Hyperspectral digital holography realized by using an electro-optical frequency comb via injection locking.

Hyperspectral digital holography (HSDH) is a versatile holographic imaging technique that offers large unambiguous depth range and spectroscopic information. In this Letter, we propose a novel, to the best of our knowledge, HSDH system that is realized by using an electro-optical frequency comb (EOFC) via injection locking. In comparison with conventional dual-comb HSDH, the proposed system only requires one EOFC and few other devices, which not only simplifies the system structure and reduces the cost but also improves the imaging speed. We validated the system using an EOFC with 20 optical frequencies spaced at 18 GHz intervals. In a total measurement time of 0.5 s, we successfully captured images of two targets that were 0.74 mm apart without phase ambiguity and obtained the transmission spectrum of an absorbing gas simultaneously. This work provides valuable insights for HSDH systems relying on an optical frequency comb.

Optical frequency domain reflectometry with broadened frequency sweep range assisted by a dual electro-optic frequency comb.

We propose an optical frequency domain reflectometry (OFDR) with the assistance of a dual electro-optic frequency comb (EOFC), which is intended to improve the system spatial resolution. As the spatial resolution of an OFDR system is inversely proportional to the frequency sweep range, the EOFC acts as a multi-frequency light source for collecting Rayleigh backscattering signals, which are combined to extend the effective frequency sweep range. By utilizing this technique, we have successfully expanded the experimental frequency sweep range to hundreds of gigahertz, achieving a sub-millimeter spatial resolution.

Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects.

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties, biocompatibility, biodegradability, vasculogenic ability and osteo-inductivity. The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma (PRP)-loaded gelatin methacrylate (GM) and employ them for the regeneration of large-sized bone defects. We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors (GFs) from hydrogels. The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects. For biofunction assay, the GM@PRP hydrogels significantly improved cell migration and angiogenesis. Especially, transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels. The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats. Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis, biomineralization, and collagen deposition. Based on the biocompatibility and biological function of GM@PRP hydrogels, a new strategy is provided for the regenerative repair of large-size bone defects.

Composite superplastic aerogel scaffolds containing dopamine and bioactive glass-based fibers for skin and bone tissue regeneration.

Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization. Microporous GD-BF scaffolds displayed good elastic deformation recovery and promoted neo-tissue formation. The DA could enable thermal crosslinking and enhance the mechanical properties and structural stability of the GD-BF scaffolds. The BGF-mediated release of therapeutic ions shorten hemostatic time (<30 s) in a rat tail amputation model and a rabbit artery injury model alongside inducing the regeneration of skin appendages (e.g., blood vessels, glands, etc.) in a full-thickness excisional defect model in rats (percentage wound closure: GD-BF2, 98 % vs. control group, 83 %) at day 14 in vitro. Taken together, these aerogel scaffolds may have significant promise for soft and hard tissue repair, which may also be worthy for the other related disciplines.

Aspirin-Loaded Anti-Inflammatory ZnO-SiO2 Aerogel Scaffolds for Bone Regeneration.

The increasing aging of the population has elevated bone defects to a significant threat to human life and health. Aerogel, a biomimetic material similar to an extracellular matrix (ECM), is considered an effective material for the treatment of bone defects. However, most aerogel scaffolds suffer from immune rejection and poor anti-inflammatory properties and are not well suited for human bone growth. In this study, we used electrospinning to prepare flexible ZnO-SiO2 nanofibers with different zinc concentrations and further assembled them into three-dimensional composite aerogel scaffolds. The prepared scaffolds exhibited an ordered pore structure, and chitosan (CS) was utilized as a cross-linking agent with aspirin (ASA). Interestingly, the 1%ZnO-SiO2/CS@ASA scaffolds not only exhibited good biocompatibility, bioactivity, anti-inflammation, and better mechanical properties but also significantly promoted vascularization and osteoblast differentiation in vitro. In the mouse cranial defect model, the BV/TV data showed a higher osteogenesis rate in the 1%ZnO-SiO2/CS group (10.94 ± 0.68%) and the 1%ZnO-SiO2/CS@ASA group (22.76 ± 1.83%), compared with the control group (5.59 ± 2.08%), and in vivo studies confirmed the ability of 1%ZnO-SiO2/CS@ASA to promote in situ regeneration of new bone. This may be attributed to the fact that Si4+, Zn2+, and ASA released from 1%ZnO-SiO2/CS@ASA scaffolds can promote angiogenesis and bone formation by stimulating the interaction between endothelial cells (ECs) and BMSCs, as well as inducing macrophage differentiation to the M2 type and downregulating the expression of pro-inflammatory factor (TNF-α) to modulate local inflammatory response. These exciting results and evidence suggest that it provides a new and effective strategy for the treatment of bone defects.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

Shape-Persistent Conductive Nerve Guidance Conduits for Peripheral Nerve Regeneration.

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.

An Injectable Integration of Autologous Bioactive Concentrated Growth Factor and Gelatin Methacrylate Hydrogel with Efficient Growth Factor Release and 3D Spatial Structure for Accelerated Wound Healing.

Growth factors are essential for wound healing owing to their multiple reparative effects. Concentrated growth factor (CGF) is a third-generation platelet extract containing various endogenous growth factors. Herein, a CGF extract solution is combined with gelatin methacrylate (GM) by physical blending to produce GM@CGF hydrogels for wound repair. The GM@CGF hydrogels show no immune rejection during autologous transplantation. Compared to CGF, GM@CGF hydrogels not only exhibit excellent plasticity and adhesivity but also prevent rapid release and degradation of growth factors. The GM@CGF hydrogels display good injectability, self-healing, swelling, and degradability along with outstanding cytocompatibility, angiogenic functions, chemotactic functions, and cell migration-promoting capabilities in vitro. The GM@CGF hydrogel can release various effective molecules to rapidly initiate wound repair, stimulate the expressions of type I collagen, transform growth factor ß1, epidermal growth factor, and vascular endothelial growth factor, promote the production of granulation tissues, vascular regeneration and reconstruction, collagen deposition, and epidermal cell migration, as well as prevent excessive scar formation. In conclusion, the injectable GM@CGF hydrogel can release various growth factors and provide a 3D spatial structure to accelerate wound repair, thereby providing a foundation for the clinical application and translation of CGF.

Injectable nanofiber microspheres modified with metal phenolic networks for effective osteoarthritis treatment.

Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases, which accounts for a large proportion of physical disabilities worldwide. Herein, we fabricated injectable gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospraying technology, which were further modified with tannic acid (TA) named as TMS or metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr2+) and named as TSMS to enhance their bioactivity for OA therapy. The TA-modified microspheres exhibited stable porous structure and anti-oxidative activity. Notably, TSMS showed a sustained release of TA as compared to TMS, which exhibited a burst release of TA. While all types of microspheres exhibited good cytocompatibility, TSMS displayed good anti-inflammatory properties with higher cell viability and cartilage-related extracellular matrix (ECM) secretion. The TSMS microspheres also showed less apoptosis of chondrocytes in the hydrogen peroxide (H2O2)-induced inflammatory environment. The TSMS also inhibited the degradation of cartilage along with the considerable repair outcome in the papain-induced OA rabbit model in vivo as well as suppressed the expression level of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1ß). Taken together, TSMS may provide a highly desirable therapeutic option for intra-articular treatment of OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) is a chronic disease, which is caused by the inflammation of joint. Current treatments for OA achieve pain relief but hardly prevent or slow down the disease progression. Microspheres are at the forefront of drug delivery and tissue engineering applications, which can also be minimal-invasively injected into the joint. Polyphenols and therapeutic ions have been shown to be beneficial for the treatment of diseases related to the joints, including OA. Herein, we prepared gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospinning incorporated electrospraying technology and functionalized them with the metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr2+), and assessed their potential for OA therapy both in vitro and in vivo.

Combined effect of SDF-1 peptide and angiogenic cues in co-axial PLGA/gelatin fibers for cutaneous wound healing in diabetic rats.

Skin regeneration is hindered by poor vascularization, prolonged inflammation, and excessive scar tissue formation, which necessitate newer strategies to simultaneously induce blood vessel regeneration, resolve inflammation, and induce host cell recruitment. Concurrent deployment of multiple biological cues to realize synergistic reparative effects may be an enticing avenue for wound healing. Herein, we simultaneously deployed SDF (stromal cell-derived factor)- 1α, VEGF (vascular endothelial growth factor)-binding peptide (BP), and GLP (glucagon like peptide)- 1 analog, liraglutide (LG) in core/shell poly(L-lactide-co-glycolide)/gelatin fibers to harness their synergistic effects for skin repair in healthy as well as diabetic wound models in rats. Microscopic techniques, such as SEM and TEM revealed fibrous and core/shell type morphology of membranes. Boyden chamber assay and scratch-wound assay displayed significant migration of HUVECs (human umbilical vein endothelial cells) in SDF-1α containing fibers. Subcutaneous implantation of membranes revealed higher cellular infiltration in SDF-1α loaded fibers, especially, those which were co-loaded with LG or BP. Implantation of membranes in an excisional wound model in healthy rats further showed significant and rapid wound closure in dual cues loaded groups as compared to control or single cue loaded groups. Similarly, the implantation of dressings in type 2 diabetes rat model revealed fast healing, skin appendages regeneration, and blood vessel regeneration in dual cues loaded fibers (SDF-1α/LG, SDF-1α/BP). Taken together, core/shell type fibers containing bioactive peptides significantly promoted wound repair in healthy as well as diabetic wound models in rats.

Current Advancements and Strategies of Biomaterials for Tendon Repair: A Review.

Tendon is a bundle of tissue comprising of a large number of collagen fibers that connects muscle to bone. However, overuse or trauma may cause degeneration and rupture of the tendon tissues, which imposes an enormous health burden on patients. In addition to autogenous and allogeneic transplantation, which is commonly used in the clinic, the current research on tendon repair is focused on developing an appropriate scaffold via biomaterials and fabrication technology. The development of a scaffold that matches the structure and mechanics of the natural tendon is the key to the success of the repair, so the synergistic optimization of the scaffold fabrication technology and biomaterials has always been a concern of researchers. A series of strategies include the preparation of scaffolds by electrospinning and 3D printing, as well as the application of injectable hydrogels and microspheres, which can be used individually or in combination with cells, growth factors for tendon repair. This review introduces the tendon tissue structure, the repair process, the application of scaffolds, and the current challenges facing biomaterials, and gives an outlook on future research directions. With biomaterials and technology continuing to be developed, we envision that the scaffolds could have an important impact on the application of tendon repair.

On the development of modular polyurethane-based bioelastomers for rapid hemostasis and wound healing.

Massive hemorrhage may be detrimental to the patients, which necessitates the advent of new materials with high hemostatic efficiency and good biocompatibility. The objective of this research was to screen for the effect of the different types of bio-elastomers as hemostatic dressings. 3D loose nanofiber sponges were prepared; PU-TA/Gel showed promising potential. Polyurethane (PU) was synthesized and electrospun to afford porous sponges, which were crosslinked with glutaraldehyde (GA). FTIR and 1H-NMR evidenced the successful synthesis of PU. The prepared PU-TA/Gel sponge had the highest porosity and water absorption ratio. Besides, PU-TA/Gel sponges exhibited cytocompatibility, negligible hemolysis and the shortest clotting time. PU-TA/Gel sponge rapidly induced stable blood clots with shorter hemostasis time and less bleeding volume in a liver injury model in rats. Intriguingly, PU-TA/Gel sponges also induced good skin regeneration in a full-thickness excisional defect model as revealed by the histological analysis. These results showed that the PU-TA/Gel-based sponges may offer an alternative platform for hemostasis and wound healing.

Evaluation of natural protein-based nanofiber composite photocrosslinking hydrogel for skin wound regeneration.

Protein based photocrosslinking hydrogels with nanofiber dispersions were reported to be an effective wound dressing. In this study, two kinds of protein (gelatin and decellularized dermal matrix) were modified to obtain GelMA and ddECMMA, respectively. Poly(ε-caprolactone) nanofiber dispersions (PCLPBA) and thioglycolic acid-modified chitosan (TCS) were added into GelMA solution and ddECMMA solution, respectively. After photocrosslinking, four kinds of hydrogel (GelMA, GTP4, DP and DTP4) were fabricated. The hydrogels showed excellent physico-chemical property, biocompatibility and negligible cytotoxicity. When applied on the full-thickness cutaneous deficiency of SD rats, hydrogel treated groups exhibited an enhanced wound healing effect than Blank group. Besides, the histological staining of H&E and Masson's showed that hydrogels groups with PCLPBA and TCS (GTP4 and DTP4) improved wound healing. Furthermore, GTP4 group performed better healing effect than other groups, which had great potential in skin wound regeneration.

Chondroitin sulfate cross-linked three-dimensional tailored electrospun scaffolds for cartilage regeneration.

Degenerated cartilage tissues remain a burgeoning issue to be tackled, while bioactive engineering products available for optimal cartilage regeneration are scarce. In the present study, two-dimensional (2DS) poly(l-lactide-co-ε-caprolactone)/silk fibroin (PLCL/SF)-based scaffolds were fabricated by conjugate electrospinning method, which were then cross-linked with chondroitin sulfate (CS) to further enhance their mechanical and biological performance. Afterwards, three-dimensional (3D) PLCL/SF scaffolds (3DS) and CS-crosslinked 3D scaffolds (3DCSS) with tailored size were successfully fabricated by an in-situ gas foaming in a confined mold followed by freeze-dried. Gas-foamed scaffolds displayed high porosity, rapid water uptake, and stable mechanical properties. While all of the scaffolds exhibited good cytocompatibility in vitro; 3DCSS showed better cell seeding efficiency and chondro-protective effect compared to other scaffolds. Besides, 3DCSS scaffolds supported the formation of more mature cartilage-like tissues along with the best repair outcome in a rabbit articular cartilage defect model in vivo, as well as less expression level of pro-inflammatory cytokines, including interleukin (IL)-1ß and tumor necrosis factor (TNF)-α than that of the other groups. Taken together, 3DCSS may provide an alternative therapeutic option for cartilage tissue repair.

Synergistic effect of glucagon-like peptide-1 analogue liraglutide and ZnO on the antibacterial, hemostatic, and wound healing properties of nanofibrous dressings.

Bacterial infections and poor vascularization delay wound healing, thus necessitating alternative strategies for functional wound dressings. Zinc oxide (ZnO) has been shown to exert a potent antibacterial effect against bacterial species. Similarly, Glucagon-like peptide-1 (GLP-1) analogue liraglutide (LG) has been shown to promote vascularization and improve wound healing. The objective of this research was to investigate the synergistic effect of ZnO nanoparticles (ZnO-NPs) and LG to simultaneously induce antibacterial, hemostatic, and vascularization effects for infected wound healing. Electrospun poly (l-lactide-co-glycolide)/gelatin (PLGA/Gel) membranes containing ZnO-NPs and LG displayed good biocompatibility and hemostatic ability. Both, ZnO-NPs and LG exhibited synergistic antibacterial effect against Staphylococcus aureus and Escherichia coli as well as improved the migration and tubule-like network formation of human umbilical vein endothelial cells (HUVECs) in vitro. Once evaluated in a bacterial-infected wound model in rats, the membranes loaded with ZnO-NPs and LG effectively promoted wound healing causing significant reduction in wound area and scar-like tissue formation. Therefore, ZnO-NPs/LG synergism may offer an invaluable solution for the treatment of poorly healing infected wounds.

Vascular Endothelial Growth Factor-Capturing Aligned Electrospun Polycaprolactone/Gelatin Nanofibers Promote Patellar Ligament Regeneration.

Ligament injuries are common in sports and other rigorous activities. It is a great challenge to achieve ligament regeneration after an injury due the avascular structure and low self-renewal capability. Herein, we developed vascular endothelial growth factor (VEGF)-binding aligned electrospun poly(caprolactone)/gelatin (PCL/Gel) scaffolds by incorporating prominin-1-binding peptide (BP) sequence and exploited them for patellar ligament regeneration. The adsorption of BP onto scaffolds was discerned by various techniques, such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and confocal laser scanning microscope. The accumulation of VEGF onto scaffolds correlated with the concentration of the peptide in vitro. BP-anchored PCL/Gel scaffolds (BP@PCL/Gel) promoted the tubular formation of human umbilical vein endothelial cells (HUVECs) and wound healing in vitro. Besides, BP containing scaffolds exhibited higher content of CD31+ cells than that of the control scaffolds at 1 week after implantation in vivo. Moreover, BP containing scaffolds improved biomechanical properties and facilitated the regeneration of matured collagen in patellar ligament 4 weeks after implantation in mice. Overall, this strategy of peptide-mediated orchestration of VEGF provides an enticing platform for the ligament regeneration, which may also have broad implications for tissue repair applications. STATEMENT OF SIGNIFICANCE: Ligament injuries are central to sports and other rigorous activities. Given to the avascular nature and poor self-healing capability of injured ligament tissues, it is a burgeoning challenge to fabricate tissue-engineered scaffolds for ligament reconstruction. Vascular endothelial growth factor (VEGF) is pivotal to the neo-vessel formation. However, the high molecular weight of VEGF as well as its short half-life in vitro and in vivo limits its therapeutic potential. To circumvent these limitations, herein, we functionalized aligned electrospun polycaprolactone/gelatin (PCL/Gel)-based scaffolds with VEGF-binding peptide (BP) and assessed their biocompatibility and performance in vitro and in vivo. BP-modified scaffolds accumulated VEGF, improved tube formation of HUVECs, and induced wound healing in vitro, which may have broad implications for regenerative medicine and tissue engineering.

Converging 3D Printing and Electrospinning: Effect of Poly(l-lactide)/Gelatin Based Short Nanofibers Aerogels on Tracheal Regeneration.

Recently, various tissue engineering based strategies have been pursued for the regeneration of tracheal tissues. However, previously developed tracheal scaffolds do not accurately mimic the microstructure and mechanical behavior of the native trachea, which restrict their clinical translation. Here, tracheal scaffolds are fabricated by using 3D printing and short nanofibers (SF) dispersion of poly(l-lactide)/gelatin (0.5-1.5 wt%) to afford tracheal constructs. The results display that the scaffolds containing 1.0 wt % of SF exhibit low density, good water absorption capacity, reasonable degradation rate, and stable mechanical properties, which were comparable to the native trachea. Moreover, the designed scaffolds possess good biocompatibility and promote the growth and infiltration of chondrocytes in vitro. The biocompatibility of tracheal scaffolds is further assessed after subcutaneous implantation in mice for up to 4 and 8 weeks. Histological assessment of tracheal constructs explanted at week 4 shows that scaffolds can maintain their structural integrity and support the formation of neo-vessels. Furthermore, cell-scaffold constructs gradually form cartilage-like tissues, which mature with time. Collectively, these engineered tracheal scaffolds not only possess appropriate mechanical properties to afford a stabilized structure but also a biomimetic extracellular matrix-like structure to accomplish tissue regeneration, which may have broad implications for tracheal regeneration.

Conjugate Electrospun 3D Gelatin Nanofiber Sponge for Rapid Hemostasis.

Developing an excellent hemostatic material with good biocompatibility and high blood absorption capacity for rapid hemostasis of deep non-compressible hemorrhage remains a significant challenge. Herein, a novel conjugate electrospinning strategy to prepare an ultralight 3D gelatin sponge consisting of continuous interconnected nanofibers. This unique fluffy nanofiber structure endows the sponge with low density, high surface area, compressibility, and ultrastrong liquid absorption capacity. In vitro assessments show the gelatin nanofiber sponge has good cytocompatibility, high cell permeability, and low hemolysis ratio. The rat subcutaneous implantation studies demonstrate good biocompatibility and biodegradability of gelatin nanofiber sponge. Gelatin nanofiber sponge aggregates and activates platelets in large quantities to accelerate the formation of platelet embolism, and simultaneously escalates other extrinsic and intrinsic coagulation pathways, which collectively contribute to its superior hemostatic capacity. In vivo studies on an ear artery injury model and a liver trauma model of rabbits demonstrate that the gelatin nanofiber sponge rapidly induce stable blood clots with least blood loss compared to gelatin nanofiber membrane, medical gauze, and commercial gelatin hemostatic sponge. Hence, the gelatin nanofiber sponge holds great potential as an absorbable hemostatic agent for rapid hemostasis.

Three-dimensional porous gas-foamed electrospun nanofiber scaffold for cartilage regeneration.

To achieve optimal functional recovery of articular cartilage, scaffolds with nanofibrous structure and biological function have been widely pursued. In this study, two-dimensional electrospun poly(l-lactide-co-ε-caprolactone)/silk fibroin (PLCL/SF) scaffolds (2DS) were fabricated by dynamic liquid support (DLS) electrospinning system, and then cross-linked with hyaluronic acid (HA) to further mimic the microarchitecture of native cartilage. Subsequently, three-dimensional PLCL/SF scaffolds (3DS) and HA-crosslinked three-dimensional scaffolds (3DHAS) were successfully fabricated by in situ gas foaming and freeze-drying. 3DHAS exhibited better mechanical properties than that of the 3DS. Moreover, all scaffolds exhibited excellent biocompatibility in vitro. 3DHAS showed better proliferation and phenotypic maintenance of chondrocytes as compared to the other scaffolds. Histological analysis of cell-scaffold constructs explanted 8 weeks after implantation demonstrated that both 3DS and 3DHAS scaffolds formed cartilage-like tissues, and the cartilage lacuna formed in 3DHAS scaffolds was more mature. Moreover, the reparative capacity of scaffolds was discerned after implantation in the full-thickness articular cartilage model in rabbits for up to 12 weeks. The macroscopic and histological results exhibited typical cartilage-like character and well-integrated boundary between 3DHAS scaffolds and the host tissues. Collectively, biomimetic 3DHAS scaffolds may be promising candidates for cartilage tissue regeneration applications.