Soft Tissue Engineering Research Articles

Surface charge dominated protein absorption on hydrogels

Soft tissue engineering requires antifouling materials that are biocompatible and mechanically flexible. Conventional hydrogels containing more than 70 wt% water are thus promising antifouling material candidates. However, some hydrogels are difficult to apply in internal body organs because of undesirable protein absorption on their surfaces. Due to the lack of an effective method for observing the true charge densities of hydrogels, the reason why electrostatic interactions dominate protein absorption behavior remains unclear. In this work, we adopt the microelectrode technique (MET) to study the electrical potentials of hydrogels with negative, positive, and neutral potentials and demonstrate the protein absorption behaviors on those hydrogels. The results show that MET is an effective method to obtain the surface charge densities of various hydrogels. Furthermore, the amounts of absorbed proteins on the gels were quantified with respect to the charge densities of the hydrogels. The results indicate that electrostatic absorption is quantitatively dominated by a combination of hydrogel charge density and overall protein charge. Based on the knowledge obtained in this work, the effects of hydrogel surface charges on protein absorption can be better understood. Thus, the results are expected to promote the application of hydrogels in tissue engineering.

Biofunctionalization of zirconia with cell-adhesion peptides via polydopamine crosslinking for soft tissue engineering: effects on the biological behaviors of human gingival fibroblasts and oral bacteria.

Rapid soft tissue integration is essential for long-term dental implant success. Zirconia is increasingly used as an abutment material owing to its excellent aesthetic properties and biocompatibility; however, it is bioinert, and tissue integration is poor. We developed a feasible surface modification method, exploiting the reactivity of polydopamine (PDA) films to immobilize cell-adhesion peptides (Arg-Gly-Asp, RGD) onto zirconia abutment surfaces. Further, we evaluated the effect thereof on human gingival fibroblast (HGF) behavior and oral bacterial adhesion, which influence the peri-implant soft tissue seal. HGF responses to linear KGGRGDSP and cyclic RGDfK sequences were compared. PDA deposition and covalent coupling of RGD were verified by X-ray photoelectron spectroscopy and fluorescence microscopy. The biological behaviors of HGFs on the modified zirconia; i.e., adhesion, spreading, proliferation, gene and protein expression, were elucidated. Biofunctionalization of zirconia with the adhesion peptides significantly enhanced the biological activities of HGFs. Cyclic RGD induced slightly improved cell attachment, spreading, and proliferation, but similar cell differentiation when compared to linear RGD peptides. To assess their antimicrobial properties, the different substrates were exposed to cultures of the early colonizer Streptococcus mutans or the periodontal pathogen Porphyromonas gingivalis, and bacterial adhesion was evaluated by scanning electron microscopy and live/dead staining. PDA and PDA-RGD coatings decreased zirconia surface colonization by both bacterial species to similar extents. Thus, PDA-RGD-functionalized zirconia modulates specific HGF responses, while maintaining the antimicrobial activity of the PDA coating. The selective bio-interaction pattern of this surface modification holds great promise for improving soft-tissue integration around zirconia abutments in clinical applications.

High Throughput Manufacturing of Bio-Resorbable Micro-Porous Scaffolds Made of Poly(L-lactide-co-ε-caprolactone) by Micro-Extrusion for Soft Tissue Engineering Applications.

Porous scaffolds made of elastomeric materials are of great interest for soft tissue engineering. Poly(L-lactide-co-ε-caprolactone) (PLCL) is a bio-resorbable elastomeric copolymer with tailorable properties, which make this material an appropriate candidate to be used as scaffold for vascular, tendon, and nerve healing applications. Here, extrusion was applied to produce porous scaffolds of PLCL, using NaCl particles as a leachable agent. The effects of the particle proportion and size on leaching performance, dimensional stability, mechanical properties, and ageing of the scaffolds were analyzed. The efficiency of the particle leaching and scaffold swelling when wet were observed to be dependent on the porogenerator proportion, while the secant moduli and ultimate tensile strengths were dependent on the pore size. Porosity, swelling, and mechanical properties of the extruded scaffolds were tailorable, varying with the proportion and size of porogenerator particles and showed similar values to human soft tissues like nerves and veins (E = 7–15 MPa, σu = 7 MPa). Up to 300-mm length micro-porous PLCL tube with 400-µm thickness wall was extruded, proving extrusion as a high-throughput manufacturing process to produce tubular elastomeric bio-resorbable porous scaffolds of unrestricted length with tunable mechanical properties.

Cell-Encapsulating Hydrogel Puzzle: Polyrotaxane-Based Self-Healing Hydrogels.

Slide-ring hydrogels using polyrotaxanes have been developed as highly tough soft materials. However, they have never been used as biomaterials because of the lack of biocompatibility. Meanwhile, self-healing hydrogels are expected to improve fatigue resistance and extend the period of use. However, owing to the lack of high mechanical strength, they are limited in their use as biomaterials. Here we first developed a biocompatible self-healing/slide-ring hydrogel using glycol chitosan and a water-soluble polyrotaxane. We obtained excellent mechanical toughness and biocompatibility to promote the proliferation of human umbilical vein endothelial cells (HUVECs) encapsulated in the hydrogel. Owing to the rapid self-healing property, the cell-encapsulating gels adjusted arbitrarily, maintaining good cell proliferation function. Therefore, slide-ring hydrogels enable the use of biomaterials for soft-tissue engineering.

Poly(Glycerol Sebacate)-Poly(l-Lactide) Nonwovens. Towards Attractive Electrospun Material for Tissue Engineering.

Two types of poly(glycerol sebacate) (PGS) prepolymers were synthesized and electrospun with poly(l-lactic acid) (PLA), resulting in bicomponent nonwovens. The obtained materials were pre-heated in a vacuum, at different times, to crosslink PGS and investigate morphological and structural dependencies in that polymeric, electrospun system. As both PGS and PLA are sensitive to pre-heating (crosslinking) conditions, research concerns both components. More interest is focused on the properties of PGS, considering further research for mechanical properties and subsequent experiments with PGS synthesis. Electrospinning of PGS blended with PLA does not bring difficulties, but obtaining elastomeric properties of nonwovens is problematic. Even though PGS has many potential advantages over other polyesters when soft tissue engineering is considered, its full utilization via the electrospinning process is much harder in practice. Further investigations are ongoing, especially with the promising PGS prepolymer with a higher esterification degree and its variations.

3D bioprinted alginate-gelatin based scaffolds for soft tissue engineering

Increase in the number of patients suffering from Osteoarthritis is prevalent nowadays and hence, there is need for tissue regeneration. Fabricating a 3D structure giving a better control mimicking the actual tissue properties, especially for osteo-chondral applications is a challenge due to several constraints (like suitable biomaterial for cell encapsulation, mimicking mechanical properties). Here, we mimic the natural process of tissue formation by encapsulating cells in an optimized 3D construct which improves mechanical properties by matrix secretion. We investigated different concentrations of Alginate-Gelatin ink and further characterized the optimized concentration. Behaviour of different infill percentage on the bioactivity and morphology of the scaffold was also investigated. For observing the behaviour of cells on different infill percentages within the scaffolds of same concentration, we used osteoblasts (MG63) cells. The optimized material concentration with the adequate infill showed printability, adequate viscosity, and increased swelling. Both, 20 and 25% infill within the Alginate-Gelatin scaffolds (2.5% w/v Alginate and 5% w/v Gelatin) resulted in higher viability and proliferation of osteoblast cells. Additionally, to control the shape retention ability of the scaffolds dual crosslinking was applied. Thus, the developed Alginate-Gelatin based 3D scaffold maintains the required balance between biomechanics and soft tissue regeneration.

Tough and biocompatible hybrid networks prepared from methacrylated poly(trimethylene carbonate) (PTMC) and methacrylated gelatin

Hybrid networks of PTMC and gelatin were prepared and their mechanical and biological properties were investigated. First, PTMC oligomer and gelatin were methacrylated. Methacrylated macromers, PTMC-dMA and GelMA, were dissolved in DMSO/formic acid (90/10 v/v) at concentrations of 30% or 23% (w/v), at room temperature (RT) or 65 °C. Subsequently, mixtures were prepared at 75:25, 50:50 and 25:75 ratios (v/v) of PTMC-dMA and GelMA. Hybrid networks and networks of only PTMC or gelatin were prepared by solvent casting followed by photo-crosslinking. Mechanical properties were investigated by tensile testing and biological properties by human smooth muscle cell proliferation on the surface of the networks. Although incorporation of gelatin in PTMC networks decreased the toughness of the networks, networks consisting of 75% PTMC and 25% gelatin still had adequate mechanical properties, e.g. for vascular tissue engineering. Hybrid networks prepared at 30% (w/v) macromer concentration at RT had the highest toughness. Cell proliferation on all hybrid networks was similar to that on 100% gelatin networks and significantly higher than on 100% PTMC networks. It is concluded that incorporation of 25% gelatin in a PTMC network is a viable strategy to increase cellular interactions with the network, while retaining sufficient mechanical properties for soft tissue engineering applications.

High-Resolution 3D Printing of Stretchable Hydrogel Structures Using Optical Projection Lithography.

Double-network (DN) hydrogels, with their unique combination of mechanical strength and toughness, have emerged as promising materials for soft robotics and tissue engineering. In the past decade, significant effort has been devoted to synthesizing DN hydrogels with high stretchability and toughness; however, shaping the DN hydrogels into complex and often necessary user-defined two-dimensional (2D) and three-dimensional (3D) geometries remains a fabrication challenge. Here, we report a new fabrication method based on optical projection lithography to print DN hydrogels into customizable 2D and 3D structures within minutes. DN hydrogels were printed by first photo-crosslinking a single network structure via spatially modulated light patterns followed by immersing the printed structure in a calcium bath to induce ionic cross-linking. Results show that DN structures made by this method can stretch four times their original lengths. We show that strain and the elastic modulus of printed structures can be tuned based on the hydrogel composition, cross-linker and photoinitiator concentrations, and laser light intensity. To our knowledge, this is the first report demonstrating quick lithography and high-resolution printing of DN (covalent and ionic) hydrogels within minutes. The ability to shape tough and stretchable DN hydrogels in complex structures will be potentially useful in a broad range of applications.

Injectable hydrogel based on dialdehyde galactomannan and N-succinyl chitosan: a suitable platform for cell culture.

Regenerative medicine proposes to regenerate or even replace human damaged tissues to return to normal functions. Hence, biomaterials have been used to provide appropriate environment for cell development. Among the groups of biodegradable biomaterials, hydrogels, which are characterized by three-dimensional and cross-linked networks of water-soluble polymers, have been highlighted as suitable matrices for such applications. An injectable hydrogel based on oxidized galactomannan (OxGM) from Delonix regia and N-succinyl chitosan (NSC) was developed and characterized according to its physicochemical and biocompatible properties. The hydrogel was formed by Schiff base (-CH = N-) cross-linking between aldehyde groups from OxGM and NH2 groups from NSC, in few minutes (9.7 min) without any external stimulus. A hydrogel with macroporous structure, interconnected pores, and porosity of 69% was obtained. The biomaterial exhibited excellent injectability. No change in volume or integrity was observed in the hydrogel after its swelling in phosphate buffered saline (PBS) medium. This is an important property because when the hydrogel is injected into the site of interest and it fills the environment, it will not have additional space to occupy. Biocompatibility studies were conducted in vitro, which revealed the non-cytotoxic nature of the material and demonstrated the potential of the hydrogel based on dialdehyde galactomannan and N-succinyl chitosan for cell culture and soft tissue engineering.

Comparison of Different Approaches to Surface Functionalization of Biodegradable Polycaprolactone Scaffolds.

Due to their good mechanical stability compared to gelatin, collagen or polyethylene glycol nanofibers and slow degradation rate, biodegradable poly-ε-caprolactone (PCL) nanofibers are promising material as scaffolds for bone and soft-tissue engineering. Here, PCL nanofibers were prepared by the electrospinning method and then subjected to surface functionalization aimed at improving their biocompatibility and bioactivity. For surface modification, two approaches were used: (i) COOH-containing polymer was deposited on the PCL surface using atmospheric pressure plasma copolymerization of CO2 and C2H4, and (ii) PCL nanofibers were coated with multifunctional bioactive nanostructured TiCaPCON film by magnetron sputtering of TiC–CaO–Ti3POx target. To evaluate bone regeneration ability in vitro, the surface-modified PCL nanofibers were immersed in simulated body fluid (SBF, 1×) for 21 days. The results obtained indicate different osteoblastic and epithelial cell response depending on the modification method. The TiCaPCON-coated PCL nanofibers exhibited enhanced adhesion and proliferation of MC3T3-E1 cells, promoted the formation of Ca-based mineralized layer in SBF and, therefore, can be considered as promising material for bone tissue regeneration. The PCL–COOH nanofibers demonstrated improved adhesion and proliferation of IAR-2 cells, which shows their high potential for skin reparation and wound dressing.

Architectured helically coiled scaffolds from elastomeric poly(butylene succinate) (PBS) copolyester via wet electrospinning

Electrospinning is one of the most investigated methods used to produce polymeric fiber scaffolds that mimic the morphology of native extracellular matrix. These structures have been extensively studied in the context of scaffolds for tissue regeneration. However, the compactness of materials obtained by traditional electrospinning, collected as two-dimensional non-woven scaffolds, can limit cell infiltration and tissue ingrowth. In addition, for applications in smooth muscle tissue engineering, highly elastic scaffolds capable of withstanding cyclic mechanical strains without suffering significant permanent deformations are preferred. In order to address these challenges, we report the fabrication of microscale 3D helically coiled scaffolds (referred as 3D-HCS) by wet-electrospinning method, a modification of the traditional electrospinning process in which a coagulation bath (non-solvent system for the electrospun material) is used as the collector. The present study, for the first time, successfully demonstrates the feasibility of using this method to produce various architectures of 3D helically coiled scaffolds (HCS) from segmented copolyester of poly (butylene succinate-co-dilinoleic succinate) (PBS-DLS), a thermoplastic elastomer. We examined the role of process parameters and propose a mechanism for the HCS formation. Fabricated 3D-HCS showed high specific surface area, high porosity, and good elasticity. Further, the marked increase in cell proliferation on 3D-HCS confirmed the suitability of these materials as scaffolds for soft tissue engineering.

Bioactive Glass Applications in Dentistry.

At present, researchers in the field of biomaterials are focusing on the oral hard and soft tissue engineering with bioactive ingredients by activating body immune cells or different proteins of the body. By doing this natural ground substance, tissue component and long-lasting tissues grow. One of the current biomaterials is known as bioactive glass (BAG). The bioactive properties make BAG applicable to several clinical applications involving the regeneration of hard tissues in medicine and dentistry. In dentistry, its uses include dental restorative materials, mineralizing agents, as a coating material for dental implants, pulp capping, root canal treatment, and air-abrasion, and in medicine it has its applications from orthopedics to soft-tissue restoration. This review aims to provide an overview of promising and current uses of bioactive glasses in dentistry.

Covalently injectable chitosan/chondroitin sulfate hydrogel integrated gelatin/heparin microspheres for soft tissue engineering

Microspheres and injectable hydrogels derived from natural biopolymers have been extensively investigated as drug carriers and cell scaffolds. In this study, we report a preparation of composite scaffolds basing microspheres and hydrogel via the Schiff’s base reaction. Hybrid gelatin/heparin microspheres loading insulin-like growth factor-1 (IGF-1) with a diameter of 5–10 µm were fabricated using an emulsion cross-linking method. Synchronously, water-soluble carboxymethyl chitosan (CMC) and oxidized chondroitin sulfate (OCS) were prepared for cross-linking of hydrogels, which were embedded with microspheres to produce a composite microspheres/gel scaffold. The mechanism of scaffold cross-linking is attributed to the Schiff’s base reaction between amino and aldehyde groups of biopolymers. Currently, gelation rate, morphology, mechanical properties, swelling ratio, weight loss, and IGF-1 release of the composite scaffolds were examined in vitro. The results show that mechanical and bioactive properties of CMC-OCS hydrogel can be significantly improved by embedding gelatin/heparin microspheres containing IGF-1. Compressive modulus of composite gel scaffolds containing 3 wt% of microspheres was 16 kPa, which was higher than the control hydrogel without microspheres. Cumulative release of IGF-1 during 7 days from microspheres embedded hydrogel was 70%, which was significantly lower than those of microspheres and hydrogels. Moreover, the composite microspheres/gel scaffolds exhibited higher swelling ratio and slower degradation rate than the control. Potential of the composite scaffolds was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) in vitro. Cell culture showed that this composite hydrogel could support survival and proliferation of ASCs. These results demonstrate the potential of gelatin/heparin microspheres embedded CMC-OCS hydrogels as an injectable scaffold in soft tissue engineering.

Hard Block Degradable Polycarbonate Urethanes: Promising Biomaterials for Electrospun Vascular Prostheses.

We report biodegradable thermoplastic polyurethanes for soft tissue engineering applications, where frequently used carboxylic acid ester degradation motifs were substituted with carbonate moieties to achieve superior degradation properties. While the use of carbonates in soft blocks has been reported, their use in hard blocks of thermoplastic polyurethanes is unprecedented. Soft blocks consist of poly(hexamethylene carbonate), and hard blocks combine hexamethylene diisocyanate with the newly synthesized cleavable carbonate chain extender bis(3-hydroxypropylene)carbonate (BHPC), mimicking the motif of poly(trimethylene carbonate) with highly regarded degradation properties. Simultaneously, the mechanical benefits of segmented polyurethanes are exploited. A lower hard block concentration in BHPC-based polymers was more suitable for vascular grafts. Nonacidic degradation products and hard block dependent degradation rates were found. Implantation of BHPC-based electrospun degradable vascular prostheses in a small animal model revealed high patency rates and no signs of aneurysm formations. Specific vascular graft remodeling and only minimal signs of inflammatory reactions were observed.

Functionalization and Surface Modifications of Bioactive Glasses (BGs): Tailoring of the Biological Response Working on the Outermost Surface Layer.

Bioactive glasses (BGs) are routinely being used as potent materials for hard and soft tissue engineering applications; however, improving their biological activities through surface functionalization and modification has been underestimated so far. The surface characteristics of BGs are key factors in determining the success of any implanted BG-based material in vivo since they regulate the affinity and binding of different biological macromolecules and thereby the interactions between cells and the implant. Therefore, a number of strategies using chemical agents (e.g., glutaraldehyde, silanes) and physical methods (e.g., laser treatment) have been evaluated and applied to design properly, tailor, and improve the surface properties of BGs. All these approaches aim at enhancing the biological activities of BGs, including the induction of cell proliferation and subsequent osteogenesis, as well as the inhibition of bacterial growth and adhesion, thereby reducing infection. In this study, we present an overview of the currently used approaches of surface functionalization and modifications of BGs, along with discussing the biological outputs induced by these changes.

The effect of porous structure on the cell proliferation, tissue ingrowth and angiogenic properties of poly(glycerol sebacate urethane) scaffolds.

Novel, porous, biodegradable biomaterials which support tissue integration and angiogenesis and which have elastomeric properties are needed to repair and replace soft tissues in dynamic environments. In this study poly(glycerol sebacate urethane) (PGSU) scaffolds with different porous structures were fabricated using freeze-drying by varying the polymer concentration of the freeze-drying solution, during which the polymer was further crosslinked. The effect of the porous structure on the physical properties, cell proliferation, tissue ingrowth and angiogenic properties was investigated. By increasing the polymer concentration in the freeze-drying solution from 5 w/v% to 10 w/v% and 15 w/v%, the porosity and pore size of the scaffold decreased, resulting in porosities ranging between 88 - 96% and pore sizes 6.4-28.2 μm. The mechanical properties increased with the polymer concentration, with ultimate tensile strength and Young's modulus between 0.05 - 0.86 MPa and 0.05-0.65 MPa respectively and negligible loss of tensile strength after 100 cycles of loading. Enzymatic degradation over 28 days demonstrated linear degradation kinetics with mass loss between 19.1 - 52.3%. All PGSU scaffolds provided a viable environment for cell attachment, in which cell metabolic activity increased over time indicating cell proliferation. The cells adhered to PGSU scaffolds produced and deposited high quantities of collagen, reaching 7.5% of the sample's dry mass after 14 days culture for the scaffold with the highest porosity. Additionally, the scaffolds with the polymer concentration of 5 w/v% implanted onto the chick chorioallantoic membrane supported rapid tissue ingrowth and new blood vessel formation within the porous scaffold. These results demonstrate that PGSU scaffolds have potential for use in many areas of soft tissue engineering.

Digital Design and Automated Fabrication of Bespoke Collagen Microfiber Scaffolds.

A great variety of natural and synthetic polymer materials have been utilized in soft tissue engineering as extracellular matrix (ECM) materials. Natural polymers, such as collagen and fibrin hydrogels, have experienced especially broad adoption due to the high density of cell adhesion sites compared to their synthetic counterparts, ready availability, and ease of use. However, these and other hydrogels lack the structural and mechanical anisotropy that define the ECM in many tissues, such as skeletal and cardiac muscle, tendon, and cartilage. Herein, we present a facile, low-cost, and automated method of preparing collagen microfibers, organizing these fibers into precisely controlled mesh designs, and embedding these meshes in a bulk hydrogel, creating a composite biomaterial suitable for a wide variety of tissue engineering and regenerative medicine applications. With the assistance of custom software tools described herein, mesh patterns are designed by a digital graphical user interface and translated into protocols that are executed by a custom mesh collection and organization device. We demonstrate a high degree of precision and reproducibility in both fiber and mesh fabrication, evaluate single fiber mechanical properties, and provide evidence of collagen self-assembly in the microfibers under standard cell culture conditions. This work offers a powerful, flexible platform for the study of tissue engineering and cell material interactions, as well as the development of therapeutic biomaterials in the form of custom collagen microfiber patterns that will be accessible to all through the methods and techniques described here.Impact StatementCollagen microfiber meshes have immediate and broad applications in tissue engineering research and show high potential for later use in clinical therapeutics due to their compositional similarities to native extracellular matrix and tunable structural and mechanical characteristics. Physical and biological characterizations of these meshes demonstrate physiologically relevant mechanical properties, native-like collagen structure, and cytocompatibility. The methods presented herein not only describe a process through which custom collagen microfiber meshes can be fabricated but also provide the reader with detailed device plans and software tools to produce their own bespoke meshes through a precise, consistent, and automated process.

Silk fibroin for skin injury repair: Where do things stand?

Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradability, tunable mechanical properties, aqueous preparation, minimal inflammation in host tissue, low cost and ease of use. Silk fibroin is often used alone or in combination with other materials in various formats and is also a promising delivery system for bioactive compounds as part of such repair scenarios. These properties make silk fibroin an excellent biomaterial for skin tissue engineering and repair applications. This review focuses on the promising characteristics and recent advances in the use of silk fibroin for skin wound healing and/or soft-tissue repair applications. The benefits and limitations of silk fibroin as a scaffolding biomaterial in this context are also discussed. STATEMENT OF SIGNIFICANCE: Silk protein fibroin is a natural biomaterial with important biological and mechanical properties for soft tissue engineering applications. Silk fibroin is obtained from silkworms and can be purified using alkali or enzyme based degumming (removal of glue protein sericin) procedures. Fibroin is used alone or in combination with other materials in different scaffold forms, such as nanofibrous mats, hydrogels, sponges or films tailored for specific applications. The investigations carried out using silk fibroin or its blends in skin tissue engineering have increased dramatically in recent years due to the advantages of this unique biomaterial. This review focuses on the promising characteristics of silk fibroin for skin wound healing and/or soft-tissue repair applications.

Tunable methacrylated hyaluronic acid-based hydrogels as scaffolds for soft tissue engineering applications.

Hyaluronic acid (HA)-based biomaterials have been explored for a number of applications in biomedical engineering, particularly as tissue regeneration scaffolds. Crosslinked forms of HA are more robust and provide tunable mechanical properties and degradation rates that are critical in regenerative medicine; however, crosslinking modalities reported in the literature vary and there are few comparisons of different scaffold properties for various crosslinking approaches. In this study, we offer direct comparison of two methacrylation techniques for HA (glycidyl methacrylate HA [GMHA] or methacrylic anhydride HA [MAHA]). The two methods for methacrylating HA provide degrees of methacrylation ranging from 2.4 to 86%, reflecting a wider range of properties than is possible using only a single methacrylation technique. We have also characterized mechanical properties for nine different tissues isolated from rat (ranging from lung at the softest to muscle at the stiffest) using indentation techniques and show that we can match the full range of mechanical properties (0.35-6.13 kPa) using either GMHA or MAHA. To illustrate utility for neural tissue engineering applications, functional hydrogels with adhesive proteins (either GMHA or MAHA base hydrogels with collagen I and laminin) were designed with effective moduli mechanically matched to rat sciatic nerve (2.47 ± 0.31 kPa). We demonstrated ability of these hydrogels to support three-dimensional axonal elongation from dorsal root ganglia cultures. Overall, we have shown that methacrylated HA provides a tunable platform with a wide range of properties for use in soft tissue engineering.

Recent advances in biomaterials for 3D scaffolds: A review

Considering the advantages and disadvantages of biomaterials used for the production of 3D scaffolds for tissue engineering, new strategies for designing advanced functional biomimetic structures have been reviewed. We offer a comprehensive summary of recent trends in development of single- (metal, ceramics and polymers), composite-type and cell-laden scaffolds that in addition to mechanical support, promote simultaneous tissue growth, and deliver different molecules (growth factors, cytokines, bioactive ions, genes, drugs, antibiotics, etc.) or cells with therapeutic or facilitating regeneration effect. The paper briefly focuses on divers 3D bioprinting constructs and the challenges they face. Based on their application in hard and soft tissue engineering, in vitro and in vivo effects triggered by the structural and biological functionalized biomaterials are underlined. The authors discuss the future outlook for the development of bioactive scaffolds that could pave the way for their successful imposing in clinical therapy.