Polyethylene glycol recombinant human growth hormone in Chinese prepubertal slow-growing short children: doses reported in a multicenter real-world study.

BACKGROUND: To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. METHODS: This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). RESULTS: Five hundred and ten patients were included and grouped based on dosage as A (0.10-0.14 mg/kg/week), B (0.15-0.16 mg/kg/week), C (0.17-0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was < -2 SDS or > 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P < 0.001). CONCLUSIONS: PEG-rhGH could effectively increase height in prepubertal short children. When the baseline IGF-1 was < -2 SDS, 0.10 mg/kg/week could be a starting dose. In other IGF-1 statuses, 0.15-0.20 mg/kg/week might be preferred. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03249480 , retrospectively registered.

Highly resilient porous polyurethane composite scaffolds filled with whitlockite for bone tissue engineering.

The present work is intended to provide a base for further investigation of the composite scaffolds for bone tissue engineering, and whitlockite/polyurethane (WH/PU) scaffolds, in particular. WH Ca18Mg2(HPO4)2(PO4)12 was successfully prepared by means of a chemical reaction between Ca(OH)2, Mg(OH)2 and H3PO4. WH/PU scaffolds were synthesized via in situ polymerization. Synthesized WH particles and WH/PU composite scaffolds were characterized using FTIR, XRD, SEM and EDS. The porosity of scaffolds was calculated by the liquid displacement method. The water contact angle of scaffolds was tested. Mechanical characterization of WH/PU composite scaffolds was evaluated according to monotonic and cyclic compression examination. MC3T3-E1 cells were employed to evaluate the cytocompatibility of scaffolds. The results showed that WH and PU were completely integrated into composite biomaterials. The maximum compressive strength and elastic modulus of WH/PU composite scaffold reached up to 5.2 and 14.1 MPa, respectively. WH/PU composite scaffold had maximum 73% porosity. The minimum contact angle of WH/PU composite scaffold was 89.16°. WH/PU composite scaffolds have a good elasticity. Cyclic compression tests showed that scaffold could recover 90% of its original shape 1 h after removing the load. WH/PU composite scaffolds exhibited a high affinity to MC3T3-E1 cells. WH/PU composite scaffolds significantly promoted proliferation and alkaline phosphatase activity of MC3T3-E1 cells when compared to those grown on tissue culture well plates. It is suggested that the WH/PU scaffolds might be suitable for the application of bone tissue engineering.

Abundant tannic acid modified gelatin/sodium alginate biocomposite hydrogels with high toughness, antifreezing, antioxidant and antibacterial properties.

The acidity of high tannic acid (TA) content solution can destroy the structure of protein, such as gelatin (G). This causes a big challenge to introduce abundant TA into the G-based hydrogels. Here, the G-based hydrogel system with abundant TA as hydrogen bonds provider was constructed by a "protective film" strategy. The protective film around the composite hydrogel was first formed by the chelation of sodium alginate (SA) and Ca2+. Subsequently, abundant TA and Ca2+ were successively introduced into the hydrogel system by immersing method. This strategy effectively protected the structure of the designed hydrogel. After treatment with 0.3 w/v TA and 0.06 w/v Ca2+ solutions, the tensile modulus, elongation at break and toughness of G/SA hydrogel increased about 4-, 2-, and 6-fold, respectively. Besides, G/SA-TA/Ca2+ hydrogels exhibited good water retention, anti-freezing, antioxidant, antibacterial properties and low hemolysis ratio. Cell experiments showed that G/SA-TA/Ca2+ hydrogels possessed good biocompatibility and could promote cell migration. Therefore, G/SA-TA/Ca2+ hydrogels are expected to be used in the field of biomedical engineering. The strategy proposed in this work also provides a new idea for improving the properties of other protein-based hydrogels.

Exploring the utility of Au@PVP-polyamide-Triton X-114 for SERS tracking of extracellular senescence associated-beta-galactosidase activity.

A compound with enrichment and SERS enhancement was successfully developed, which could rapidly adsorb X-gal hydrolysates from a liquid matrix in 5 minutes and further be used for SERS analysis with a detection limit of less than 1 × 10-9 mol L-1. This novel strategy will facilitate the development of an analytical approach for cellular senescence.

Alginate microgels as delivery vehicles for cell-based therapies in tissue engineering and regenerative medicine.

Conventional stem cell delivery typically utilize administration of directly injection of allogenic cells or domesticated autogenic cells. It may lead to immune clearance of these cells by the host immune systems. Alginate microgels have been demonstrated to improve the survival of encapsulated cells and overcome rapid immune clearance after transplantation. Moreover, alginate microgels can serve as three-dimensional extracellular matrix to support cell growth and protect allogenic cells from rapid immune clearance, with functions as delivery vehicles to achieve sustained release of therapeutic proteins and growth factors from the encapsulated cells. Besides, cell-loaded alginate microgels can potentially be applied in regenerative medicine by serving as injectable engineered scaffolds to support tissue regrowth. In this review, the properties of alginate and different methods to produce alginate microgels are introduced firstly. Then, we focus on diverse applications of alginate microgels for cell delivery in tissue engineering and regenerative medicine.

Coated electrospun polyamide-6/chitosan scaffold with hydroxyapatite for bone tissue engineering.

Polyamide-6 (PA6) is a synthetic polymer that bears resemblance to collagen in its backbone and has excellent stability in human body fluid. Chitosan (CS) with the similar structure to that of the polysaccharides existing in the extracellular matrix (ECM), has a more suitable biodegradation rate for the formation of new-bone. Electrospun fiber have nanoscale structure, high porosity and large specific surface area, can simulate the structure and biological function of the natural ECM. To meet the requirements of mechanical properties and biocompatibility of bone tissue engineering, electrospun PA6/CS scaffolds were fabricated by electrospinning technology. The mineralized PA6/CS scaffolds were obtained through immersion in 1.5× simulated body fluid (1.5SBF), which allowed the hydroxyapatite (HA) layer to grow into the thickness range under very mild reaction conditions without the need of a prior chemical modification of the substrate surface. The results showed that electrospun PA6/CS fibrous scaffolds in the diameter range of 60-260 nm mimic the nanostructure of the ECM. The tensile strength and modulus of 10PA6/CS fibrous scaffolds reach up to 12.67 ± 2.31 MPa and 95.52 ± 6.78 MPa, respectively. After mineralization, HA particles uniformly distributed on the surface of PA6/CS fibrous scaffolds in a porous honeycomb structure, and the content of mineral was about 40%. In addition, cell culture study indicated that the mineralized PA6/CS composite scaffolds were non-cytotoxic, and had a good biocompatibility and an ability to promote MC3T3-E1 cell attachment and proliferation.

Electrospun polyamide-6/chitosan nanofibers reinforced nano-hydroxyapatite/polyamide-6 composite bilayered membranes for guided bone regeneration.

Periodontal defect poses a significant challenge in orthopedics. Guided Bone Regeneration (GBR) membrane is considered as one of the most successful methods applied to reconstruct alveolar bone and then to achieve periodontal defect repair/regeneration. In this paper, a novel polyamide-6/chitosan@nano-hydroxyapatite/polyamide-6 (PA6/CS@n-HA/PA6) bilayered tissue guided membranes by combining a solvent casting and an electrospinning technique was designed. The developed PA6/CS@n-HA/PA6 composites were characterized by a series of tests. The results show that n-HA/PA6 and electrospun PA6/CS layers are tightly bound by molecular interaction and chemical bonding, which enhances the bonding strength between two distinct layers. The porosity and adsorption average pore diameter of the PA6/CS@n-HA/PA6 membranes are 36.90 % and 22.61 nm, respectively. The tensile strength and elastic modulus of PA6/CS@n-HA/PA6 composites are 1.41 ± 0.18 MPa and 7.15 ± 1.09 MPa, respectively. In vitro cell culture studies demonstrate that PA6/CS@n-HA/PA6 bilayered scaffolds have biological safety, good bioactivity, biocompatibility and osteoconductivity.

Porous PVA/SA/HA hydrogels fabricated by dual-crosslinking method for bone tissue engineering.

In the present work, a new kind of porous polyvinyl alcohol/sodium alginate/hydroxyapatite (PVA/SA/HA) composite hydrogels with tunable structure and mechanical properties have been fabricated by dual-crosslinking method. The morphologies, moisture content, porosity and mechanical properties of the composite hydrogels have been investigated in detail. The PVA/SA/HA hydrogels present uniform, interpenetrating porous structure. The FTIR and XRD results indicate that PVA, SA and HA could be uniformly compounded. The mechanical properties, moisture content and porosity of the samples could be controlled by changing the mass ratio of PVA/SA/HA. The optimized compression modulus (41.74 ± 7.86 kPa), moisture content (86.99 ± 0.72%) and porosity (79.98 ± 1.61%) of the composite hydrogels could be achieved via fixing the weight ratio of PVA/SA/HA at 42:18:40. In vitro biodegradation and mineralization of the composite hydrogels show that the hydrogels could gradually be degraded in PBS solution and sheet-like HA nanocrystals are easily formed on the surface. Moreover, cell culture results indicate that the PVA/SA/HA hydrogels have no negative effects on MC3T3-E1 cell growth and proliferation. Alkaline phosphatase (ALP) activity expressions demonstrate that the nano-HA crystals incorporated composite hydrogels obviously improve the ALP activity of the cells. It confirms that the prepared PVA/SA/HA hydrogels could be a promising candidate for bone repair and bone tissue engineering.

High strength polyvinyl alcohol/polyacrylic acid (PVA/PAA) hydrogel fabricated by Cold-Drawn method for cartilage tissue substitutes.

Poly (vinyl alcohol) (PVA) hydrogel has been considered as promising cartilage replacement materials due to its excellent characteristics such as high water content, low frictional behavior and excellent biocompatibility. However, lack of sufficient mechanical properties and cytocompatibility are two key obstacles for PVA hydrogel to be applied as cartilage substitutes. Herein, Polyacrylic acid (PAA) has been introduced into PVA hydrogel to balance these problems. Compared with pure PVA hydrogel, PVA/PAA hydrogel has the equal excellent biocompatibility, and its cell adhesion is significantly improved. In order to further improve the mechanical properties of hydrogels, Cold-Drawn treatment of hydrogels is performed in this paper. Compared to pure 12% PVA hydrogel, 40.8-fold, 50.8-fold, and 46.8-fold increase in tensile strength, tensile modulus, and toughness, respectively, which can be obtained from 12% PVA/PAA Cold-Drawn hydrogel. These biocompatible composite hydrogels have a great application potential as cartilage tissue substitutes.