Injectable Scaffold Research Articles

Cellulose nanocrystals-reinforced dual crosslinked double network GelMA/hyaluronic acid injectable nanocomposite cryogels with improved mechanical properties for cartilage tissue regeneration.

Improvement of mechanical properties of injectable tissue engineering scaffolds is a current challenge. The objective of the current study is to produce a highly porous injectable scaffold with improved mechanical properties. For this aim, cellulose nanocrystals-reinforced dual crosslinked porous nanocomposite cryogels were prepared using chemically crosslinked methacrylated gelatin (GelMA) and ionically crosslinked hyaluronic acid (HA) through the cryogelation process. The resulting nanocomposites showed highly porous structures with interconnected porosity (>90%) and mean pore size in the range of 130-296 μm. The prepared nanocomposite containing 3%w/v of GelMA, 20 w/w% of HA, and 1%w/v of CNC showed the highest Young's modulus (10 kPa) and excellent reversibility after 90% compression and could regain its initial shape after injection by a 16-gauge needle in the aqueous media. The in vitro results demonstrated acceptable viability (>90%) and migration of the human chondrocyte cell line (C28/I2), and chondrogenic differentiation of human adipose stem cells. A two-month in vivo assay on a rabbit's ear model confirmed that the regeneration potential of the prepared cryogel is comparable to the natural autologous cartilage graft, suggesting it is a promising alternative for autografts in the treatment of cartilage defects.

Injectable Mesocellular Foam Silica Microparticles with a Dual Role of Cell‐Recruiting Scaffolds and Intracellular Delivery Vehicles for Enhanced Cancer Vaccine

AbstractThe cancer vaccine is one of the potent cancer immunotherapies based on provoking antigen‐specific adaptive immune responses in patients. Activating host antigen‐presenting cells by delivering antigens and adjuvants is one of the most important requirements to enhance cancer vaccine efficacy. This study proposes an effective cancer vaccine platform based on injectable mesocellular foam (MCF) silica microparticles with a dual role capable of in situ recruitment of host dendritic cells (DCs) and intracellular delivery of antigens to the recruited DCs. Subcutaneously administrated MCF microparticles loaded with chemoattractant to DCs (GM‐CSF), antigenic protein (OVA), and TLR9 agonist (CpG‐ODN) lead to robust DC maturation and high antigen‐specific T cell responses. The cell recruitment, DC activation, and T cell responses of MCF‐based cancer vaccine are significantly higher than injectable mesoporous silica scaffold, of which role is mostly limited to the cell recruiting scaffold. These features of MCF lead to effective inhibition of tumor growth in prophylactic vaccine setting and lung metastatic cancer model, representing MCF enabling cell‐recruiting scaffold formation and intracellular delivery of antigen can be a promising material platform for an enhanced cancer vaccine.

Thermoresponsive Injectable Hydrogel To Mimic the Heat- and Strain-Stiffening Behavior of Biopolymers toward Muscle Cell Proliferation.

Injectable hydrogels with nonlinear mechanical attributes to emulate natural biopolymers hold paramount significance in tissue engineering, offering the potential to create scaffolds that seamlessly mimic the biomechanical intricacies of living tissues. Herein, we unveil a synthetic design strategy employing Schiff base chemistry to furnish a peptide-polymer hierarchical contractile injectable hydrogel network. This innovative design demonstrates cross-linking of supramolecular peptide nanostructures such as nanofibers, 1NF, and twisted bundles, 1TB, with a thermosensitive aldehyde-functionalized polymer, PCHO. These networks exhibit interesting nonlinear mechanical stiffening responses to temperature and external stress. Furthermore, the hydrogels transform into a gel state at physiological temperature to exhibit injectable behavior and demonstrate compression load-bearing capabilities. Finally, the hydrogel network exhibits excellent biocompatibility and cell proliferation toward fibroblast, L929, and myoblast, C2C12, to validate their use as potential extracellular matrix mimetic injectable scaffolds.

Injectable and Photocurable Gene Scaffold Facilitates Efficient Repair of Spinal Cord Injury.

RNA interference-based gene therapy has led to a strategy for spinal cord injury (SCI) therapy. However, there have been high requirements regarding the optimal gene delivery vector for siRNA-based SCI gene therapy. Here, we developed an injectable and photocurable lipid nanoparticle GelMA (PLNG) hydrogel scaffold for controlled dual siRNA delivery at the SCI wound site. The prepared PLNG scaffold could efficiently protect and retain the bioactivity of the siRNA nanocomplex. It facilitated sustainable siRNA release along with degradation in 7 days. After loading dual siRNA targeting phosphatase and tensin homologue (PTEN) and macrophage migration inhibitory factor (MIF) simultaneously, the locally administered siRNAs/PLNG scaffold efficiently improved the Basso mouse scale (BMS) score and recovered ankle joint movement and plantar stepping after treatment with only three doses. We further proved that the siRNAs/PLNG scaffold successfully regulated the activities of neurons, microglia, and macrophages, thus promoting neuron axon regeneration and remyelination. The protein array results suggested that the siRNAs/PLNG scaffold could increase the expression of growth factors and decrease the expression of inflammatory factors to regulate neuroinflammation in SCI and create a neural repair environment. Our results suggested that the PLNG scaffold siRNA delivery system is a potential candidate for siRNA-based SCI therapy.

Fabrication of an injectable hydrogel scaffold embedding kartogenin-encapsulated PLGA microsphere with long-term drug release to promote chondrogenesis

To address the long-lasting challenges on repair of articular cartilage defects in clinic, cartilage tissue engineering (CTE) strategy aims to develop favorable scaffolds to undertake mechanical support and simulate the cellular microenvironment for remodeling or replacing the defective cartilage tissues. Wherein, facile operation, favorable mechanical strength, excellent biocompatibility, suitable biodegradability, and innate chondrogenic ability are crucially adjective in CTE. Herein, we fabricated an injectable tetra-PEG hydrogel scaffold embedding kartogenin-encapsulated poly (lactic-co-glycolic acid) (PLGA@KGN) microspheres by means of the premix membrane emulsification (PME) method and quick sol-gel transformation. The unform tetra-PEG network endowed this composite hydrogel (tetra-PEG/PLGA@KGN) with favorable pores, easy injectability, mechanical strength and lower swelling ratio, while the internal small KGN drugs with the unique differentiation ability into chondrocytes could be slowly released for a long period of time, thus capably allowing the maintenance of the drug's effective concentration and long-lasting sustained release up to >28 days and persistently enhancing its chondrogenic efficiency. In vitro results indicated its satisfactory compatibility for supporting the cell activity, proliferation, and differentiation. Overall, due to improved mechanical property and sustainable KGN release behavior, this designable hydrogel scaffold may provide an option with clinical translational potential for cartilage repair.

A sodium alginate/carboxymethyl chitosan dual-crosslinked injectable hydrogel scaffold with tunable softness/hardness for bone regeneration

Recently, injectable dual-crosslinked (DC) hydrogel scaffolds have attracted many attentions as a class of excellent bone regeneration biomaterials with in-situ tunable functions. However, the design of injectable DC hydrogels with cell behavior-compatible network structure and mechanical property remains a bottleneck. Herein, based on the in-situ gelling method, we constructed an injectable CMCS/PEG+SA/CaCl2 (CPSC) chemical/physical DC hydrogel scaffold with tunable softness/hardness mechanical properties and good biocompatibility. The formation mechanism and properties of the CPSC hydrogel scaffold were investigated by FTIR, XRD, rheometry, and mechanical testing. It is found that proper softness/hardness mechanical properties can be obtained by adjusting the secondary network structure of the hydrogel. The CPSC hydrogel scaffold prepared under optimal conditions can effectively promote cell infiltration, nutrient transport, and the osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs). The in vivo experiments show that the rBMSCs-loaded injectable CPSC hydrogels with appropriate mechanical properties can effectively promote bone reconstruction. This study has provided important guidance for the construction of injectable DC hydrogels with adjustable softness/hardness to promote osteogenesis for bone defect repair.

Biomaterial-Based Sustained-Release Drug Formulations for Localized Cancer Immunotherapy.

Cancer immunotherapy has revolutionized clinical cancer treatments by taking advantage of the immune system to selectively and effectively target and kill cancer cells. However, clinical cancer immunotherapy treatments often have limited efficacy and/or present severe adverse effects associated primarily with their systemic administration. Localized immunotherapy has emerged to overcome these limitations by directly targeting accessible tumors via local administration, reducing potential systemic drug distribution that hampers drug efficacy and safety. Sustained-release formulations can prolong drug activity at target sites, which maximizes the benefits of localized immunotherapy to increase the therapeutic window using smaller dosages than those used for systemic injection, avoiding complications of frequent dosing. The performance of sustained-release formulations for localized cancer immunotherapy has been validated preclinically using various implantable and injectable scaffold platforms. This review introduces the sustained-release formulations developed for localized cancer immunotherapy and highlights their biomaterial-based platforms for representative classes, including inorganic scaffolds, natural hydrogels, synthetic hydrogels, and microneedle patches. The design rationale and other considerations are summarized for further development of biomaterials for the construction of optimal sustained-release formulations.

Biomimetic injectable and bilayered hydrogel scaffold based on collagen and chondroitin sulfate for the repair of osteochondral defects

The simultaneous regeneration of articular cartilage and subchondral bone is a major challenge. Bioinspired scaffolds with distinct regions resembling stratified anatomical architecture provide a potential strategy for osteochondral defect repair. Here, we report the development of an injectable and bilayered hydrogel scaffold with a strong interface binding force. In this bilayer hydrogel, composed of carbonyl hydrazide grafted collagen (COL-CDH) and oxidized chondroitin sulfate (OCS), which are derivatives of osteochondral tissue components, in combination with poly (ethylene glycol) diacrylate (PEGDA), functions as a cartilage layer; while zinc-doped hydroxyapatite acts as a subchondral bone layer that is based on the cartilage layer. The strong interface between the two layers involves dynamic amide bonds formed between COL-CDH and OCS, and permanent CC bonds formed by PEGDA radical reactions. This bilayer hydrogel can be used to inoculate adipose mesenchymal stem cells which can then differentiate into chondrocytes and osteoblasts, secreting glycosaminoglycan, and promoting calcium deposition. This accelerates the regeneration of cartilage and subchondral bone. Micro-CT and tissue staining revealed an increase in the amount of bone present in new subchondral bone, and new tissues with a structure similar to normal cartilage. This study therefore demonstrates that injectable bilayer hydrogels are a promising scaffold for repairing osteochondral defects.

E2-Loaded Microcapsules and Bone Marrow-Derived Mesenchymal Stem Cells with Injectable Scaffolds for Endometrial Regeneration Application.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been recognized as new candidates for the treatment of serious endometrial injuries. However, owing to the local microenvironment of damaged endometrium, transplantation of BMSCs yielded disappointing results. In this study, Pectin-Pluronic® F-127 hydrogel as scaffolds were fabricated to provide three-dimensional architecture for the attachment, growth, and migration of BMSCs. E2 was encapsulated into the W/O/W microspheres to construct pectin-based E2-loaded microcapsules (E2 MPs), which has the potential to serve as a long-term reliable source of E2 for endometrial regeneration. Then, the BMSCs/E2 MPs/scaffolds system was injected into the uterine cavity of mouse endometrial injury model for treatment. At 4 weeks after transplantation, the system increased proliferative abilities of uterine endometrial cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive an embryo, suggesting that the BMSCs/E2 MPs/scaffolds system is a promising treatment option for endometrial regeneration. Furthermore, the mechanism of E2 in promoting the repair of endometrial injury was also investigated. Exosomes are critical paracrine mediators that act as biochemical cues to direct stem cell differentiation. In this study, it was found that the expression of endometrial epithelial cell (EEC) markers was upregulated in BMSCs treated by exosomes secreted from endometrial stromal cells (ESCs-Exos). Exosomes derived from E2-stimulated ESCs further promoted the expression level of EECs markers in BMSCs, suggesting exosomes released from ESCs by E2 stimulation could enhance the differentiation efficiency of BMSCs. Therefore, exosomes derived from ESCs play paracrine roles in endometrial regeneration stimulated by E2 and provide optimal estrogenic response.

Injectable Microporous Annealed Crescent-Shaped (MAC) Particle Hydrogel Scaffold for Enhanced Cell Infiltration.

Hydrogels are widely used for tissue engineering applications to support cellular growth, yet the tightly woven structure often restricts cell infiltration and expansion. Consequently, granular hydrogels with microporous architectures have emerged as a new class of biomaterial. Particularly, the development of microporous annealed particle (MAP) hydrogel scaffolds has shown improved stability and integration with host tissue. However, the predominant use of spherically shaped particles limits scaffold porosity, potentially limiting the level of cell infiltration. Here, a novel microporous annealed crescent-shaped particle (MAC) scaffold that is predicted to have improved porosity and pore interconnectivity in silico is presented. With microfluidic fabrication, tunable cavity sizes that optimize interstitial void space features are achieved. In vitro, cells incorporated into MAC scaffolds form extensive 3D multicellular networks. In vivo, the injectable MAC scaffold significantly enhances cell infiltration compared to spherical MAP scaffolds, resulting in increased numbers of myofibroblasts and leukocytes present within the gel without relying on external biomolecular chemoattractants. The results shed light on the critical role of particle shape in cell recruitment, laying the foundation for MAC scaffolds as a next-generation granular hydrogel for diverse tissue engineering applications.

Injectable phase-separated tetra-armed poly(ethylene glycol) hydrogel scaffold allows sustained release of growth factors to enhance the repair of critical bone defects

With the rising prevalence of bone-related injuries, it is crucial to improve treatments for fractures and defects. Tissue engineering offers a promising solution in the form of injectable hydrogel scaffolds that can sustain the release of growth factors like bone morphogenetic protein-2 (BMP-2) for bone repair. Recently, we discovered that tetra-PEG hydrogels (Tetra gels) undergo gel-gel phase separation (GGPS) at low polymer content, resulting in hydrophobicity and tissue affinity. In this work, we examined the potential of a newer class of gel, the oligo-tetra-PEG gel (Oligo gel), as a growth factor-releasing scaffold. We investigated the extent of GGPS occurring in the two gels and assessed their ability to sustain BMP-2 release and osteogenic potential in a mouse calvarial defect model. The Oligo gel underwent a greater degree of GGPS than the Tetra gel, exhibiting higher turbidity, hydrophobicity, and pore formation. The Oligo gel demonstrated sustained protein or growth factor release over a 21-day period from protein release kinetics and osteogenic cell differentiation studies. Finally, BMP-2-loaded Oligo gels achieved complete regeneration of critical-sized calvarial defects within 28 days, significantly outperforming Tetra gels. The easy formulation, injectability, and capacity for sustained release makes the Oligo gel a promising candidate therapeutic biomaterial.

Bone-Adhesive Hydrogel for Effective Inhibition of M. tuberculosis and Osteoblast Regeneration.

Currently, bone tuberculosis (TB) treatment largely involves lifelong drug prescriptions and surgical intervention, resulting in poor quality of life for patients. Therefore, the fabrication of injectable scaffolds to form a solid framework around the defective bone region is gaining importance over the extensive use of antimicrobial inhibitors. Herein, we synthesized a novel bone-adhesive and thermoresponsive hydrogel via conjugation of poly(N-isopropylacrylamide-co-glycidyl methacrylate) (PNIPAM-co-GMA) and cysteine (CYS). Thiolation of the polymer enables chemical cross-linking with the bone glycoprotein, enhancing bone adhesion and permitting control of scaffold retention time. The PNIPAM-co-GMA-CYS hydrogel shows higher cross-linking behavior at 37 °C, forms a strong gel in 260 s, and has 151 kPa adhesion strength on cortical bone. The lead compounds 5-methyl-5H-[1,2,4]triazino[5,6-b]indole-3-thiol (MTIT) and N-tert-butyl-4-methyl-6-(5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-ylthio)pyrimidin-2-amine (TMTIPA) were identified by a high-throughput screening method. Effective MTIT and TMTIPA are encapsulated in bone-adhesive hydrogel separately, and both have a high release rate above >70% in 180 h. The MTIT- and TMTIPA-loaded PNIPAM-co-GMA-CYS showed an excellent bactericidal effect, reducing the relative intracellular bacterial survival in macrophages. Furthermore, the as-synthesized hydrogel has outstanding mechanical and biocompatibility properties to become a bone-replacing material and provide support to promote bone repair. This work presents a novel bone-adhesive PNIPAM-co-GMA-CYS for the sustained release of lead compounds toward promising alternative bone TB treatment.

Spinal fusion of biodegradable poly(propylene fumarate) and poly(propylene fumarate-co-caprolactone) copolymers in rabbits

BackgroundAutologous bone grafts are currently the standard in orthopedic surgery despite limited donor sources and the prevalence of donor site morbidity. Other alternatives such as allografts are more readily available than autografts but have lower rates of graft incorporation. MethodsHere, we propose a novel graft alternative consisting of an injectable poly(propylene fumarate) (PPF) and poly(propylene fumarate-co-caprolactone) P(PF-co-CL) copolymer with a recombinant human bone morphogenetic protein-2 (rhBMP-2)/vascular epithelial growth factor (VEGF) release system accompanied by hydroxyapatite (HA). The efficacy of scaffold formulations was studied using a standard, bilateral, L-level (L5-L6) posterolateral transverse spinal fusion using New Zealand white rabbits. Rabbits were divided into 4 experimental groups: group I, negative control; group II, autograft (positive control); group III, injectable PPF scaffold with rhBMP-2/VEGF release system and HA; group IV, injectable P(PF-co-CL)scaffold with rhBMP-2/VEGF release system and HA. Spines were harvested at 6 weeks and 12 weeks after surgery, and spinal fusions were assessed using manual palpation, radiographic analysis, micro-computed tomography (μCT) assessment, and histologic analysis. ResultsOf the 4 experimental groups, the injectable P(PF-co-CL) scaffold displayed superior initial strength and faster degradation than scaffolds constructed from PPF alone and facilitated the fusion of lateral processes in the rabbit standard posterolateral spinal fusion model. The results obtained from manual palpation, radiology, and μCT showed no difference between the P(PF-co-CL) group and the PPF group. However, histologic sections showed more osteogenesis with the new injectable P(PF-co-CL) scaffold. ConclusionInjectable P(PF-co-CL) polymers showed promising spine fusion abilities in rabbits after 12 weeks of posterolateral implantation.

An injectable carboxymethyl chitosan hydrogel scaffold formed via coordination bond for antibacterial and osteogenesis in osteomyelitis

The intricate, hostile, and diverse nature of osteomyelitis (OM) poses a challenge for complete bacterial eradication and osteogenesis promotion via conventional treatment. Recently, functional hydrogels exhibiting antibacterial and osteogenic properties emerge as a promising avenue for OM wound healing in clinical practice. However, the preparation procedures and associated costs on cytokine and cell therapies for certain functional hydrogels can be complex and prohibitively expensive. In our research, a hybrid hydrogel dressing has been formulated utilizing carboxymethyl chitosan (CMCS) as the base material, and designed with inherent antibacterial, adhesion, proliferation, and differentiation characteristics, showing promise as a candidate for eradicating infection and promoting bone regeneration. The hybrid hydrogel is composed of interconnected networks of Fe3+-induced self-assembled CMCS and the antibacterial drug ciprofloxacin (CIP), resulting in excellent injectability and moldability. Notably, the CMCS/Fe3+/CIP hybrid hydrogel is capable of regulating antibacterial responses and stimulating osteogenesis in infected microenvironments without additional additives. This injectable antibacterial and osteogenic-promoting hydrogel establish a high-potential platform for low-cost, safe and effective treatment of OM by expediting the initial stages of infected bone wound repair.

Injectable periodontal ligament stem cell-metformin-calcium phosphate scaffold for bone regeneration and vascularization in rats.

Injectable and self-setting calcium phosphate cement scaffold (CPC) capable of encapsulating and delivering stem cells and bioactive agents would be highly beneficial for dental and craniofacial repairs. The objectives of this study were to: (1) develop a novel injectable CPC scaffold encapsulating human periodontal ligament stem cells (hPDLSCs) and metformin (Met) for bone engineering; (2) test bone regeneration efficacy in vitro and in vivo. hPDLSCs were encapsulated in degradable alginate fibers, which were then mixed into CPC paste. Five groups were tested: (1) CPC control; (2) CPC +hPDLSC-fibers +0% Met (CPC + hPDLSCs + 0%Met); (3) CPC +hPDLSC-fibers +0.1% Met (CPC + hPDLSCs + 0.1%Met); (4) CPC +hPDLSC-fibers +0.2% Met (CPC + hPDLSCs + 0.2%Met); (5) CPC +hPDLSC-fibers +0.4% Met (CPC + hPDLSCs + 0.4%Met). The injectability, mechanical properties, metformin release, and hPDLSC osteogenic differentiation and bone mineral were determined in vitro. A rat cranial defect model was used to evaluate new bone formation. The novel construct had good injectability and physical properties. Alginate fibers degraded in 7 days and released hPDLSCs, with 5-fold increase of proliferation (p＜0.05). The ALP activity and mineral synthesis of hPDLSCs were increased by Met delivery (p＜0.05). Among all groups, CPC+hPDLSCs+0.1%Met showed the greatest cell mineralization and osteogenesis, which were 1.5-10folds those without Met (p＜0.05). Compared to CPC control, CPC+hPDLSCs+0.1%Met enhanced bone regeneration in rats by 9 folds, and increased vascularization by 3 folds (p＜0.05). The novel injectable construct with hPDLSC and Met encapsulation demonstrated excellent efficacy for bone regeneration and vascularization in vivo in an animal model. CPC+hPDLSCs+0.1%Met is highly promising for dental and craniofacial applications.

Methyl Cellulose based in situ Hydrogel for Controlled Drug Delivery and Tissue Engineering Application

Methyl cellulose is an attractive smart biomaterial for its thermoreversible gelation nature. When subjected to temperature stimuli, an aqueous solution containing methyl cellulose at a critical concentration exhibits the ability to form stable physically cross-linked hydrogels. These hydrogels alter the physico-chemical and mechanical properties of the methyl cellulose. This thermo-responsive nature become quite appealing when the physiological temperature functions as a trigger to regulate the thermogelation of methyl cellulose. Regarding this, exciting inventions have been explored in the drug delivery and tissue engineering field which make methyl cellulose an attractive and versatile biomaterial. In this review, we have covered traditional and advanced applications of methyl cellulose as thermoreversible in situ gelling system. Three main types of applications are presented: (i) in situ gelling system for controlled drug delivery; (ii) fabrication of injectable scaffolds and cell sheet for tissue engineering application; and finally (iii) developing methyl cellulose based bioink for 3D bioprinting by applying in situ thermogelation property of methyl cellulose.

Injectable and Self-Adaptive Gel Scaffold Based on Heparin Microspheres for Adipogenesis of Human Adipose-Derived Stem Cells.

An injectable and self-adaptive heparin microsphere-based cell scaffold was developed to achieve adipose regeneration. Simultaneously, the cell scaffold exhibited a dynamic architecture, self-regulated glucose levels, sustained insulin delivery, and steady viscoelastic properties for adipogenesis. The dynamic cell scaffold is cross-linked by the boronate-diol interaction among heparin-based microspheres, which have boronate and maltose groups. Because of the boronate-maltose ester bonds, the gelatinous complex would be partially dismantled and readily display glucose-sensitive performance by free glucose via competitive displacement. The dynamic cross-linking heparin microsphere scaffold can deliver the lipogenic drug insulin to enhance lipid filling, which has an impact on fat tissue enhancement. A 4-week in vitro cell culture demonstrated that the dynamic heparin microsphere-based cell scaffold, through loading with insulin, showed significantly higher efficiency in promoting ASC differentiation compared with traditional 3D culture methods. In vivo histological results further demonstrated that there was a significant increase in adipose in the proposed cell scaffold, which proved to be statistically significant compared with traditional biomaterials. Notable stain expression of the FABP4 and PPAR-γ genes was also observed in the dynamic cell scaffold containing insulin, which was more similar to natural fat.

Injectable Thermosensitive Hyaluronic Acid Hydrogels for Chondrocyte Delivery in Cartilage Tissue Engineering.

In this study, we synthesize a hyaluronic acid-g-poly(N-isopropylacrylamide) (HPN) copolymer by grafting the amine-terminated poly(N-isopropylacrylamide) (PNIPAM-NH2) to hyaluronic acid (HA). The 5% PNIPAM-NH2 and HPN polymer solution is responsive to temperature changes with sol-to-gel phase transition temperatures around 32 °C. Compared with the PNIPAM-NH2 hydrogel, the HPN hydrogel shows higher water content and mechanical strength, as well as lower volume contraction, making it a better choice as a scaffold for chondrocyte delivery. From an in vitro cell culture, we see that cells can proliferate in an HPN hydrogel with full retention of cell viability and show the phenotypic morphology of chondrocytes. In the HPN hydrogel, chondrocytes demonstrate a differentiated phenotype with the upregulated expression of cartilage-specific genes and the enhanced secretion of extracellular matrix components, when compared with the monolayer culture on tissue culture polystyrene. In vivo studies confirm the ectopic cartilage formation when HPN was used as a cell delivery vehicle after implanting chondrocyte/HPN in nude mice subcutaneously, which is shown from a histological and gene expression analysis. Taken together, the HPN thermosensitive hydrogel will be a promising injectable scaffold with which to deliver chondrocytes in cartilage-tissue-engineering applications.

Injectable pH and Thermo-Responsive Hydrogel Scaffold with Enhanced Osteogenic Differentiation of Preosteoblasts for Bone Regeneration.

Bone fractures are common in the geriatric population and pose a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remain several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration, given their high performance in filling irregularly sized bone defects and their ability to encapsulate cells and bioactive molecules and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote the differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts, as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.

Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells promotes functional recovery in patients with spontaneous intracerebral hemorrhage: phase I clinical trial.

Animal experiments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury. To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage, this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion criteria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People's Armed Police Force from May 2016 to December 2020. Patients were divided into three groups according to the clinical situation and patient benefit: control (n = 18), human umbilical cord-derived mesenchymal stem cells (n = 4), and combination (n = 8). The control group did not receive any transplantation. The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation. The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells. Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intracerebral hemorrhage-related encephalomalacia. Severe adverse events associated with cell transplantation were not observed. Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.