Composite Hydrogel System Research Articles

Thermal and NIR controlled flexible switching devices using a smart conductive composite hydrogel approach

Flexible switching devices with multi-stimulus responsive abilities have shown promising applications as smart materials in the tissue regeneration fields. Herein, a composite hydrogel-based flexible switch system was successfully designed by integrating the nano-sized conductive CNC@PPy (cellulose nanocrystal decorated with polypyrrole (PPy)) and CNC@PDA (cellulose nanocrystal decorated with polydopamine (PDA)) composite particles into the thermal sensitive poly N-isopropyl acrylamide (PNIPAM) hydrogels. The resulting composite hydrogels exhibited enhanced elastic modulus (∼29.5 kPa), superior conductivity (∼1.1 S/m), self-healing, and thermo- and NIR-responsive abilities. Particularly, the incorporated CNC@PDA and CNC@PPy particles within the hydrogel matrix by hydrogen bonds could not only provide a more continuous transporting path for electrons, but also further improve the photothermal conversion efficiency of the composite hydrogel system, in which the temperature increased by 47.6 °C within 10 min under NIR irradiation, and high NIR light-responsive sensitivity with a volume change of 30% within 2 min. Moreover, these composite hydrogels were developed to serve thermo- and NIR light-responsive switchers effectively, which showed excellent stimulus-responsive sensitivities. In all, this work provided a new strategy for designing the multi-stimulus responsive smart hydrogels, which demonstrated excellent potential to serve as remotely controllable switch devices in biomaterials and tissue regeneration.

MSC‐Laden Composite Hydrogels for Inflammation and Angiogenic Regulation for Skin Flap Repair

AbstractPressure‐driven, spreadable, deferoxamine (DFO)‐laden hydrogels are developed toward treatment for improved skin flap tissue repair. Further, mesenchymal stem cells (MSCs) are incorporated into silk nanofiber systems and then added to silk hydrogels to optimize angiogenesis and moderate inflammatory reactions in skin flap tissues for repair. The combined (composite) systems result in improved tissue outcomes. For example, the DFO release from the hydrogels is maintained while the system moderated negative influences of DFO on cells at the skin flap site with improved vasculization and for control of immune reactions. Both in vitro and in vivo results reveal improved outcomes with these composite hydrogel systems when MSCs are included. The synergistic action of DFO‐laden silk nanofibers combined with MSC‐laden microgels results in improved functional recovery of skin flaps in vivo when compared to control systems. Considering the ease of use of this system toward clinical applications, these new hydrogels are candidates for skin flap regeneration in surgical settings.

Elucidating the combinatorial effect of substrate stiffness and surface viscoelasticity on cellular phenotype.

Cells maintain tensional homeostasis by monitoring the mechanics of their microenvironment. In order to understand this mechanotransduction phenomenon, hydrogel materials have been developed with either controllable linear elastic or viscoelastic properties. Native biological tissues, and biomaterials used for medical purposes, often have complex mechanical properties. However, due to the difficulty in completely decoupling the elastic and viscous components of hydrogel materials, the effect of complex composite materials on cellular responses has largely gone unreported. Here, we characterize a novel composite hydrogel system capable of decoupling and individually controlling both the bulk stiffness and surface viscoelasticity of the material by combining polyacrylamide (PA) gels with microgel thin films. By taking advantage of the high degree of control over stiffness offered by PA gels and viscoelasticity, in terms of surface loss tangent, of microgel thin films, it is possible to study the influence that bulk substrate stiffness and surface loss tangent have on complex fibroblast responses, including cellular and nuclear morphology and gene expression. This material system provides a facile method for investigating cellular responses to complex material mechanics with great precision and allows for a greater understanding of cellular mechanotransduction mechanisms than previously possible through current model material platforms.

Spatiotemporal regulation of endogenous MSCs using a functional injectable hydrogel system for cartilage regeneration

Hydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.

Donut-like MOFs of copper/nicotinic acid and composite hydrogels with superior bioactivity for rh-bFGF delivering and skin wound healing

BackgroundSkin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis.ResultsHerein, we have prepared a new donut-like metal–organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers.ConclusionsConsidering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.Graphic abstract

3D-Printable Hierarchical Nanogel-GelMA Composite Hydrogel System.

The strength of the extracellular matrix (ECM) is that it is hierarchical in terms of matrix built-up, matrix density and fiber structure, which allows for hormones, cytokines, and other small biomolecules to be stored within its network. The ECM-like hydrogels that are currently used do not possess this ability, and long-term storage, along with the need for free diffusion of small molecules, are generally incompatible requirements. Nanogels are able to fulfill the additional requirements upon successful integration. Herein, a stable hierarchical nanogel–gelatin methacryloyl (GelMA) composite hydrogel system is provided by covalently embedding nanogels inside the micropore network of GelMA hydrogel to allow a controlled local functionality that is not found in a homogenous GelMA hydrogel. Nanogels have emerged as a powerful tool in nanomedicine and are highly versatile, due to their simplicity of chemical control and biological compatibility. In this study, an N-isopropylacrylamide-based nanogel with primary amine groups on the surface was modified with methacryloyl groups to obtain a photo-cross-linking ability similar to GelMA. The nanogel-GelMA composite hydrogel was formed by mixing the GelMA and the photo-initiator within the nanogel solution through UV irradiation. The morphology of the composite hydrogel was observed by scanning electron microscopy, which clearly showed the nanogel wrapped within the GelMA network and covering the surface of the pore wall. A release experiment was conducted to prove covalent bonding and the stability of the nanogel inside the GelMA hydrogel. In addition, 3D printability studies showed that the nanogel-GelMA composite ink is printable. Therefore, the suggested stable hierarchical nanogel-GelMA composite hydrogel system has great potential to achieve the in situ delivery and controllable release of bioactive molecules in 3D cell culture systems.

Biofabrication of Cell-Laden Gelatin Methacryloyl Hydrogels with Incorporation of Silanized Hydroxyapatite by Visible Light Projection.

Gelatin methacryloyl (GelMA) hydrogel is a photopolymerizable biomaterial widely used for three-dimensional (3D) cell culture due to its high biocompatibility. However, the drawback of GelMA hydrogel is its poor mechanical properties, which may compromise the feasibility of biofabrication techniques. In this study, a cell-laden GelMA composite hydrogel with a combination incorporating silanized hydroxyapatite (Si-HAp) and a simple and harmless visible light crosslinking system for this hydrogel were developed. The incorporation of Si-HAp into the GelMA hydrogel enhanced the mechanical properties of the composite hydrogel. Moreover, the composite hydrogel exhibited low cytotoxicity and promoted the osteogenic gene expression of embedded MG63 cells and Human bone marrow mesenchymal stem cells (hBMSCs). We also established a maskless lithographic method to fabricate a defined 3D structure under visible light by using a digital light processing projector, and the incorporation of Si-HAp increased the resolution of photolithographic hydrogels. The GelMA-Si-HAp composite hydrogel system can serve as an effective biomaterial in bone regeneration.

Growth factor-loaded microspheres in mPEG-polypeptide hydrogel system for articular cartilage repair.

We developed an injectable hydrogel system with a sustained release of TGF-β3 through growth factor-loaded microsphere to mimic the cartilage-like microenvironment. Poly(lactic-co-glycolic acid) (PLGA) microspheres incorporated in three dimensional (3D) scaffolds were chosen because of its regulatory approval, good biodegradability, and acting as carriers with sustained release behavior. We evaluated sustained release of TGF-β3 by PLGA microspheres encapsulated in methoxy poly(ethylene glycol)-poly(alanine) (mPA) hydrogels and the resulting enhanced chondrogenic effects. We reported here the effect of the proposed system for sustained release of growth factors on chondrogenesis in cartilage regeneration. PLGA microspheres were used in our thermosensitive mPA hydrogel system with bovine serum albumin as a stabilizing and protecting agent for the emulsion and TGF-β3 enabling sustained release. Gelation, structural properties, and in-vitro release of this composite, that is, microspheres in hydrogel, system were investigated. Using PLGA microspheres to carry growth factors could complement the mPA hydrogel's ability to provide an excellent 3D microenvironment for the promotion of chondrogenic phenotype as compared the systems using mPA hydrogel or microspheres alone. Our study demonstrated that this synthesized composite hydrogel system is capable of modulating the biosynthetic and differentiation activities of chondrocytes. The sustained release of TGF-β3 in this novel hydrogel system could improve biomedical applicability of mPEG-polypeptide scaffolds. The distinctive local growth factor delivery system successfully combined the use of both polymers to be a suitable candidate for prolonged articular cartilage regeneration.

In Vitro 3D Models of Tunable Stiffness.

Three-dimensional models of spheroid formation have been routinely used in the cancer field to test the colony forming capacity of malignant cells in an in vitro setting. Use of such a model provides a robust surrogate for in vivo testing, enabling large-scale interrogation into the effect of certain treatment conditions. This adapted protocol describes a high throughput and readily accessible composite alginate hydrogel system for spheroid formation, within a biomechanically tunable three-dimensional environment. This model therefore allows users to examine the effect of certain treatment conditions while cells are embedded within a hydrogel of defined stiffness. This is particularly important in the context of cancer where cells experience a wide range of mechanical properties within their microenvironment, driven by widespread changes in the extracellular matrix composition and architecture.This protocol describes a high-throughput method which results in homogeneous interpenetrating polymer networks of collagen and alginate. We show that this network readily supports single-cell spheroid formation in numerous malignant cell lines (breast cancer, lung cancer, and melanoma) and that these can be robustly analyzed for colony formation measures such as spheroid size, spheroid number, and overall cell viability; therefore, allowing users to undertake high-throughput, in vitro screening against a controlled biomechanical background.

A pH/redox-dual responsive, nanoemulsion-embedded hydrogel for efficient oral delivery and controlled intestinal release of magnesium ions.

It remains a major challenge to achieve efficient oral delivery and controlled intestinal release of ions using hydrogels. Herein, we report a novel, pH/redox-dual responsive, nanoemulsion-embedded composite hydrogel to address this issue. The hydrogel was first synthesized by crosslinking a biocompatible, pH-responsive pseudopeptide, poly(l-lysine isophthalamide) (PLP), and redox-sensitive l-cystine dimethyl ester dihydrochloride (CDE). A suitable amount of magnesium acetate was encapsulated into oil-in-water nanoemulsions, which were then embedded into the lysine-based hydrogel. The resulting composite hydrogel collapsed into a compact structure at acidic gastric pH, but became highly swollen or degraded in the neutral and reducing intestinal environment. The ion release profiles indicated that the nanoemulsion-embedded composite hydrogel could well retain and protect magnesium ions in the simulated gastric fluid (SGF) buffer at pH 1.2, but efficiently release them in the simulated intestinal fluid (SIF) buffer at pH 6.8 in the presence of 1,4-dithiothreitol (DTT) as a reducing agent. Moreover, this composite hydrogel system displayed good biocompatibility. These results suggested that the pH/redox-dual responsive, nanoemulsion-embedded composite hydrogel could be a promising candidate for efficient oral delivery and controlled intestinal release of magnesium and other ions.

Synthesis of uniformly dispersed silica/graphene oxide composite hydrogel using acid/base combinatorial catalysts system

This study involved the preparation of a sol–gel-based silica hydrogel, which incorporates uniformly dispersed graphene oxide (GO), using an acid/base combinatorial catalyst system. The gelation time of the silica hydrogel was dramatically reduced by adding the combinatorial catalyst instead of using a single catalyst system. Raman mapping confirmed that the combinatorial catalyst system considerably improved the uniformity of GO dispersion in the silica matrix. The silica/GO composite hydrogel demonstrated a very wide range of elastic moduli, compressive strength, and strain at fracture, indicating that this composite hydrogel system could potentially be used as a platform for stem cell culture or as a stretchable gel.

Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy

Surgery is the final choice for most patients with intervertebral disc degeneration (IDD). Operation-caused trauma will cause inflammation in the intervertebral disc. Serious inflammation will cause tissue defects and induce tissue degeneration, IDD recurrence and the occurrence of other diseases. Therefore, we proposed a scheme to treat recurrence after discectomy by inhibiting inflammation with an aspirin (ASP)-loaded hydrogel to restore the mechanical stability of the spine and relieve local inflammation. ASP-liposomes (ASP-Lips) were incorporated into a photocrosslinkable gelatin-methacryloyl (GelMA) via mixing. This material can effectively alleviate inflammation by inhibiting the release of high mobility group box 1 (HMGB1) from the nucleus to the cytoplasm. We further assessed the expression of inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and degeneration-related factors, such as type II collagen (COL-2), Aggrecan, matrix metallopeptidases-3 (MMP-3), MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 in rat nucleus pulpous cells. The level of IDD was analyzed through H&E, safranin-O staining and immunohistochemistry in rabbit samples. In vitro, we found that ASP-Lip@GelMA treatment significantly decreased inflammatory cytokines, MMP-3 and -13, and ADAMTS-4 and -5 and up-regulated COL-2 and Aggrecan via the inhibited release of HMGB-1 from the nucleus. In vivo, ASP-Lip@GelMA can effectively inhibit inflammation of local tissue after disc surgery and fill local tissue defects. This composite hydrogel system is a promising way to treat the recurrence of IDD after surgery without persistent complications.

Bioprinting of patient-derived in vitro intrahepatic cholangiocarcinoma tumor model: establishment, evaluation and anti-cancer drug testing

Towards the development of in vivo-mimicking tumor model for extensive study of tumorigenesis and establishment of personalized therapy, patient-derived primary tumor cells were employed in this work for three-dimensional (3D) bioprinting. Intrahepatic cholangiocarcinoma cells isolated from patient were bioprinted using a composite hydrogel system of gelatin-alginate-MatrigelTM into pre-designed grid architecture. ICC cells were observed to process a colony forming ability with high survival rate and active proliferation. Expression levels of tumor markers, cancer stem cell markers, matrix metalloproteinase protein, index of tumor fibrosis, index of liver function, and epithelial-mesenchymal transition regulatory proteins confirmed the development of the invasive and metastatic phenotype of the intrahepatic cholangiocarcinoma cells in the 3D printed tumor microenvironment. Similar results were obtained in anti-cancer drug resistance of the intrahepatic cholangiocarcinoma cells in the 3D bioprinted construct that demonstrated stem-like properties, which suggested the promising potential of current 3D printed tumor model in the development of personalized therapy, especially for discovery of more conducive targeted drugs.

Composite Hydrogels in Three-Dimensional in vitro Models.

3-dimensional (3D) in vitro models were developed in order to mimic the complexity of real organ/tissue in a dish. They offer new possibilities to model biological processes in more physiologically relevant ways which can be applied to a myriad of applications including drug development, toxicity screening and regenerative medicine. Hydrogels are the most relevant tissue-like matrices to support the development of 3D in vitro models since they are in many ways akin to the native extracellular matrix (ECM). For the purpose of further improving matrix relevance or to impart specific functionalities, composite hydrogels have attracted increasing attention. These could incorporate drugs to control cell fates, additional ECM elements to improve mechanical properties, biomolecules to improve biological activities or any combinations of the above. In this Review, recent developments in using composite hydrogels laden with cells as biomimetic tissue- or organ-like constructs, and as matrices for multi-cell type organoid cultures are highlighted. The latest composite hydrogel systems that contain nanomaterials, biological factors, and combinations of biopolymers (e.g., proteins and polysaccharide), such as Interpenetrating Networks (IPNs) and Soft Network Composites (SNCs) are also presented. While promising, challenges remain. These will be discussed in light of future perspectives toward encompassing diverse composite hydrogel platforms for an improved organ environment in vitro.

Novel Hydrogels and Composite Hydrogels Based on ԑ-Polylysine, Hyaluronic Acid and Hydroxyapatite

At this work hydrogel and composite hydrogel systems based on ԑ-polylysine (EPL), hyaluronic acid (HA) and nanocrystalline hydroxyapatite (nHAp) were synthesized via chemical cross-linking method followed by in situ precipitation of nHAp into hydrogel copolymer matrix. Molecular structure, phase composition and morphology of EPL-HA and EPL-HA/nHAp systems were investigated using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffractometry (XRD) and scanning electron microscopy (SEM). The fabricated hydrogels and composite hydrogels were evaluated by hydrogels characteristics such as gel fraction and swelling behavior. This study provides a new insight to develop cutting-edge bioactive hydrogels and composite hydrogels for bone tissue engineering as injectable biomaterials due to beneficial properties of system components.

Synthesis of photocrosslinkable hydrogels for engineering three-dimensional vascular-like constructs by surface tension-driven assembly.

Surface tension-driven assembly is a simple routine used in modular tissue engineering to create three-dimensional (3D) biomimetic tissues with desired structural and biological characteristics. A major bottleneck for this technology is the lack of suitable hydrogel materials to meet the requirements of the assembly process and tissue regeneration. Identifying specific requirements and synthesizing novel hydrogels will provide a versatile platform for generating additional biomimetic functional tissues using this approach. In this paper, we present a novel composite hydrogel system based on methacrylated gelatin and γ-polyglutamic acid by UV copolymerization as the building block for fabricating vascular-like tissue via surface tension-driven assembly. The resulting composite hydrogels exhibited the improved mechanical properties and hydrophilicity, which greatly facilitate the assembly process. Subsequent cell encapsulation experiment proved that the hydrogel could provide 3D support for cellular spreading and migration. Furthermore, based on the composite microgel building blocks, cylindrical vascular-like construct with a perfusable microchannel was generated by the needle-assisted sequential assembly. In order to construct a biomimetic vascular tissue, the endothelial cells and smooth muscle cells were encapsulated in the microgels assembly with a spatial arrangement to build a heterogeneous double-layer tubular structure and the cells could readily elongate and migrate in the hollow concentric construct over 3days. These data suggest that this composite hydrogel is an attractive candidate for surface tension-driven assembly purposes, making the hydrogel potentially applicable in the fabrication of biomimetic vascularized tissues.

Sustained Release of Melatonin from GelMA Liposomes Reduced Osteoblast Apoptosis and Improved Implant Osseointegration in Osteoporosis.

A reduction in bone mass around an implant is the main cause of implant loosening, especially in postmenopausal osteoporosis patients. In osteoporosis, excessive oxidative stress, resulting in osteoblast apoptosis, largely contributes to abnormal bone remodeling. Melatonin (MT) synthesized by the pineal gland promotes osteoblast differentiation and bone formation and has been effectively used to combat oxidative stress. Therefore, we hypothesized that MT attenuates osteoblast apoptosis induced by oxidative stress, promotes osteogenesis in osteoporosis, and improves bone mass around prostheses. Moreover, considering the distribution and metabolism of MT, its systemic administration would require a large amount of MT, increasing the probability of drug side effects, so the local administration of MT is more effective than its systemic administration. In this study, we constructed a composite adhesive hydrogel system (GelMA-DOPA@MT) to bring about sustained MT release in a local area. Additionally, MT-reduced apoptosis caused by hydrogen peroxide- (H2O2-) induced oxidative stress and restored the osteogenic potential of MC3T3-E1 cells. Furthermore, apoptosis in osteoblasts around the implant was significantly attenuated, and increased bone mass around the implant was observed in ovariectomized (OVX) rats treated with this composite system. In conclusion, our results show that GelMA-DOPA@MT can inhibit osteoblast apoptosis caused by oxidative stress, thereby promoting osteogenesis and improving bone quality around a prosthesis. Therefore, this system of local, sustained MT release is a suitable candidate to address implant loosening in patients with osteoporosis.

3D Printing of Stem Cell Responsive Ionically-Crosslinked Polyethylene Glycol Diacrylate/ Alginate Composite Hydrogels Loaded with Basic Fibroblast Growth Factor for Dental Pulp Tissue Engineering: A Preclinical Evaluation in Animal Model

The main aim of this study was to develop a 3D printed stem cell-responsive polyethylene glycol diacrylate (PEGDA) and sodium alginate (SA) composite hydrogel system (PEGDA/SA) loaded with basic fibroblast growth factor (bFGF) suitable for dental pulp tissue engineering. The PEGDA/SA loaded with bFGF (PEGDA/SA-bFGF) at different concentration ratios were 3D printed via stereolithography (SLA) under optimal processing conditions, followed by ionic crosslinking. The morphological and porous structure of the 3D printed PEGDA/SA-bFGF constructs and release profile of the bFGF were analyzed. The cellular compatibility of the hydrogel constructs was evaluated using human dental pulp stem cells (hDPSCs)in vitro. Subsequently, biocompatibility and tissue regenerative potential of the hydrogel constructs were evaluated in immunodeficient mice model. The in vitro cell culture results of PEGDA/SA-bFGF constructs exhibited high cell compatibility and supported cell proliferation, irrespective of their concentration ratios. Thein vivo animal experiment results showed that the hDPSCs-laden PEGDA/SA (PEGDA/SA-hDPSCs) group failed to form a good pulp structure even at various concentration ratios. When the mass ratio of PEGDA/SA was 25:1, hDPSCs-laden PEGDA/SA-bFGF (PEGDA/SA-bFGF-hDPSCs) group also failed to form dental pulp-like tissue but a partial loose connective tissue formation was observed. However, when the mass ratio of PEGDA/SA reduces to 20:1 ~ 15:1, the PEGDA/SA-bFGF-hDPSCs group tends to form a well-organized pulp structure post 4 weeks implantation, thus highlighting the potential of this particular hydrogel scaffolding system for dental pulp tissue regenerative applications.

Cellulose-based injectable hydrogel composite for pH-responsive and controllable drug delivery

Cellulose-based biocompatible, tunable and injectable hydrogels embedded with pH-responsive diblock copolymer micelles were constructed to achieve localized drug delivery with prolonged, stimuli-driven and slow-release function. First, we prepared two types of modified carboxymethyl cellulose (CMC) including hydrazide-modified carboxymethyl cellulose (CMC-NH2) and oxidized carboxymethyl cellulose (CMC−CHO) with varying degrees of oxidation. Then, pH-responsive poly (ethylene oxide)-block-poly (2-(diisopropylamino) ethyl methacrylate) (PEO-b-PDPA) copolymers as micelle cores to carry hydrophobic substances were also synthesized through atom transfer radical polymerization (ATRP). An injectable hydrogel composite system was finally obtained by mixing CMC-NH2 and CMC−CHO polymer suspensions containing PEO-b-PDPA copolymer micelles through a Schiff base reaction. This newly-synthesized, tunable, cellulose-based double barrier system exhibits a pH-triggered, prolonged, and slow-release profile based on the release test using both Nile Red dye and doxorubicin. The hydrogel system also exhibited comparable storage moduli and tunable degradation properties.

In Situ Osteochondral Regeneration by Controlled Release of Stromal Cell-Derived Factor-1 Chemokine from Injectable Biomaterials: A Preclinical Evaluation in Animal Model

Osteochondral defect (OD) refers to damage in the area of articular cartilage extended to the subchondral bone, affecting millions of people worldwide. In situ osteochondral tissue engineering approach, which aims to activate the body's native stem cells and recruit them to the defective site by utilizing biomaterials, has become a potential strategy for repairing focal chondral lesions. However, due to the lack of cell-instructive potential, most of the biomaterials fail to recruit stem cells from the host environment and trigger the cellular and molecular functions necessary for tissue regeneration. In this study, the authors report a new formulation of injectable biomaterial system, based on stromal cell-derived factor-1 (SDF-1)-encapsulated poly(lactic-co-glycolic acid) (PLGA) microspheres loaded chitosan-gelatin (CS-GEL) composite hydrogel system (SDF-1/CS-GEL@PLGA), with the aim of imparting in situ cell-instructive and osteochondral tissue regenerative potential. The osteochondral regenerative potential of SDF-1/CS-GEL@PLGA was studied in rabbit as a model animal and the results were compared with the CS-GEL@PLGA without the SDF-1. The results of this study showed that the CS-GEL@PLGA hydrogel had better gelation time and longer release cycle (>30 days) than the CS-GEL. In addition, SDF-1/CS-GEL@PLGA hydrogels promoted the repair of osteochondral defects in rabbits within 12 weeks as compared to the CS-GEL@PLGA hydrogels. Therefore, based on the experimental data, SDF-1/CS-GEL@PLGA hydrogel is a promising injectable biomaterial system for osteochondral repair and regeneration.