the effects of nano-bionic surface modification in improving the blood compatibility of small intestinal submucosa (SIS) used as engineering vascular scaffolds. METHODS: SIS films were obtained from pig and underwent nano-bionic surface modification with plasma initiation technique. Scanning electron microscopy (SEM) was used to observe the morphological features, including water contact angle, of the SIS films after nano-bionic surface modification. Modified SIS films were immersed into human platelet-rich plasma for 10 s and then observed for the adhesion of platelet on the surface thereof. Another modified SIS films were immersed into anticoagulant human blood to test the prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). Twenty dogs were randomly divided into 2 equal groups to undergo cutting of bilateral femoral arteries and anastomosis with tube-like scaffolds made of modified or un-modified SIS films. Color Doppler ultrasonography was used to examine the blood flow 1, 3, and 6 weeks after operation. The dogs were killed in batches 2 and 6 weeks after operation to take out the SIS vessels to observe the existence of mural thrombus and undergo microscopy. RESULTS: SEM showed island-like and groove-like surface morphology in the modified SIS films, and the water contact angle decreased from 105.3 degrees to 62.0 degrees. After treatment by anticoagulant human blood the PT, APTT, and TT of the modified SIS films increased from 30.5 s, 9.8 s, and 13.6 s to 81.5 s, 39.6 s, and 50.2 s respectively. SEM showed that the number of adhering platelets was less on the surface of the modified SIS films than on the surface of un-modified SIS films. Animal experiment showed that 4 blood vessels anastomosed with un-modified SIS tube became completely thrombosed within 3 hours, and the other 6 became completely thrombosed 3 days later, and the 10 blood vessels anastomosed with modified SIS tube remained patent till 6 weeks after operation. Gross observation showed that the implanted scaffolds made of modified SIS films had become biological tube-like 2 weeks after operation, and became integrated tubes with their inner walls covered with endothelial cells 6 weeks post-operatively. CONCLUSION: Nano-bionic surface modified SIS film possesses good and persistent antithrombogenicity and shows excellent blood compatibility.

Release of celecoxib from a bi-layer biomimetic tendon sheath to prevent tissue adhesion.

Posttraumatic tendon adhesion limits the motion of the limbs greatly. Biomimetic tendon sheaths have been developed to promote tendon healing and gliding. However, after introduction of these biomaterials, the associated inflammatory responses can decrease the anti-adhesion effect. Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) that can decrease inflammation responses. We blended hyaluronic acid and poly(l-lactic acid)-polyethylene glycol (PELA) with microgel electrospinning technology to form an inner layer of a bi-layer biomimetic sheath using sequential electrospinning of an outer celecoxib-PELA layer. Electrospun bi-layer fibrous membranes were mechanically tested and characterized by morphology, surface wettability, and drug release. The tensile strength showed a decreased trend and water contact angles were 114.7 ± 3.9°, 103.6 ± 4.4°, 116.3 ± 5.1°, 122.8 ± 4.7°, and 126.5 ± 4.2° for the surface of PELA, hyaluronic acid-PELA, 2, 6, and 10% celecoxib-PELA electrospun fibrous membranes, respectively. In vitro drug release studies confirmed burst release and then sustained release from the fibrous membranes containing celecoxib for 20 days. In a chicken model of flexor digitorum profundus tendon surgery, the outer celecoxib/PELA layer offered advanced anti-adhesion roles compared to the outer PELA layer and the inner hyaluronic acid-loaded PELA layer still offered tendon healing and gliding. Thus, celecoxib-loaded anti-adhesive tendon sheaths can continuously offer bi-layer biomimetic tendon sheath effects with celecoxib release from the outer layer to prevent tendon adhesion.

Superabsorbent 3D Scaffold Based on Electrospun Nanofibers for Cartilage Tissue Engineering.

Electrospun nanofibers have been used for various biomedical applications. However, electrospinning commonly produces two-dimensional (2D) membranes, which limits the application of nanofibers for the 3D tissue engineering scaffold. In the present study, a porous 3D scaffold (3DS-1) based on electrospun gelatin/PLA nanofibers has been prepared for cartilage tissue regeneration. To further improve the repairing effect of cartilage, a modified scaffold (3DS-2) cross-linked with hyaluronic acid (HA) was also successfully fabricated. The nanofibrous structure, water absorption, and compressive mechanical properties of 3D scaffold were studied. Chondrocytes were cultured on 3D scaffold, and their viability and morphology were examined. 3D scaffolds were also subjected to an in vivo cartilage regeneration study on rabbits using an articular cartilage injury model. The results indicated that 3DS-1 and 3DS-2 exhibited superabsorbent property and excellent cytocompatibility. Both these scaffolds present elastic property in the wet state. An in vivo study showed that 3DS-2 could enhance the repair of cartilage. The present 3D nanofibrous scaffold (3DS-2) would be promising for cartilage tissue engineering application.