Control the fate of human umbilical cord mesenchymal stem cells with dual‐enzymatically cross‐linked gelatin hydrogels for potential applications in nerve regeneration

Stem‐cell‐based therapy is a promising strategy to treat challenging neurological diseases, while its application is hindered primarily by the low viability and uncontrolled differentiation of stem cell. Hydrogel can be properly engineered to share similar characteristics with the target tissue, thus promoting cell viability and directing cell differentiation. In this study, we proposed a new dual‐enzymatically cross‐linked and injectable gelatin hydrogel for regulating survival, proliferation, and differentiation of human umbilical cord mesenchymal stem cells (hUC‐MSCs) in a three‐dimensional matrix. This injectable gelatin hydrogel was formed by oxidative coupling of gelatin–hydroxyphenyl acid conjugates catalyzed by hydrogen horseradish peroxidase (HRP) and choline oxidase (ChOx). Modulus and H₂O₂ release can be well controlled by ChOx activity. Results from calcein‐AM/PI staining and Ki67 immunofluorescence tests demonstrated that the survival and proliferation behavior of hUC‐MSCs were highly enhanced in HRP_1UChOx_0.25U hydrogel with lower modulus and less H₂O₂ release compared with other groups. Attractively, the expression of neuron‐specific markers β‐III tubulin, neurofilament light chain (NFL), and synapsin‐1 was significantly increased in HRP_1UChOx_0.25U hydrogel as well. Additionally, in vitro hemolysis test and in vivo HE staining data highlighted the good biocompatibility. Undoubtedly, this injectable gelatin hydrogel's ability to control hUC‐MSCs' fate holds enormous potentials in nervous disorders' therapy and nerve regeneration.     

Phospholipid‐induced silk fibroin hydrogels and their potential as cell carriers for tissue regeneration

Silk fibroin (SF) hydrogels can be obtained via self‐assembly, but this process takes several days or weeks, being unfeasible to produce cell carrier hydrogels. In this work, a phospholipid, namely, 1,2‐dimyristoyl‐sn‐glycero‐3‐phospho‐(1′‐rac‐glycerol) sodium salt (DMPG), was used to induce and accelerate the gelation process of SF solutions. Due to the amphipathic nature and negative charge of DMPG, electrostatic and hydrophobic interactions between the phospholipids and SF chains will occur, inducing the structural transition of SF chains to the beta sheet and consequently a rapid gel formation is observed (less than 50 min). Moreover, the gelation time can be controlled by varying the lipid concentration. To assess the potential of the hydrogels as cell carriers, several mammalian cell lines, including L929, NIH/3T3, SaOS‐2, and CaSki, were encapsulated into the hydrogel. The silk‐based hydrogels supported the normal growth of fibroblasts, corroborating their cytocompatibility. Interestingly, an inhibition in the growth of cancer‐derived cell lines was observed. Therefore, DMPG‐induced SF hydrogels can be successfully used as a 3D platform for in situ cell encapsulation, opening promising opportunities in biomedical applications, such as in cell therapies and tissue regeneration.     

Functional analysis of recombinant 2‐Cys peroxiredoxin from the hard tick Haemaphysalis longicornis

Ticks are obligate haematophagous arthropods that feed on vertebrate blood containing high levels of iron. The host‐derived iron reacts to oxygen in the tick's body, and then high levels of reactive oxygen species, including hydrogen peroxide (H₂O₂), may be generated. High levels of H₂O₂ cause oxidative stress to aerobic organisms. Therefore, antioxidant responses are necessary to control H₂O₂. We focused on peroxiredoxins (Prxs), H₂O₂‐scavenging enzymes. The sequence of Haemaphysalis longicornis 2‐Cys Prx (HlPrx2) was identified from fat body cDNA libraries of this tick and recombinant HlPrx2 was then prepared using Escherichia coli. By comparison with the 2‐Cys Prxs of other organisms, we found two conserved cysteines in HlPrx2, Cys51 and Cys172. We examined the antioxidant activity of HlPrx2 and mutant proteins produced by a single base substitution, converting one or both of these cysteines into serines. The assays revealed that proteins containing Cys51 showed antioxidant activity when H₂O₂ was removed. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and size‐exclusion chromatography demonstrated that only the wild‐type HlPrx2 formed homodimers and that all of the proteins that we made had a high molecular weight peak. These results indicate that both Cys51 and Cys172 are essential for the dimerization of HlPrx2, whereas only the Cys51 residue is necessary for antioxidant activity.     

Preparation and applications of peptide-based injectable hydrogels

In situ injectable hydrogels have shown tremendous potential application in the biomedical field due to their significant drug accumulation at lesion sites, sustained release and markedly reduced systemic side effects. Specifically, peptide-based hydrogels, with unique biodegradation, biocompatibility, and bioactivity, are attractive molecular skeletons. In addition, peptides play a prominent role in normal metabolism, mimicking the natural tissue microenvironment and responding to stimuli in the lesion environment. Their advantages endow peptide-based hydrogels with great potential for application as biomedical materials. In this review, the fabrication and production of peptide-based hydrogels are presented. Several promising candidates, which are smart and environment-sensitive, are briefly reviewed. Then, the recent developments of these hydrogels for biomedical applications in tissue engineering, as drug/gene vehicles, and anti-bacterial agents are discussed. Finally, the development of peptide-based injectable hydrogels for biomedical applications in the future is surveyed.

The recent progress of peptide-based injectable hydrogels for biomedical applications is extensively summarized.     

RGD‐mimic polyamidoamine–montmorillonite composites with tunable stiffness as scaffolds for bone tissue‐engineering applications

This paper reports on the development of montmorillonite (MMT)‐reinforced hydrogels, based on a peptidomimetic polyamidoamine carrying guanidine pendants (AGMA1), as substrates for the osteo‐induction of osteoblast precursor cells. AGMA1 hydrogels of various degrees of crosslinking responded favourably to MMT reinforcement, giving rise to composite hydrogels with shear storage modulus G′, when fully swollen in water, up to 200 kPa, i.e. 20 times higher than the virgin hydrogels and of the same order or higher than other hydrogel‐based composites proposed for orthopaedic applications. This significant improvement was ascribed to the effective interpenetration between the polymer matrix and the inorganic filler. AGMA1–MMT hydrogels, when evaluated as scaffolds for the osteogenic differentiation of mouse calvaria‐derived pre‐osteoblastic MC3T3‐E1 cells, proved able to support cell adhesion and proliferation and clearly induced differentiation towards the osteoblastic phenotype, as indicated by different markers. In addition, AGMA1–MMT hydrogels proved completely degradable in aqueous media at pH 7.4 and did not provide any evidence of cytotoxicity. The experimental evidence suggests that AGMA1–MMT composites definitely warrant potential as scaffolds for osteoblast culture and bone grafts. Copyright © 2016 John Wiley & Sons, Ltd.     

Enzymatic,urease‐mediated mineralization of gellan gum hydrogel with calcium carbonate,magnesium‐enriched calcium carbonate and magnesium carbonate for bone regeneration applications

Mineralization of hydrogel biomaterials is considered desirable to improve their suitability as materials for bone regeneration. Calcium carbonate (CaCO₃) has been successfully applied as a bone regeneration material, but hydrogel‐CaCO₃ composites have received less attention. Magnesium (Mg) has been used as a component of calcium phosphate biomaterials to stimulate bone‐forming cell adhesion and proliferation and bone regeneration in vivo, but its effect as a component of carbonate‐based biomaterials remains uninvestigated. In the present study, gellan gum (GG) hydrogels were mineralized enzymatically with CaCO₃, Mg‐enriched CaCO₃ and magnesium carbonate to generate composite biomaterials for bone regeneration. Hydrogels loaded with the enzyme urease were mineralized by incubation in mineralization media containing urea and different ratios of calcium and magnesium ions. Increasing the magnesium concentration decreased mineral crystallinity. At low magnesium concentrations calcite was formed, while at higher concentrations magnesian calcite was formed. Hydromagnesite (Mg₅(CO₃)₄(OH)₂.4H₂O) formed at high magnesium concentration in the absence of calcium. The amount of mineral formed and compressive strength decreased with increasing magnesium concentration in the mineralization medium. The calcium:magnesium elemental ratio in the mineral formed was higher than in the respective mineralization media. Mineralization of hydrogels with calcite or magnesian calcite promoted adhesion and growth of osteoblast‐like cells. Hydrogels mineralized with hydromagnesite displayed higher cytotoxicity. In conclusion, enzymatic mineralization of GG hydrogels with CaCO₃ in the form of calcite successfully reinforced hydrogels and promoted osteoblast‐like cell adhesion and growth, but magnesium enrichment had no definitive positive effect. Copyright © 2017 John Wiley & Sons, Ltd.     

Biocompatibility of two model elastin‐like recombinamer‐based hydrogels formed through physical or chemical cross‐linking for various applications in tissue engineering and regenerative medicine

Biocompatibility studies, especially innate immunity induction, in vitro and in vivo cytotoxicity, and fibrosis, are often lacking for many novel biomaterials including recombinant protein‐based ones, such as elastin‐like recombinamers (ELRs), and has not been extensively explored in the scientific literature, in contrast to traditional biomaterials. Herein, we present the results from a set of experiments designed to elucidate the preliminary biocompatibility of 2 types of ELRs that are able to form extracellular matrix‐like hydrogels through either physical or chemical cross‐linking both of which are intended for different applications in tissue engineering and regenerative medicine. Initially, we present in vitro cytocompatibility results obtained upon culturing human umbilical vein endothelial cells on ELR substrates, showing optimal proliferation up to 9 days. Regarding in vivo cytocompatibility, luciferase‐expressing hMSCs were viable for at least 4 weeks in terms of bioluminescence emission when embedded in ELR hydrogels and injected subcutaneously into immunosuppressed mice. Furthermore, both types of ELR‐based hydrogels were injected subcutaneously in immunocompetent mice and serum TNFα, IL‐1β, IL‐4, IL‐6, and IL‐10 concentrations were measured by enzyme‐linked immunosorbent assay, confirming the lack of inflammatory response, as also observed upon macroscopic and histological evaluation. All these findings suggest that both types of ELRs possess broad biocompatibility, thus making them very promising for tissue engineering and regenerative medicine‐related applications.     

Biological evaluation of intervertebral disc cells in different formulations of gellan gum‐based hydrogels

Gellan gum (GG)‐based hydrogels are advantageous in tissue engineering not only due to their ability to retain large quantities of water and provide a similar environment to that of natural extracellular matrix (ECM), but also because they can gelify in situ in seconds. Their mechanical properties can be fine‐tuned to mimic natural tissues such as the nucleus pulposus (NP). This study produced different formulations of GG hydrogels by mixing varying amounts of methacrylated (GG‐MA) and high‐acyl gellan gums (HA‐GG) for applications as acellular and cellular NP substitutes. The hydrogels were physicochemically characterized by dynamic mechanical analysis. Degradation and swelling abilities were assessed by soaking in a phosphate buffered saline solution for up to 170 h. Results showed that as HA‐GG content increased, the modulus of the hydrogels decreased. Moreover, increases in HA‐GG content induced greater weight loss in the GG‐MA/HA‐GG formulation compared to GG‐MA hydrogel. Potential cytotoxicity of the hydrogel was assessed by culturing rabbit NP cells up to 7 days. An MTS assay was performed by seeding rabbit NP cells onto the surface of 3D hydrogel disc formulations. Viability of rabbit NP cells encapsulated within the different hydrogel formulations was also evaluated by Calcein‐AM and ATP assays. Results showed that tunable GG‐MA/HA‐GG hydrogels were non‐cytotoxic and supported viability of rabbit NP cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Adipose tissue engineering using adipose‐derived stem cells enclosed within an injectable carboxymethylcellulose‐based hydrogel

In situ gelation of an aqueous solution of carboxymethylcellulose derivative bearing phenolic hydroxyl groups (CMC‐Ph) that contained suspended adipose‐derived stem cells (ASCs) was studied in vitro and in vivo for evaluating feasibility in adipose tissue‐engineering strategies. The rat ASCs that were enclosed in the CMC‐Ph gels through a horseradish peroxidase‐catalysed reaction showed 92.8% viability, good proliferation and adipogenic differentiation in vitro. Ten weeks after the subcutaneous injection of ASCs‐suspending CMC‐Ph for in situ gelation, clearly visible new vascularized adipose tissue formed at the injection site. The number of blood vessels and the area occupied by adipose tissues were five and eight times larger, respectively, than those found in the implanted acellular gel. The adipogenesis and neovascularization were further enhanced by incorporation of fibroblast growth factor into the CMC‐Ph gel containing ASCs. Copyright © 2012 John Wiley & Sons, Ltd.     

Incorporation of magnesium ions into photo‐crosslinked alginate hydrogel enhanced cell adhesion ability

Photo‐crosslinked alginate hydrogel attracts wide interest in tissue engineering because of its excellent controllability and stability. However, its highly hydrophilic property makes cell adhesion difficult. Plenty of studies have confirmed that magnesium ions (Mg²⁺) can efficiently improve the attachment of osteoblasts. In this study, for the first time, we fabricated a durable, crosslinked, alginate hydrogel with a dual‐crosslinking network. Photo‐crosslinked alginate hydrogel was chosen as the basic backbone, and various amounts of Mg²⁺ were incorporated into the hydrogel through ionic crosslinking. The results showed that the physicochemical properties of the hydrogels, including surface structure, composition, swelling ratio, ion release and elastic modulus, could be well tuned by controlling the amount of Mg²⁺ incorporated. In addition, a certain amount of Mg²⁺ significantly improved the attachment and spread of osteoblasts on the hydrogels. These characteristics make Mg²⁺‐incorporated photo‐crosslinked alginate hydrogel a promising scaffold for bone tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.     

Chondrogenic potential of injectable κ‐carrageenan hydrogel with encapsulated adipose stem cells for cartilage tissue‐engineering applications

Due to the limited self‐repair capacity of cartilage, regenerative medicine therapies for the treatment of cartilage defects must use a significant amount of cells, preferably applied using a hydrogel system that can promise their delivery and functionality at the specific site. This paper discusses the potential use of κ‐carrageenan hydrogels for the delivery of stem cells obtained from adipose tissue in the treatment of cartilage tissue defects. The developed hydrogels were produced by an ionotropic gelation method and human adipose stem cells (hASCs) were encapsulated in 1.5% w/v κ‐carrageenan solution at a cell density of 5 × 10⁶ cells/ml. The results from the analysis of the cell‐encapsulating hydrogels, cultured for up to 21 days, indicated that κ‐carrageenan hydrogels support the viability, proliferation and chondrogenic differentiation of hASCs. Additionally, the mechanical analysis demonstrated an increase in stiffness and viscoelastic properties of κ‐carrageenan gels with their encapsulated cells with increasing time in culture with chondrogenic medium. These results allowed the conclusion that κ‐carrageenan exhibits properties that enable the in vitro functionality of encapsulated hASCs and thus may provide the basis for new successful approaches for the treatment of cartilage defects. Copyright © 2013 John Wiley & Sons, Ltd.     

Immunodetection of a brown planthopper (Nilaparvata lugens Stål) salivary catalase‐like protein into tissues of rice,Oryza sativa

Saliva plays an important role in host plant–phloem‐feeding insect molecular interactions. To better elucidate the role of insect saliva, a series of experiments were conducted to establish if catalase from the salivary glands of the brown planthopper (BPH; Nilaparvata lugens Stål) was secreted into rice host plant tissue during feeding. Catalase is the main enzyme that decomposes hydrogen peroxide (H₂O₂) at high concentrations. H₂O₂ is a part of the free radicals system that mediates important physiological roles including signalling and defence. Previous studies have suggested that H₂O₂ is involved in the rice endogenous response to BPH feeding. If, the BPH secretes catalase into host plant tissue this will counter the effects of H₂O₂, from detoxification to interfering with plant signalling and defence mechanisms. When BPHs were fed on a hopper‐resistant rice variety for 24 h, catalase activity in the salivary glands increased 3.5‐fold compared with hoppers fed on a susceptible rice variety. Further supporting evidence of the effects of BPH catalase was demonstrated by immunodetection analyses where results from two independent sources: BPH‐infested rice tissue and BPH‐probed artificial diets, suggest that the BPH secretes catalase‐like protein during feeding. The possible physiological roles of BPH‐secreted catalase are discussed.     

P(NIPAAM–co‐HEMA) thermoresponsive hydrogels: an alternative approach for muscle cell sheet engineering

Loss of skeletal muscle tissue caused by traumatic injury or damage due to myopathies produces a deficit of muscle function for which there is still no clinical treatment. Transplantation of myogenic cells, themselves or combined with materials, has been proposed to increase the regenerative capacity of skeletal muscle but it is hampered by many limitations, such as low cell survival and engraftment or immunological reaction and low biocompatibility of the exogenous materials. Recently, myoblast sheet engineering, obtained with thermoresponsive culture dishes, has attracted attention as a new technique for muscle damage treatment. For this purpose, a series of thermoresponsive hydrogels, constituted by poly(N‐isopropylacrylamide‐co‐2‐hydroxyethylmethacrylate) [p(NIPAAM‐co‐HEMA)] were synthesized by a simple and inexpensive free‐radical polymerization of the two co‐monomers with a redox initiator. Different ratios of N‐isopropylacrylamide (NIPAAm) and 2‐hydroxyethylmethacrylate (HEMA) have been examined to evaluate the effects on physicochemical, mechanical and optical hydrogel properties. The murine muscle cell line C₂C₁₂ has been exploited to test the cytotoxicity of the thermoresponsive hydrogels, depending on different synthesis conditions. In this study, we have identified a thermoresponsive hydrogel that allows cell adhesion and viability, together with the detachment of viable sheet of muscle cells, giving the chance to develop further applications for muscle damage and disease. Copyright © 2014 John Wiley & Sons, Ltd.     

Positive MRI contrast enhancement in THP‐1 cells with Gd2O3 nanoparticles

There is a demand for more efficient and tissue‐specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd₂O₃) have been investigated for cell labeling and capacity to generate a positive contrast. THP‐1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd₂O₃‐labeled cells have shorter T₁ and T₂ relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd₂O₃ nanoparticles can be used as a positive contrast agent for cell labeling. The r₁ for cell samples was 4.1 and 3.6 s^?1 mm ^?1 for cell culture medium. The r₂ was 17.4 and 12.9 s^?1 mm ^?1, respectively. For r₁, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (p_r1 = 0.36), but r₂ was significantly different for the two different series (p_r2 = 0.02). Viability results indicate that THP‐1 cells endure treatment with Gd₂O₃ nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells. Copyright © 2008 John Wiley & Sons, Ltd.     

Gelatin methacryloyl (GelMA)-based biomaterials for bone regeneration

Gelatin methacryloyl (GelMA)-based biomaterials have been widely used in various biomedical applications due to their suitable biological properties and tuneable physical characteristics. In particular, GelMA can be used as a versatile matrix for bone tissue engineering scaffolds via various strategies to overcome major obstacles such as insufficient mechanical property and uncontrollable degradation. This review presents the research status of GelMA, its structure and function, GelMA-based biomaterials and the development of methods along with their existing challenges.

Gelatin methacryloyl (GelMA) and its based hydrogels have been widely used in various biomedical applications.     

Microwave‐assisted fabrication of chitosan–hydroxyapatite superporous hydrogel composites as bone scaffolds

In this study, a novel scaffold fabrication method was developed by combining microwave irradiation and gas foaming. Chitosan superporous hydrogels (SPHs) and chitosan–hydroxyapatite (HA) superporous hydrogel composites (SPHCs) were prepared by using this method in the presence of crosslinking agent, glyoxal, and a gas‐blowing agent, NaHCO₃. In order to examine the effect of HA on composite structure and cellular behaviour, two types of HA particles, i.e. spherical beads in 45–80 µm diameter and powder form, were used. While rapid heating with microwave irradiation enhances gas blowing, pH increment, which is accelerated by NaHCO₃ decomposition, provides better crosslinking. Thus, interconnected and well‐established macroporous hydrogels/hydrogel composites were produced easily and rapidly (~1 min). Cell culture studies, which were carried out under static and dynamic conditions with MC3T3‐E1 pre‐osteoblastic cells, indicated that chitosan–HA bead SPHCs supported cellular proliferation and osteoblastic differentiation better than chitosan SPHs and chitosan–HA powder SPHCs. In conclusion, simultaneous gas foaming and microwave crosslinking can be evaluated for the preparation of composite scaffolds which have superior properties for bone tissue engineering. Copyright © 2012 John Wiley & Sons, Ltd.     

A laminin‐2‐derived peptide promotes early‐stage peripheral nerve regeneration in a dual‐component artificial nerve graft

The DLTIDDSYWYRI motif (Ln2‐P3) of human laminin‐2 has been reported to promote PC12 cell attachment through syndecan‐1; however, the in vivo effects of Ln2‐P3 have not been studied. In Schwann cells differentiated from skin‐derived precursors, the peptide was effective in promoting cell attachment and spreading in vitro. To examine the effects of Ln2‐P3 in peripheral nerve regeneration in vivo, we developed a dual‐component poly(p‐dioxanone) (PPD)/poly(lactic‐co‐glycolic acid) (PLGA) artificial nerve graft. The novel graft was coated with scrambled peptide or Ln2‐P3 and used to bridge a 10 mm defect in rat sciatic nerves. The dual‐component nerve grafts provided tensile strength comparable to that of a real rat nerve trunk. The Ln2‐P3‐treated grafts promoted early‐stage peripheral nerve regeneration by enhancing the nerve regeneration rate and significantly increased the myelinated fibre density compared with scrambled peptide‐treated controls. These findings indicate that Ln2‐P3, combined with tissue‐engineering scaffolds, has potential biomedical applications in peripheral nerve injury repair. Copyright © 2012 John Wiley & Sons, Ltd.     

Ex vivo expansion of cord blood haematopoietic stem/progenitor cells under physiological oxygen tensions: clear‐cut effects on cell proliferation,differentiation and metabolism

Physiologically low O₂ tensions are believed to regulate haematopoietic stem cell (HSC) functions in the bone marrow (BM; 0–5%). In turn, placenta and umbilical cord are characterized by slightly higher physiological O₂ tensions (3–10%). We hypothesized that O₂ concentrations within this range may be exploited to augment the ex vivo expansion/maintenance of HSCs from umbilical cord (placental) blood (UCB). The expansion of UCB CD34⁺‐enriched cells was studied in co‐culture with BM mesenchymal stem/stromal cells (MSCs) under 2%, 5%, 10% and 21% O₂. 2% O₂ resulted in a significantly lower CD34⁺ cell expansion (25‐fold vs 60‐, 64‐ and 92‐fold at day 10 for 5%, 21%, 10% O₂, respectively). In turn, 10% O₂ promoted the highest CD34⁺CD90⁺ cell expansion, reaching 22 ± 5.4‐ vs 5.6 ± 2.4‐ and 5.7 ± 2.0‐fold for 2%, 5% and 21% O₂, respectively, after 14 days. Similar differentiation patterns were observed under different O₂ tensions, being primarily shifted towards the neutrophil lineage. Cell division kinetics revealed a higher proliferative status of cells cultured under 10% and 21% vs 2% O₂. Expectedly, higher specific glucose consumption and lactate production rates were determined at 2% O₂ when compared to higher O₂ concentrations (5–21%). Overall, these results suggest that physiological oxygen tensions, in particular 10% O₂, can maximize the ex vivo expansion of UCB stem/progenitor cells in co‐culture with BM MSCs. Importantly, these studies highlight the importance of exploiting knowledge of the intricate microenvironment of the haematopoietic niche towards the definition of efficient and controlled ex vivo culture systems capable of generating large HSCs numbers for clinical applications. Copyright © 2013 John Wiley & Sons, Ltd.     

Sustained release of parathyroid hormone via in situ cross‐linking gelatin hydrogels improves the therapeutic potential of tonsil‐derived mesenchymal stem cells for hypoparathyroidism

Biomimetic parathyroid regeneration with sustained release of parathyroid hormone (PTH) into the blood stream is a considerable challenge in hypoparathyroidism treatment. We recently reported that tonsil‐derived mesenchymal stem cells (TMSCs), if these cells were both differentiated in vitro before implantation and incorporated into a scaffold Matrigel, are a good cell source for parathyroid regeneration in a parathyroidectomized (PTX) animal model. Here, we present a new strategy for improved clinical application that enhances the sustained release of PTH by controlling mechanical stiffness using in situ‐forming gelatin‐hydroxyphenyl propionic acid (GH) hydrogels (GHH). Differentiated TMSCs (dTMSCs) embedded in a GHH with a strength of 4.4 kPa exhibited the best sustained release of PTH and were the most effective in hypoparathyroidism treatment, showing improved blood calcium homeostasis compared with Matrigel‐embedded dTMSCs. Interestingly, undifferentiated control TMSCs (cTMSCs) also released PTH in a sustained manner if incorporated into GHH. Collectively, these findings may establish a new paradigm for parathyroid regeneration that could ultimately evolve into an improved clinical application. Copyright © 2017 John Wiley & Sons, Ltd.     

Synthesis and characterization of poly(glycerol‐co‐sebacate‐co‐ε‐caprolactone) elastomers

In this study, poly(glycerol‐co‐sebacate‐co‐ε‐caprolactone) (PGSCL) elastomers were synthesized for the first time from the respective monomers. The structural analysis of PGSCL elastomers by nuclear magnetic resonance (¹H‐NMR) and Fourier transform infrared spectroscopy (FTIR) revealed that the elastomers have a high number of hydrogen bonds and crosslinks. X‐ray diffraction (XRD) and thermal analysis indicated an amorphous state. Differential scanning calorimetry (DSC) analysis showed that the elastomers has a glass transition temperature (T_g) of –36.96°C. The Young's modulus and compression strength values were calculated as 46.08 MPa and 3.192 MPa, respectively. Calculations based on acid number and end groups analysis revealed a number average molecular weight of 148.15 kDa. Even though the foaming studies conducted by using supercritical CO₂ resulted in a porous structure; the obtained morphology tended to disappear after 48 h, leaving small cracks on the surface. This phenomenon was interpreted as an indication of self‐healing due to the high number of hydrogen bonds. The PGSCL elastomers synthesized in this study are flexible, robust to compression forces and have self‐healing capacity. Thanks to good biocompatibility and poor cell‐adhesion properties, the elastomers may find diverse applications where a postoperative adhesion barrier is required. Copyright © 2013 John Wiley & Sons, Ltd.