3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.

Hydrogel scaffolds based on blood plasma cryoprecipitate and collagen derived from various sources: Structural, mechanical and biological characteristics

At present there is a growing need for tissue engineering products,including the products of scaffold-technologies.Biopolymer hydrogel scaffolds have a number of advantages and are increasingly being used to provide means of cell transfer for therapeutic treatments and for inducing tissue regeneration.This work presents original hydrogel biopolymer scaffolds based on a blood plasma cryoprecipitate and collagen and formed under conditions of enzymatic hydrolysis.Two differently originated collagens were used for the scaffold formation.During this work the structural and mechanical characteristics of the scaffold were studied.It was found that,depending on the origin of collagen,scaffolds possess differences in their structural and mechanical characteristics.Both types of hydrogel scaffolds have good biocompatibility and provide conditions that maintain the three-dimensional growth of adipose tissue stem cells.Hence,scaffolds based on such a blood plasma cryoprecipitate and collagen have good prospects as cell carriers and can be widely used in regenerative medicine.

Graphene foam/hydrogel scaffolds for regeneration of peripheral nerve using ADSCs in a diabetic mouse model

The functional recovery of peripheral nerve injury(PNI)is unsatisfactory,whereas diabetes mellitus(DM)and its related complications further attenuate the restoration of diabetic PNI(DPNI).Adipose-derived stem cells(ADSCs)are promising candidates for treatment of DPNI due to their abundant source,excellent differentiation and paracrine ability.Our results showed that ADSCs remarkably enhanced the proliferation and migration of Schwann cells and endothelial cells,and tube formation.Mechanistically,ADSCs could regulate Nrf2/HO-1,NF-κB and PI3K/AKT/mTOR signaling pathways,showing multiple functions in reducing oxidative stress and inflammation,and regulating cell metabolism,growth,survival,proliferation,angiogenesis,differentiation of Schwann cell and myelin formation.In current study,novel graphene foam(GF)/hydrogel-based scaffold was developed to deliver ADSCs for treatment of DPNI.GF/hydrogel scaffold exhibited excellent mechanical strength,suitable porous network,superior electrical conductivity,and good biocompatibility.In vitro results revealed that GF/hydrogel scaffold could obviously accelerate proliferation of Schwann cells.Moreover,in vivo experiments demonstrated that ADSCs-loaded GF/hydrogel scaffold significantly promoted the recovery of DPNI and inhibited the atrophy of targeted muscles,thus providing a novel and attractive therapeutic approach for DPNI patients.

Creating a bionic scaffold via light-curing liquid crystal ink to reveal the role of osteoid-like microenvironment in osteogenesis

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics,including viscoelasticity and liquid crystal(LC)state.Thus,integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair.Despite extensive research on viscoelasticity,the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials.Moreover,the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood.Here,we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink.By utilizing these LC scaffolds as 3D research models,we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation,while viscoelasticity operates via mechanotransduction pathways.Additionally,our investigation revealed a synergistic effect between LC state and viscoelasticity,amplifying cellprotein interactions and osteogenic mechanotransduction processes.Furthermore,the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing.Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis,offering valuable insights for the biomimetic design of bone repair scaffolds.

Multimodal therapy strategies based on hydrogels for the repair of spinal cord injury

Spinal cord injury(SCI)is a serious traumatic disease of the central nervous system,which can give rise to the loss of motor and sensory function.Due to its complex pathological mechanism,the treatment of this disease still faces a huge challenge.Hydrogels with good biocompatibility and biodegradability can well imitate the extracellular matrix in the microenvironment of spinal cord.Hydrogels have been regarded as promising SCI repair material in recent years and continuous studies have confirmed that hydrogel-based therapy can effectively eliminate inflammation and promote spinal cord repair and regeneration to improve SCI.In this review,hydrogel-based multimodal therapeutic strategies to repair SCI are provided,and a combination of hydrogel scaffolds and other therapeutic modalities are discussed,with particular emphasis on the repair mechanism of SCI.

Polyethylene glycol as a promising synthetic material for repair of spinal cord injury

Polyethylene glycol is a synthetic, biodegradable, and water-soluble polyether. Owing to its good biological and material properties, polyethylene glycol shows promise in spinal cord tissue engineering applications. Although studies have examined repairing spinal cord injury with polyethylene glycol, these compelling findings have not been recently reviewed or evaluated as a whole. Thus, we herein review and summarize the findings of studies conducted both within and beyond China that have examined the repair of spinal cord injury using polyethylene glycol. The following summarizes the results of studies using polyethylene glycol alone as well as coupled with polymers or hydrogels：（1） polyethylene glycol as an adjustable biomolecule carrier resists nerve fiber degeneration, reduces the inflammatory response, inhibits vacuole and scar formation, and protects nerve membranes in the acute stage of spinal cord injury.（2） Polyethylene glycol-coupled polymers not only promote angiogenesis but also carry drugs or bioactive molecules to the injury site. Because such polymers cross both the blood-spinal cord and blood-brain barriers, they have been widely used as drug carriers.（3） Polyethylene glycol hydrogels have been used as supporting substrates for the growth of stem cells after injury, inducing cell migration, proliferation, and differentiation. Simultaneously, polyethylene glycol hydrogels isolate or reduce local glial scar invasion, promote and guide axonal regeneration, cross the transplanted area, and re-establish synaptic connections with target tissue, thereby promoting spinal cord repair. On the basis of the reviewed studies, we conclude that polyethylene glycol is a promising synthetic material for use in the repair of spinal cord injury.

Vascularization ability of glioma stem cells in different three-dimensional microenvironments

Glioblastoma(GBM)is among the most common and aggressive adult central nervous system tumors.One prominent charac-teristic of GBM is the presence of abnormal microvessels.A significant correlation between angiogenesis and prognosis has been observed.Accurately reconstructing this neovascula-rization and tumor microenvironment through personalized in vitro disease models presents a significant challenge.However,it is crucial to develop new anti-angiogenic therapies for GBM.In this study,3D bioprinted glioma stem cell(GSC)-laden hydrogel scaffolds,hybrid Gsc hydrogels and ceil-free hydrogel scaffolds were manufactured to investigate the vas-cularization ability of GsCs in varying 3D microenvironments.

Novel crosslinked alginate/hyaluronic acid hydrogels for nerve tissue engineering

CT： Artificial tissue engineering scaffods can potentially provide supportand guidance for the regrowth of severed axons following nerve injury. In this study a hybrid biomaterial composed of alginate and hyaluronic acid （HA） was synthesized characterized in terms of its suitability for covalent modification, biocompatibility fir living Schwann cells and feasibility to construct three dimensional （3D） Carbodiimide mediated amide formation for the purpose of covalent crosslinking of the HA was carried out in the presence of calcium ions that ionically crosslink alginate.Amide formation was found to be dependent on the concentrations of cabodiimide and calclum chloride. The double-crosslinked composite hydrogels display blocompatibllity that is comparable to simple HA hydrogels, allowing for Schwann cell survival and significant difference was found between composite hydrogels made from different of alginate and HA. A 3D BioPIotterTM rapid prototyping system was used to fabricats 3D scaffolds. The result indicated that combining HA with alginate facilitated the fabrication process and that 3D scaffolds with porous inner structure can be fabricated ;from the composite hydrogels, but not from HA alone. This information provides a basis for continuing in vitro and in vivo tests of the suitability of alginate/HA hydrogel as a biomaterial to create living cell scaffolds to support nerve regeneration.

Remote control of the recruitment and capture of endogenous stem cells by ultrasound for in situ repair of bone defects

Stem cell-based tissue engineering has provided a promising platform for repairing of bone defects.However,the use of exogenous bone marrow mesenchymal stem cells(BMSCs)still faces many challenges such as limited sources and potential risks.It is important to develop new approach to effectively recruit endogenous BMSCs and capture them for in situ bone regeneration.Here,we designed an acoustically responsive scaffold(ARS)and embedded it into SDF-1/BMP-2 loaded hydrogel to obtain biomimetic hydrogel scaffold complexes(BSC).The SDF-1/BMP-2 cytokines can be released on demand from the BSC implanted into the defected bone via pulsed ultrasound(p-US)irradiation at optimized acoustic parameters,recruiting the endogenous BMSCs to the bone defected or BSC site.Accompanied by the daily p-US irradiation for 14 days,the alginate hydrogel was degraded,resulting in the exposure of ARS to these recruited host stem cells.Then another set of sinusoidal continuous wave ultrasound(s-US)irradiation was applied to excite the ARS intrinsic resonance,forming highly localized acoustic field around its surface and generating enhanced acoustic trapping force,by which these recruited endogenous stem cells would be captured on the scaffold,greatly promoting them to adhesively grow for in situ bone tissue regeneration.Our study provides a novel and effective strategy for in situ bone defect repairing through acoustically manipulating endogenous BMSCs.

Compatibility of olfactory cnshcathing cells with functionalized self-assembling peptide scaffold in vitro

Background Olfactory ensheathing cell （OEC） transplantation is a promising or potential therapy for spinal cord injury （SCI）. However, the effects of injecting OECs directly into SCI site have been limited and unsatisfied due to the complexity of SCI. To improve the outcome, proper biomaterials are thought to be helpful since these materials would allow the cells to grow three-dimensionally and guide cell miqration.