Candidate Biomaterials Research Articles

Chiral nanomaterials in tissue engineering.

Addressing significant medical challenges arising from tissue damage and organ failure, the field of tissue engineering has evolved to provide revolutionary approaches for regenerating functional tissues and organs. This involves employing various techniques, including the development and application of novel nanomaterials. Among them, chiral nanomaterials comprising non-superimposable nanostructures with their mirror images have recently emerged as innovative biomaterial candidates to guide tissue regeneration due to their unique characteristics. Chiral nanomaterials including chiral fibre supramolecular hydrogels, polymer-based chiral materials, self-assembling peptides, chiral-patterned surfaces, and the recently developed intrinsically chiroptical nanoparticles have demonstrated remarkable ability to regulate biological processes through routes such as enantioselective catalysis and enhanced antibacterial activity. Despite several recent reviews on chiral nanomaterials, limited attention has been given to the specific potential of these materials in facilitating tissue regeneration processes. Thus, this timely review aims to fill this gap by exploring the fundamental characteristics of chiral nanomaterials, including their chiroptical activities and analytical techniques. Also, the recent advancements in incorporating these materials in tissue engineering applications are highlighted. The review concludes by critically discussing the outlook of utilizing chiral nanomaterials in guiding future strategies for tissue engineering design.

Structural, rheological properties and antioxidant activities analysis of the exopolysaccharide produced by Rhizobium leguminosarum bv. viciae VF39

Microbial exopolysaccharide is an eco-friendly and non-toxic biopolymeric materials widely used in various industrial fields such as pharmaceutical, food and cosmetics based on its structural, rheological and physiochemical properties. A microbial exopolysaccharide (VF39-EPS) was directly isolated from Rhizobium leguminosarum bv. viciae VF39. Structural analysis using FTIR and 2D NMR spectroscopy confirmed the complete chemical structures of VF39-EPS as 3-hydroxybutanoylglycan with octasaccharide repeating units containing two pyruvyl, two acetyl, and one 3-hydroxybutanoyl group. VF39-EPS exhibited thermal stability up to 275 °C and showed characteristic rheological behaviors of structural fluid with weak gel-like properties above 4 % the aqueous solution, suggesting VF39-EPS as a potential effective thickener or hydrogel scaffolder. Flow behavior tests validated broad stability at a wide range of both pHs from 2 to 12 and temperatures from 25 to 75 °C, and even in the presence of various salts. Furthermore, VF39-EPS showed excellent antioxidant effects of 78.5 and 62.4 % (n = 3, p < 0.001) in DPPH scavenging activity and hydroxyl radical scavenging activity, respectively. Therefore, those structural, rheological and antioxidant properties suggest that VF39-EPS could be one of the excellent biomaterial candidates for cosmetic, food and pharmaceutical industries based on its characteristic rheological behaviors in various condition and excellent antioxidant activity.

Preparation of Cholesterol-Modified Hyaluronic Acid Nanogel-Based Hydrogel and the Inflammatory Evaluation Using Macrophage-like Cells.

Nanogels are candidate biomaterials for tissue engineering and drug delivery. In the present study, a cholesterol-hyaluronic acid hydrogel was developed, and the pro-inflammatory response of macrophages to the hydrogel was investigated to determine its use in biomedical applications. Hyaluronic acid modified with cholesterol (modification rate: 0-15%) and maleimide (Chol-HA) was synthesized. The Chol-HA nanogel was formed through self-assembly via hydrophobic cholesterol interactions in aqueous solution. The Chol-HA hydrogel was formed through chemical crosslinking of the Chol-HA nanogel via a Michael addition reaction between the maleimide and thiol groups of 4arm-PEGSH. We found that the Chol-HA hydrogels with 5, 10, and 15% cholesterol inhibited the pro-inflammatory response of HiBiT-THP-1 cells, suggesting that the cholesterol contributed to the macrophage response. Furthermore, Interleukin 4 (IL-4) encapsulated in the hydrogel of the Chol-HA nanogel enhanced the inhibition of the inflammatory response in HiBiT-THP-1 cells. These results provide useful insights into the biomedical applications of hydrogels.

Unprecedented Benzoquinone Motifs Reveal Post-Oligomerizational Modification of Proanthocyanidins.

Proanthocyanidins (PACs) are complex flavan-3-ol polymers with stunning chemical complexity due to oxygenation patterns, oxidative phenolic ring linkages, and intricate stereochemistry of their heterocycles and inter-flavan linkages. Being promising candidates for dental restorative biomaterials, trace analysis of dentin bioactive cinnamon PACs now yielded novel trimeric (1 and 2) and tetrameric (3) PACs with unprecedented o- and p-benzoquinone motifs (benzoquinonoid PACs). Challenges in structural characterization, especially their absolute configuration, prompted the development of a new synthetic-analytical approach involving comprehensive spectroscopy, including NMR with quantum mechanics-driven 1H iterative functionalized spin analysis (HifSA) plus experimental and computational electronic circular dichroism (ECD). Vital stereochemical information was garnered from synthesizing 4-(2,5-benzoquinone)flavan-3-ols and a truncated analogue of trimer 2 as ECD models. Discovery of the first natural benzoquinonoid PACs provides new evidence to the experimentally elusive PAC biosynthesis as their formation requires two oxidative post-oligomerizational modifications (POMs) that are distinct and occur downstream from both quinone-methide-driven oligomerization and A-type linkage formation. While Nature is known to achieve structural diversity of many major compound classes by POMs, this is the first indication of PACs also following this common theme.

SiO2/SiC Nanowire Surfaces as a Candidate Biomaterial for Bone Regeneration

Tissue engineering (TE) and nanomedicine require devices with hydrophilic surfaces to better interact with the biological environment. This work presents a study on the wettability of cubic silicon-carbide-based (SiC) surfaces. We developed four cubic silicon-carbide-based epitaxial layers and three nanowire (NW) substrates. Sample morphologies were analyzed, and their wettabilities were quantified before and after a hydrogen plasma treatment to remove impurities due to growth residues and enhance hydrophilicity. Moreover, sample biocompatibility has been assessed with regard to L929 cells. Our results showed that core–shell nanowires (SiO2/SiC NWs), with and without hydrogen plasma treatment, are the most suitable candidate material for biological applications due to their high wettability that is not influenced by specific treatments. Biological tests underlined the non-toxicity of the developed biomaterials with regard to murine fibroblasts, and the proliferation assay highlighted the efficacy of all the surfaces with regard to murine osteoblasts. In conclusion, SiO2/SiC NWs offer a suitable substrate to develop platforms and membranes useful for biomedical applications in tissue engineering due to their peculiar characteristics.

Preparation and characterization of propolis reinforced eggshell membrane/ GelMA composite hydrogel for biomedical applications

Gelatin methacrylate-based hydrogels (GelMA) were widely used in tissue engineering and regenerative medicine. However, to manipulate their various chemical and physical properties and create high-efficiency hydrogels, different materials have been used in their structure. Eggshell membrane (ESM) and propolis are two nature-derived materials that could be used to improve the various characteristics of hydrogels, especially structural and biological properties. Hence, the main purpose of this study is the development of a new type of GelMA hydrogel containing ESM and propolis, for use in regenerative medicine. In this regard, in this study, after synthesizing GelMA, the fragmented ESM fibers were added to it and the GM/EMF hydrogel was made using a photoinitiator and visible light irradiation. Finally, GM/EMF/P hydrogels were prepared by incubating GM/EMF hydrogels in the propolis solution for 24 h. After various structural, chemical, and biological characterizations, it was found that the hydrogels obtained in this study offer improved morphological, hydrophilic, thermal, mechanical, and biological properties. The developed GM/EMF/P hydrogel presented more porosity with smaller and interconnected pores compared to the other hydrogels. GM/EMF hydrogels due to possessing EMF showed compressive strength up to 25.95 ± 1.69 KPa, which is more than the compressive strength provided by GM hydrogels (24.550 ± 4.3 KPa). Also, GM/EMF/P hydrogel offered the best compressive strength (44.65 ± 3.48) due to the presence of both EMF and propolis. GM scaffold with a contact angle of about 65.41 ± 2.199 θ showed more hydrophobicity compared to GM/EMF (28.67 ± 1.58 θ), and GM/EMF/P (26.24 ± 0.73 θ) hydrogels. Also, the higher swelling percentage of GM/EMF/P hydrogels (343.197 ± 42.79) indicated the high capacity of this hydrogel to retain more water than other scaffolds. Regarding the biocompatibility of the fabricated structures, MTT assay results showed that GM/EMF/P hydrogel significantly (p-value < 0.05) supported cell viability. Based on the results, it seems that GM/EMF/P hydrogel could be a promising biomaterial candidate for use in various fields of regenerative medicine.

Hierarchically porous bioceramics based on geopolymer-hydroxyapatite composite as a novel biomaterial: Structure, mechanical properties and biocompatibility evaluation

In this study, open-cell porous bioceramics based on geopolymers were synthesized by the replica technique. The composition consisted of a mixture of metakaolin (MK) and hydroxyapatite (HA) that combined are suitable for application in bone tissue engineering. Metakaolin is a cheap natural aluminosilicate known for its mechanical properties, while hydroxyapatite stands out for its biocompatibility due to the chemical structure similar to the bone matrix. After undergoing heat treatment (HT), the geopolymer-hydroxyapatite (GMK-HA) synthesized materials, referred to as GMK-HA-HT, presented pores in the range from 1 to 5 mm. In the compressive strength tests, they exhibited values between 1.18 and 2.9 MPa. These ranges of values signify a proper balance between mechanical strength and porosity. X-ray diffraction analysis showed phosphate and/or calcium crystalline phases in all heat-treated samples, indicating HA's successful incorporation in the geopolymer structure. In vitro tests using human adipose-derived mesenchymal stem cells (ADSCs) were conducted to evaluate the biocompatibility of the synthesized materials. The extracts obtained from the GMK-HA-HT were found to be non-cytotoxic. ADSCs in contact with extracts have no morphological changes and when cultured on the GMK-HA-HT surface, the cells interacted with the scaffold and formed a monolayer. Here, for the first time, we provide insights into this new class of materials as a promising biomaterial candidate which could be associated with ADSCs to promote bone healing.

Synthesis and Characterization of Carbonate Hydroxyapatite from &lt;i&gt;Pinctada Maxima&lt;/i&gt; Shell with Short Aging Time for Bone Biomaterial Candidate

Biomaterial products for bone repair are needed to support accelerated tissue healing. This research aimed to synthesize and characterize carbonate hydroxyapatite (CHA) from Pinctada maxima (P. maxima) using the precipitation method with a short aging time, 15 min. CHA was dried with oven-dry at 100°C for 12 h (CHA A) and a furnace-dry at 1000°C for 2 h (CHA B). Short aging time succeeded in producing CHA B-type with lattice parameters and of CHA A is 9.382 and 6.964 , while 9.451 and 6.962 for CHA B. The high temperature treatment made the diffraction peak indicating CHA more detected and crystallinity increased to 97.87%. The appearance of C–O bond and diffraction peaks of CHA verified substituted carbonates hydroxyapatite.

Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects

Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro, the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.

Promising application of a novel biomaterial, light chain of silk fibroin combined with NT3, in repairment of rat sciatic nerve defect injury

Autologous nerve transplantation is the gold standard for treating peripheral nerve defects, but it is associated with defects such as insufficient donor and secondary injury. Artificial nerve guidance conduits (NGCs) are now considered promising alternatives for bridging long nerve gaps, although exploring new biomaterials to construct NGCs remains challenging. Silk fibroin (SF) has good biocompatibility and can self-assemble in aqueous solutions. However, the lack of proximal neurotrophic factors after nerve injury is a major concern, leading to incomplete nerve regeneration. In this study, NT-3, a neurotrophin that promotes neuronal survival and differentiation, was bound to the light chain of silk fibroin (FIBL) in two ways: one was directly bound to FIBL (FIBL-NT3) and the other was a polypeptides-linker (FIBL-Linker-NT3). The design aimed to take advantage of silk fiber's character of self-assembly of heavy-light chains and test whether a flexible linker with NT3 molecule is easy to be a NT3 dimer, the active form. In vitro studies indicated that FIBL-Linker-NT3 combined with SF membranes promoted axon growth in adult rat dorsal root ganglion (DRG) neurons. Then we tested if FIBL-Linker-NT3 could self-assemble with the SF heavy chain (SFH). DTT (Dithiothreitol) was used to break the disulfide bonds between the SF light and heavy chains, and the light-chain protein was removed via dialysis. SFH was assembled using FIBL-Linker-NT3, as evidenced by the western blotting results that showed a high molecular band corresponding to SFH-FIBL-Linker-NT3. Chitosan scaffolds have been identified to provide a suitable microenvironment, so a chitosan/SF-FIBL-Linker-NT3 conduit was also constructed. Nerve transplantation of this conduit was evaluated in vivo in a rat sciatic nerve defect model. Immunohistochemical assays showed that the chitosan/SF-FIBL-Linker-NT3 group was superior to the chitosan/PBS, SF, PBS + FIBL-Linker-NT3 groups in nerve regeneration. In addition, the chitosan/SF-FIBL-Linker-NT3 conduit-transplanted group exhibited better recovery in terms of neurite length, sciatic functional index value, sensitivity to heat, time on the rotarod, wet weight ratio, cross-sectional area, compound muscle action potential, number of myelin layers, and myelin thickness in the nerve. Taking together, our study identified that FIBL-Linker-NT3 could promote axonal growth and regeneration in vivo and in vitro and is a promising candidate biomaterial for artificial NGCs.

Functionalised Hybrid Collagen-Elastin for Acellular Cutaneous Substitute Applications.

Wound contracture, which commonly happens after wound healing, may lead to physical distortion, including skin constriction. Therefore, the combination of collagen and elastin as the most abundant extracellular matrix (ECM) skin matrices may provide the best candidate biomaterials for cutaneous wound injury. This study aimed to develop a hybrid scaffold containing green natural resources (ovine tendon collagen type-I and poultry-based elastin) for skin tissue engineering. Briefly, freeze-drying was used to create the hybrid scaffolds, which were then crosslinked with 0.1% (w/v) genipin (GNP). Next, the physical characteristics (pore size, porosity, swelling ratio, biodegradability and mechanical strength) of the microstructure were assessed. Energy dispersive X-ray spectroscopy (EDX) and Fourier transform infrared (FTIR) spectrophotometry were used for the chemical analysis. The findings showed a uniform and interconnected porous structure with acceptable porosity (>60%) and high-water uptake capacity (>1200%), with pore sizes ranging between 127 ± 22 and 245 ± 35 µm. The biodegradation rate of the fabricated scaffold containing 5% elastin was lower (<0.043 mg/h) compared to the control scaffold (collagen only; 0.085 mg/h). Further analysis with EDX identified the main elements of the scaffold: it contained carbon (C) 59.06 ± 1.36-70.66 ± 2.89%, nitrogen (N) 6.02 ± 0.20-7.09 ± 0.69% and oxygen (O) 23.79 ± 0.65-32.93 ± 0.98%. FTIR analysis revealed that collagen and elastin remained in the scaffold and exhibited similar functional amides (amide A: 3316 cm-1, amide B: 2932 cm-1, amide I: 1649 cm-1, amide II: 1549 cm-1 and amide III: 1233 cm-1). The combination of elastin and collagen also produced a positive effect via increased Young's modulus values. No toxic effect was identified, and the hybrid scaffolds significantly supported human skin cell attachment and viability. In conclusion, the fabricated hybrid scaffolds demonstrated optimum physicochemical and mechanical properties and may potentially be used as an acellular skin substitute in wound management.

A comprehensive study of the impact on the microstructure and corrosion behavior of magnesium alloy-based porous bone implants

Magnesium orthopedic implants have been categorized to be one of the potential metallic biomaterial candidates due to their better biocompatibility nature, excellent biodegradability feature and its comparable mechanical properties with natural human bone. But, magnesium scaffolds experience unstable biocorrosion under physiological solutions, thus hindering their utility in implant applications. Moreover, conventional and typical metallic implants are non-porous in nature and also often result in stress shielding. To this end, this research has examined the outcome of adding metallic alloying elements (Ca, Zn and Fe) into the Mg metal matrix, while varying porosity was produced by incorporating carbamide. The corrosion behavior of the produced samples post-immersion in Hank’s solution was observed. This investigation established that the corrosion rates of the alloyed samples could be controlled by tuning the sample compositions. The corroded samples were also observed under optical microscopy, which revealed the protective layer, which could have retarded the corrosion of the immersed samples. X-ray micro-computed tomography results confirm the gradient porosity with interconnected pores in the produced samples, a vital feature for an implant. Therefore, this investigation confirms that the behavior of biocorrosion could be tailored by fabricating customized Mg-alloy-based bone implants.

Development and In Vivo Assessment of an Injectable Cross-Linked Cartilage Acellular Matrix-PEG Hydrogel Scaffold Derived from Porcine Cartilage for Tissue Engineering.

The cartilage acellular matrix (CAM) derived from porcine cartilage, which does not induce significant inflammation and provides an environment conducive for cell growth and differentiation, is a promising biomaterial candidate for scaffold fabrication. However, the CAM has a short period in vivo, and the in vivo maintenance is not controlled. Therefore, this study is aimed at developing an injectable hydrogel scaffold using a CAM. The CAM is cross-linked with a biocompatible polyethylene glycol (PEG) cross-linker to replace typically used glutaraldehyde (GA) cross-linker. The cross-linking degree of cross-linked CAM by PEG cross-linker (Cx-CAM-PEG) according to the ratios of the CAM and PEG cross-linker is confirmed by contact angle and heat capacities measured by differential scanning calorimetry. The injectable Cx-CAM-PEG suspension exhibits controllable rheological properties and injectability. Additionally, injectable Cx-CAM-PEG suspensions with no free aldehyde group are formed in the in vivo hydrogel scaffold almost simultaneously with injection. In vivo maintenance of Cx-CAM-PEG is realized by the cross-linking ratio. The in vivo formed Cx-CAM-PEG hydrogel scaffold exhibits certain host-cell infiltration and negligible inflammation within and near the transplanted Cx-CAM-PEG hydrogel scaffold. These results suggest that injectable Cx-CAM-PEG suspensions, which are safe and biocompatible in vivo, represent potential candidates for (pre-)clinical scaffolds.

Advances of Mussel-Inspired Nanocomposite Hydrogels in Biomedical Applications.

Hydrogels, with 3D hydrophilic polymer networks and excellent biocompatibilities, have emerged as promising biomaterial candidates to mimic the structure and properties of biological tissues. The incorporation of nanomaterials into a hydrogel matrix can tailor the functions of the nanocomposite hydrogels to meet the requirements for different biomedical applications. However, most nanomaterials show poor dispersion in water, which limits their integration into the hydrophilic hydrogel network. Mussel-inspired chemistry provides a mild and biocompatible approach in material surface engineering due to the high reactivity and universal adhesive property of catechol groups. In order to attract more attention to mussel-inspired nanocomposite hydrogels, and to promote the research work on mussel-inspired nanocomposite hydrogels, we have reviewed the recent advances in the preparation of mussel-inspired nanocomposite hydrogels using a variety of nanomaterials with different forms (nanoparticles, nanorods, nanofibers, nanosheets). We give an overview of each nanomaterial modified or hybridized by catechol or polyphenol groups based on mussel-inspired chemistry, and the performances of the nanocomposite hydrogel after the nanomaterial's incorporation. We also highlight the use of each nanocomposite hydrogel for various biomedical applications, including drug delivery, bioelectronics, wearable/implantable biosensors, tumor therapy, and tissue repair. Finally, the challenges and future research direction in designing mussel-inspired nanocomposite hydrogels are discussed.

Structural Characteristics and Properties of Cocoon and Regenerated Silk Fibroin from Different Silkworm Strains.

Silk has attracted the attention of researchers as a biomedical and cosmetic material because of its good biocompatibility and cytocompatibility. Silk is produced from the cocoons of silkworms, which have various strains. In this study, silkworm cocoons and silk fibroins (SFs) were obtained from ten silkworm strains, and their structural characteristics and properties were examined. The morphological structure of the cocoons depended on the silkworm strains. The degumming ratio of silk ranged from 22.8% to 28% depending on the silkworm strains. The highest and lowest solution viscosities of SF were shown by 9671 and 9153, respectively, showing a 12-fold difference. The silkworm strains of 9671, KJ5, and I-NOVI showed a two-fold higher work of ruptures for the regenerated SF film than 181 and 2203, indicating that the silkworm strains considerably influence the mechanical properties of the regenerated SF film. Regardless of the silkworm strain, all silkworm cocoons showed good cell viability, making them suitable candidates for advanced functional biomaterials.

Characterization of Cyclic Olefin Copolymers for Insulin Reservoir in an Artificial Pancreas

Type-1 diabetes is one of the most prevalent metabolic disorders worldwide. It results in a significant lack of insulin production by the pancreas and the ensuing hyperglycemia, which needs to be regulated through a tailored administration of insulin throughout the day. Recent studies have shown great advancements in developing an implantable artificial pancreas. However, some improvements are still required, including the optimal biomaterials and technologies to produce the implantable insulin reservoir. Here, we discuss the employment of two types of cyclic olefin copolymers (Topas 5013L-10 and Topas 8007S-04) for an insulin reservoir fabrication. After a preliminary thermomechanical analysis, Topas 8007S-04 was selected as the best material to fabricate a 3D-printed insulin reservoir due to its higher strength and lower glass transition temperature (Tg). Fiber deposition modeling was used to manufacture a reservoir-like structure, which was employed to assess the ability of the material to prevent insulin aggregation. Although the surface texture presents a localized roughness, the ultraviolet analysis did not detect any significant insulin aggregation over a timeframe of 14 days. These interesting results make Topas 8007S-04 cyclic olefin copolymer a potential candidate biomaterial for fabricating structural components in an implantable artificial pancreas.

In Situ Fabrication of Robust Polyphenolic Hydrogels for Skin Protection and Repair

Robust and multifunctional polyphenolic hydrogels have been well acknowledged as promising biomaterial candidates due to their various fascinating properties in regulating cell biology. However, the construction of these hydrogels commonly needs multistep fabrication and a sophisticated gelation process. The typical phenol-aldehyde condensation is a facial and in situ reaction for industrial resin construction; however, its application in hydrogel fabrication is seldom reported. In this study, we reported the feasibility and modularity of this strategy for in situ fabricating various kinds of robust and multifunctional natural polyphenolic hydrogels using natural polyphenol (extracts) and formaldehyde. The physicochemical characterization results demonstrated that the chemical structure (e.g., phenolic hydroxyl groups) of polyphenol molecules could be well maintained after the gelation process, allowing as-prepared hydrogels to inherit the merits of polyphenol molecules, such as good UV shielding, radical scavenging, antibacterial properties, and so forth, as demonstrated by in vitro data. The in vitro and in vivo cellular and animal results further confirmed that the as-prepared hydrogels were able to perform a skin protection and repair role, as demonstrated in UV protection and wound healing models. Collectively, this strategy could allow natural polyphenols as both structural and functional synthons toward more types of robust hydrogels for a wide range of biomedical applications.

Hydrogels from TEMPO-Oxidized Nanofibrillated Cellulose Support In Vitro Cultivation of Encapsulated Human Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are the most prominent type of adult stem cells for clinical applications. Three-dimensional (3D) cultivation of MSCs in biomimetic hydrogels provides a more physiologically relevant cultivation microenvironment for in vitro testing and modeling, thus overcoming the limitations of traditional planar cultivation methods. Cellulose nanofibers are an excellent candidate biomaterial for synthesis of hydrogels for this application, due to their biocompatibility, tunable properties, availability, and low cost. Herein, we demonstrate the capacity of hydrogels prepared from 2,2,6,6-tetramethylpiperidine-1-oxyl -oxidized and subsequently individualized cellulose-nanofibrils to support physiologically relevant 3D in vitro cultivation of human MSCs at low solid contents (0.2-0.5 wt %). Our results show that MSCs can spread, proliferate, and migrate inside the cellulose hydrogels, while the metabolic activity and proliferative capacity of the cells as well as their morphological characteristics benefit more in the lower bulk cellulose concentration hydrogels.

Orchestrating Chemical and Physical Cross-Linking in Protein Hydrogels to Regulate Embryonic Stem Cell Growth.

Protein hydrogels are ideal candidates for next-generation biomaterials due to their genetically programmable properties. Herein, we report an entirely protein-based hydrogel as an artificial extracellular matrix (ECM) for regulating the embryonic stem cell growth. A synergy between chemical and physical cross-linking was achieved in one step by SpyTag/SpyCatcher reaction and P zipper association at 37 °C. The hydrogels' stress relaxation behaviors can be tuned across a broad spectrum by single-point mutation on a P zipper. It has been found that faster relaxation can promote the growth of HeLa tumor spheroids and embryonic stem cells, and mechanical regulation of embryonic stem cells occurs via retention of the cells at the G1 phase. The results highlight the promise of genetically encoded protein materials as a platform of artificial ECM for understanding and controlling the complex cell-matrix interactions in a 3D cell culture.

Applications of functionally-adapted hydrogels in tendon repair.

Despite all the efforts made in tissue engineering for tendon repair, the management of tendon injuries still poses a challenge, as current treatments are unable to restore the function of tendons following injuries. Hydrogels, due to their exceptional biocompatibility and plasticity, have been extensively applied and regarded as promising candidate biomaterials in tissue regeneration. Varieties of approaches have designed functionally-adapted hydrogels and combined hydrogels with other factors (e.g., bioactive molecules or drugs) or materials for the enhancement of tendon repair. This review first summarized the current state of knowledge on the mechanisms underlying the process of tendon healing. Afterward, we discussed novel strategies in fabricating hydrogels to overcome the issues frequently encountered during the applications in tendon repair, including poor mechanical properties and undesirable degradation. In addition, we comprehensively summarized the rational design of hydrogels for promoting stem-cell-based tendon tissue engineering via altering biophysical and biochemical factors. Finally, the role of macrophages in tendon repair and how they respond to immunomodulatory hydrogels were highlighted.