OBJECTIVES: To synthesize a temperature-responsive multimodal motion microrobot (MMMR) using temperature and magnetic field-assisted microfluidic droplet technology to achieve targeted drug delivery and controlled drug release. METHODS: Microfluidic droplet technology was utilized to synthesize the MMMR by mixing gelatin with magnetic microparticles. The microrobot possessed a magnetic anisotropy structure to allow its navigation and targeted drug release by controlling the temperature field and magnetic field. In the experiment, the MMMR was controlled to move in a wide range along a preset path by rotating a uniform magnetic field, and the local circular motion was driven by a planar rotating gradient magnetic field of different frequencies. The MMMR was loaded with simulated drugs, which were released in response to laser heating. RESULTS: Driven by a rotating magnetic field, the MMMR achieved linear motion following a predefined path. The planar gradient rotating magnetic field controlled circular motion of the MMMR with an adjustable radius, utilizing the centrifugal force generated by rotation. The drug-loaded MMMR successfully reached the target location under magnetic guidance, where the gelatin matrix was melted using laser heating for accurate drug release, after which the remaining magnetic particles were removed using magnetic field. CONCLUSIONS The MMMR possesses multimodal motion capabilities to enable precise navigation along a predefined path and dynamic regulation of drug release within the target area, thus having great potential for a wide range of biomedical applications.
Drug Delivery Systems/methods* ; Temperature ; Drug Liberation ; Magnetic Fields ; Robotics ; Gelatin/chemistry* ; Delayed-Action Preparations ; Microfluidics ; Motion

Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured

Gelatin microspheres were discussed as a scaffold material for bone tissue engineering, with the advantages of its porosity, biodegradability, biocompatibility, and biosafety highlighted. This review discusses how bone regeneration is aided by the three fundamental components of bone tissue engineering-seed cells, bioactive substances, and scaffold materials-and how gelatin microspheres can be employed for in vitro seed cell cultivation to ensure efficient expansion. This review also points out that gelatin microspheres are advantageous as drug delivery systems because of their multifunctional nature, which slows drug release and improves overall effectiveness. Although gelatin microspheres are useful for bone tissue creation, the scaffolds that take into account their porous structure and mechanical characteristics might be difficult to be created. This review then discusses typical techniques for creating gelatin microspheres, their recent application in bone tissue engineering, as well as possible future research directions.
Tissue Engineering/methods* ; Tissue Scaffolds/chemistry* ; Gelatin/chemistry* ; Microspheres ; Bone and Bones ; Porosity

Wound repair is a common clinical problem, which seriously affects the quality of life of patients and also brings a heavy burden to the society. Hydrogel-based multifunctional dressing has shown strong potential in the treatment of acute and chronic wounds. In addition to its good histocompatibility, cell adhesion, and biodegradability, methacrylic anhydride gelatin (GelMA) hydrogel has also attracted much attention due to its low cost, mild reaction conditions, adjustable physicochemical properties, and wide clinical applications. In this paper, the characteristics of GelMA hydrogel and its research progress in wound repair are introduced, and the future development of multifunctional GelMA hydrogel dressing for wound treatment is prospected.
Humans ; Gelatin/chemistry* ; Hydrogels ; Anhydrides ; Quality of Life ; Methacrylates/chemistry*

Cervi Colla, deer's gelatin, had two kinds of original sources historically, including the skin and antler of deer, known as Cervi Corii Colla(Lupijiao, LPJ) and Cervi Cornus Colla(Lujiaojiao, LJJ) respectively.LJJ is the mainstream of the market, while LPJ is only used by common people in Guizhou and Jilin etc. This article sorted out the ancient and modern literature(since Rites of the Zhou in Zhou Dynasty) on Cervi Colla and conducted the herbalogical study. The results of the study include:① In ancient China, there were six types of commonly-used Colla derived from six animals, including deer, horse, cow, rat, fish and rhinoceros. Cervi Colla was ranked the most top among them, and it was often used as adhesive to make bow and Chinese inksticks and more commonly used as a medicine.Cervi Cornus Colla was first described as a medicinal by the name "Bai Jiao"(white gelatin)in The Divine Husbandman's Classic of Material Medica(Shen Nong Ben Cao Jing).② Initially, both the skin and antler were used as raw materials to make Cervi Colla, but antler became the only raw material, and deer skin disappeared from the mainstream of raw materials for Cervi Colla. This can be attributed to other diverse and luxurious uses of the skin, such as making dress and hats, etc., and the easy accessibility of deer antlers. ③ The sources of Cervi Colla were not limited to Cervus elaphus(red deer) or C. nippon(sika deer), and it also included animal from the family Cervidae, such as Elaphurus davidianus(elk) and C. unicolor(sambar). ④ The processing method was passed down from ancient times to the present, and no significant changes had occurred. ⑤ LPJ and LJJ had many similar effects, and their nature was both warm. The effect of LJJ was to warm the liver and kidney, replenish vital essence and blood, and to reinforce Yang. While the effect of LPJ was to reinforce both Yin and Yang, replenish blood, and stop bleeding. It has a unique advantage for both reinforcing Yin and Yang. The findings of this paper can provide support for the promotion of LPJ and the development of its medicinal value.
Animals ; Antlers/chemistry* ; China ; Deer ; Gelatin/chemistry* ; Materia Medica/chemistry* ; Skin/chemistry*

Novel hydrogel composed of both chondroitin sulfate (CS) and gelatin was developed for better cellular interaction through two step double crosslinking of N-(3-diethylpropyl)-N-ethylcarbodiimide hydrochloride (EDC) chemistries and then click chemistry. EDC chemistry was proceeded during grafting of amino acid dihydrazide (ADH) to carboxylic groups in CS and gelatin network in separate reactions, thus obtaining CS–ADH and gelatin–ADH, respectively. CS–acrylate and gelatin–TCEP was obtained through a second EDC chemistry of the unreacted free amines of CS–ADH and gelatin–ADH with acrylic acid and tri(carboxyethyl)phosphine (TCEP), respectively. In situ CS–gelatin hydrogel was obtained via click chemistry by simple mixing of aqueous solutions of both CS–acrylate and gelatin–TCEP. ATR-FTIR spectroscopy showed formation of the new chemical bonds between CS and gelatin in CS–gelatin hydrogel network. SEM demonstrated microporous structure of the hydrogel. Within serial precursor concentrations of the CS–gelatin hydrogels studied, they showed trends of the reaction rates of gelation, where the higher concentration, the quicker the gelation occurred. In vitro studies, including assessment of cell viability (live and dead assay), cytotoxicity, biocompatibility via direct contacts of the hydrogels with cells, as well as measurement of inflammatory responses, showed their excellent biocompatibility. Eventually, the test results verified a promising potency for further application of CS–gelatin hydrogel in many biomedical fields, including drug delivery and tissue engineering by mimicking extracellular matrix components of tissues such as collagen and CS in cartilage.
Amines ; Cartilage ; Cell Survival ; Chemistry ; Chondroitin Sulfates ; Chondroitin ; Click Chemistry ; Collagen ; Extracellular Matrix ; Gelatin ; Hydrogel ; Hydrogels ; In Vitro Techniques ; Spectrum Analysis ; Tissue Engineering ; Transplants

BACKGROUNDThree-dimensional (3D) printing technology holds great promise for treating diseases or injuries that affect human bones with enhanced performance over traditional techniques. Different patterns of design can lead to various mechanical properties and biocompatibility to various degrees. However, there is still a long way to go before we can fully take advantage of 3D printing technologies.

METHODSThis study tailored 3D printed scaffolds with gelatin and platelets to maximize bone regeneration. The scaffolds were designed with special internal porous structures that can allow bone tissue and large molecules to infiltrate better into the scaffolds. They were then treated with gelatin and platelets via thermo-crosslinking and freeze-drying, respectively. Vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-β1 were measured at different time points after the scaffolds had been made. Cell proliferation and cytotoxicity were determined via cell counting kit-8 (CCK-8) assay.

RESULTSThere was a massive boost in the level of VEGF and TGF-β1 released by the scaffolds with gelatin and platelets compared to that of scaffolds with only gelatin. After 21 days of culture, the CCK-8 cell counts of the control group and treated group were significantly higher than that of the blank group (P < 0.05). The cytotoxicity test also indicated the safety of the scaffolds.

CONCLUSIONSOur experiments confirmed that the 3D printed scaffolds we had designed could provide a sustained-release effect for growth factors and improve the proliferation of preosteoblasts with little cytotoxicity in vitro. They may hold promise as bone graft substitute materials in the future.

3T3 Cells ; Animals ; Biocompatible Materials ; chemistry ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Gelatin ; chemistry ; Mice ; Printing, Three-Dimensional ; Tissue Engineering ; methods ; Tissue Scaffolds ; chemistry ; Transforming Growth Factor beta1 ; chemistry ; pharmacology ; Vascular Endothelial Growth Factor A ; chemistry ; pharmacology

OBJECTIVE: To evaluate the feasibility, safety, and clinical outcomes of plug-assisted retrograde transvenous obliteration (PARTO) to treat gastric variceal hemorrhage in patients with portal hypertension. MATERIALS AND METHODS: From May 2012 to June 2014, 19 patients (11 men and 8 women, median age; 61, with history of gastric variceal hemorrhage; 17, active bleeding; 2) who underwent PARTO using a vascular plug and a gelfoam pledget were retrospectively analyzed. Clinical and laboratory data were examined to evaluate primary (technical and clinical success, complications) and secondary (worsening of esophageal varix [EV], change in liver function) end points. Median follow-up duration was 11 months, from 6.5 to 18 months. The Wilcoxon signed-rank test was used to compare laboratory data before and after the procedure. RESULTS: Technical success (complete occlusion of the efferent shunt and complete filling of gastric varix [GV] with a gelfoam slurry) was achieved in 18 of 19 (94.7%) patients. The embolic materials could not reach the GV in 1 patient who had endoscopic glue injection before our procedure. The clinical success rate (no recurrence of gastric variceal bleeding) was the same because the technically failed patient showed recurrent bleeding later. Acute complications included fever (n = 2), fever and hypotension (n = 2; one diagnosed adrenal insufficiency), and transient microscopic hematuria (n = 3). Ten patients underwent follow-up endoscopy; all exhibited GV improvement, except 2 without endoscopic change. Five patients exhibited aggravated EV, and 2 of them had a bleeding event. Laboratory findings were significantly improved after PARTO. CONCLUSION: PARTO is technically feasible, safe, and effective for gastric variceal hemorrhage in patients with portal hypertension.
Aged ; Balloon Occlusion ; Embolization, Therapeutic ; Endoscopy, Digestive System ; Esophageal and Gastric Varices/complications/radiography/*therapy ; Female ; Gastrointestinal Hemorrhage/therapy ; Gelatin Sponge, Absorbable/chemistry ; Humans ; Hypertension, Portal/complications ; Male ; Middle Aged ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVETo investigate the influence of gelatin particle (GP) size and gelatin/calcium phosphate cement (GP/CPC) ratio on repairing potency of comparison artificial bone material.

METHODSComposite GP/CPC materials with different GP size (100~200 μm vs. 200~300 μm) and ratio(5% vs. 10%) were prepared. Physiochemical and biological properties, including porosity, resistance to compression, ultrastructure and biocompatibility were compared among 4 groups of GP/CPC materials. Different GP/CPC materials were used to repair the critical-size cranial bone defect in rabbit model, and the histology and newly formed bone inside scaffolds (nBIS) were examined and compared among different groups.

RESULTSGP/CPC with GP of 200~300 μm possessed larger micropores than that with GP of 100~200 μm (P<0.05). The GP/CPC containing 10% GP had higher porosity than that containing 5% GP (P<0.05). The animal model study showed that more new bone formed in those defects filled with GP/CPC containing 10% GP with 200~300 μm in size compared with GP/CPC containing 5% GP with 100~200 μm in size (P<0.05). While GP/CPC containing 5% GP with 100~200 μm in size showed a higher level of resistance to compression.

CONCLUSIONBoth the particle size of GP and its ratio in the GP/CPC affect the properties of the composite biomaterials and their role in bone repairing. In particular, the GP/CPC containing 10% GP with 200~300 μm in size is most suitable for repairing critical-size cranial bone defect in animal model.

Animals ; Biocompatible Materials ; chemistry ; Bone Cements ; chemistry ; Calcium Phosphates ; chemistry ; Gelatin ; chemistry ; Osteogenesis ; Particle Size ; Porosity ; Rabbits ; Tissue Scaffolds

OBJECTIVE: Arterial stenosis is a major obstacle for subsequent interventional procedures. We hypothesized that the stenosis is caused by gelatin sponge embolization and performed an experimental study in a rabbit renal model. MATERIALS AND METHODS: A total of 24 rabbits were embolized with porcine gelatin sponge particles injected into the renal arteries. Four rabbits were sacrificed on 1 day, 4 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after embolization. Microscopic evaluations were performed on hematoxylin-eosin and smooth muscle actin immunohistochemical stained sections. RESULTS: Gelatin sponge particles were mainly observed in the segmental and interlobar arteries. Transmural inflammation of the embolized arterial wall and mild thickening of the media were observed 1 week after embolization. Resorption of the gelatin sponge and organization of thrombus accompanied by foreign body reactions, were observed from 2 to 4 weeks after embolization. Microscopic images of the 3 weeks group showed vessel lumens filled mostly with organized thrombi, resulting in severe stenosis. Additionally, vessels showed a thickened intima that contained migrating smooth muscle cells and accompanying interruption of the internal elastic lamina. The migrating smooth muscle cells were distributed around the recanalized arterial lumen. CONCLUSION: Gelatin sponge embolization may induce arterial stenosis by causing organized thrombus and intimal hyperplasia, which consists of migrating smooth muscle cells and intimal collagen deposits.
Animals ; Constriction, Pathologic/*etiology ; Disease Models, Animal ; Embolization, Therapeutic/*adverse effects ; Gelatin ; Gelatin Sponge, Absorbable/*chemistry ; Kidney/*blood supply ; Male ; Porifera ; Rabbits ; Renal Artery/*pathology/radiography ; Swine