OBJECTIVE: To summarize the biomechanical research progress of biomaterials in rotator cuff injury repair and to explore how biomaterials can restore the native histological and mechanical properties of the rotator cuff. METHODS: The relevant literature at home and abroad was widely reviewed to analyze the biomechanical properties of synthetic biomaterials, naturally derived biomaterials, and tissue grafts in the repair of rotator cuff injuries. RESULTS: Synthetic biomaterials [such as poly (lactic-co-glycolic acid) and polycaprolactone] can provide initial stable mechanical support due to their adjustable mechanical properties and degradation characteristics, while naturally derived biomaterials (such as collagen and hyaluronic acid) can promote cell adhesion and tissue integration due to their biocompatibility and bioactivity. Tissue grafts exhibit significant clinical utility by providing immediate mechanical stability and promoting tendon-to-bone healing. Three-dimensional bioprinting technology provides new possibilities for personalized repair of rotator cuff injuries by precisely controlling the spatial distribution and mechanical properties of biomaterials. CONCLUSION Future studies should further optimize the design of bioprinting materials, cell sources, and scaffolds to achieve better mechanical properties and clinical efficacy of biomaterials in the repair of rotator cuff injuries.
Humans ; Rotator Cuff Injuries ; Biocompatible Materials/chemistry* ; Biomechanical Phenomena ; Tissue Scaffolds ; Rotator Cuff/surgery* ; Tissue Engineering/methods* ; Polyesters ; Polyglycolic Acid/chemistry* ; Hyaluronic Acid/chemistry* ; Collagen/chemistry* ; Lactic Acid/chemistry* ; Polylactic Acid-Polyglycolic Acid Copolymer ; Bioprinting ; Wound Healing ; Printing, Three-Dimensional ; Tendon Injuries/surgery*

OBJECTIVES: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality. METHODS: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay. RESULTS: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities. CONCLUSIONS The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Microspheres ; Hyaluronic Acid/chemistry* ; Humans

BACKGROUND: Lung cancer currently ranks first globally in both incidence and mortality. Pemetrexed (PMX) serves as a first-line treatment for lung adenocarcinoma (LUAD), but the patients often develop drug resistance during therapy. Milk exosome (mEXO) have the advantages of low immunogenicity, high tissue affinity, and low cost, and mEXO itself has anti-tumor effects. Hyaluronan (HA) naturally bind to CD44, a receptor which is highly expressed in LUAD tissues. This study aims to construct hyaluronan-modified milk exosome (HA-mEXO) and preliminarily investigate their molecular mechanisms for reversing PMX resistance through cellular experiments. METHODS: Exosomes were extracted from milk using high-speed centrifugation, and HA-mEXO was constructed. PMX-resistant A549 and PC-9 cell lines were treated with mEXO and HA-mEXO, respectively. CCK-8 assays, colony formation assays, Transwell assays, and flow cytometry were performed to evaluate proliferation, colony formation, migration, invasion, and apoptosis phenotypes in the treated resistant cell lines. Finally, transcriptomic sequencing, analysis, and cellular functional recovery experiments were conducted to investigate the mechanism by which HA-mEXO reverses PMX resistance in LUAD cells. RESULTS: The expression of CD44 in A549 and PC-9 LUAD drug-resistant cell lines was significantly higher than that in parental cells, and the uptake rate of HA-mEXO by drug-resistant cell lines was significantly higher than that of mEXO. Compared to the mEXO group, HA-mEXO-treated A549 and PC-9 resistant cells exhibited significantly reduced half maximal inhibitory concentration (IC50) values for PMX, markedly diminished clonogenic, migratory, and invasive capabilities, and a significantly increased proportion of apoptotic cells. Western blot analysis revealed that, compared to parental cells, A549 and PC-9 drug-resistant cells exhibited downregulated ZNF516 expression and upregulated ABCC5 expression. Immunofluorescence analysis revealed that HA-mEXO treatment downregulated ABCC5 expression in A549 and PC-9 drug-resistant cells compared to the PBS group, whereas co-treatment with HA-mEXO and ZNF516 knockdown showed no significant change in ABCC5 expression. CONCLUSIONS HA-mEXO carrying ZNF516 suppress ABCC5 expression, thereby enhancing the sensitivity of A549 and PC-9 LAUD drug-resistant cells to PMX.
Humans ; Hyaluronic Acid/chemistry* ; Drug Resistance, Neoplasm/drug effects* ; Exosomes/chemistry* ; Adenocarcinoma of Lung/genetics* ; Pemetrexed/pharmacology* ; Animals ; Lung Neoplasms/pathology* ; Milk/chemistry* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Hyaluronan Receptors/metabolism*

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

The development of safe and effective carriers is crucial for improving the in vivo stability of siRNA drugs and facilitating their clinical translation. Chitosan (CS), a natural cationic polymer, shows great potential in nucleic acid drug delivery. To optimize the physicochemical properties of CS/siRNA nanoparticles (NPs) and increase their siRNA delivery efficacy, in this study, hyaluronic acid (HA) was added into CS to form stable complex NPs through electrostatic interactions. The HA component is able to target the CD44 receptors on the surface of tumor cells, facilitating efficient siRNA delivery. First, we systematically investigated the effects of the molecular weights and mass ratio of CS and HA on the physicochemical properties of CS/HA NPs. The results showed that at HA: CS mass ratios of approximately 5:5 and 6:4, the complex NPs exhibited small particle sizes, narrow size distribution, and high storage stability. Under similar conditions, the size of CS/HA NPs increased with the increase in the molecular weights of CS and HA. Based on these findings, suitable conditions were selected to prepare CS/HA NPs for siRNA delivery. Cell experiments demonstrated that the introduction of HA effectively reduced the cytotoxicity of the CS delivery system and enhanced the NP uptake. The CS/HA/siRNA NPs achieved 50% to 60% silencing of the luciferase gene in HeLa-Luc cells. CS/HA NPs formed smaller nanoparticles with siRNA than pure CS and mediated specific interactions with tumor cells via HA, leading to efficient siRNA delivery. These findings provide valuable insights into the construction of natural polymer composite nanoparticles for application in siRNA delivery.
Hyaluronic Acid/chemistry* ; Chitosan/chemistry* ; RNA, Small Interfering/administration & dosage* ; Nanoparticles/chemistry* ; Humans ; Particle Size ; HeLa Cells ; Hyaluronan Receptors

Collagen contains abundant cell binding motifs, which are conducive to adhesion, migration, and differentiation, maintain cell vitality and promote cell proliferation. However, pure collagen hydrogel has some shortcomings such as poor mechanical properties, poor thermal stability and fast degradation. Numerous studies have shown that the properties of collagen can be improved by combining it with natural polysaccharides such as alginate, chitosan, hyaluronic acid and cellulose. In this paper, the research status and biological application fields of four kinds of composite hydrogels, including collagen-alginate composite hydrogels, collagen-chitosan hydrogels, collagen-hyaluronic acid hydrogels and collagen-cellulose hydrogels, were summarized. The common preparation methods of four kinds of composite hydrogels were introduced, and the future development direction of collagen-based composite hydrogels was prospected.
Hydrogels/chemical synthesis* ; Collagen/chemistry* ; Polysaccharides/chemistry* ; Alginates/chemistry* ; Hyaluronic Acid/chemistry* ; Chitosan/chemistry* ; Biocompatible Materials/chemistry* ; Humans ; Tissue Engineering/methods* ; Cellulose/chemistry* ; Tissue Scaffolds

OBJECTIVES: To design and prepare silk fibroin/hyaluronic acid composite hydrogel. METHODS: The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by ¹H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope. RESULTS: The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good. CONCLUSIONS The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Hyaluronic Acid/chemistry* ; Biocompatible Materials/chemistry* ; Click Chemistry ; Sulfhydryl Compounds ; Silk/chemistry*

Soft tissue is an indispensable tissue in human body. It plays an important role in protecting the body from external physical, chemical or biological factors. Mild soft tissue injuries can self-heal, while severe soft tissue injuries may require related treatment. Natural polymers (such as chitosan, hyaluronic acid, and collagen) and synthetic polymers (such as polyethylene glycol and polylactic acid) exhibit good biocompatibility, biodegradability and low toxicity. It can be used for soft tissue repairs for antibacterial, hemostatic and wound healing purposes. Their related properties can be enhanced through modification or preparation of composite materials. Commonly used soft tissue repairs include wound dressings, biological patches, medical tissue adhesives, and tissue engineering scaffolds. This study introduces the properties, mechanisms of action and applications of various soft tissue repair medical materials, including chitosan, hyaluronic acid, collagen, polyethylene glycol and polylactic acid, and provides an outlook on the application prospects of soft tissue repair medical materials and products.
Humans ; Biocompatible Materials/chemistry* ; Chitosan/chemistry* ; Hyaluronic Acid ; Tissue Scaffolds/chemistry* ; Collagen/chemistry* ; Polymers/chemistry* ; Polyethylene Glycols ; Soft Tissue Injuries

In this study, insulin (insulin, INS)/Ca₃PO₄ complex and glucose oxidase (glucose oxidase, GOx)/Cu₃(PO₄)₂ complex were prepared by coprecipitation method. The mineralized insulin (mineralized insulin, m-INS) showed irregular crystalline clusters, and the mineralized glucose oxidase (m-GOx) showed flower spherical morphology, with a diameter of about 1-2 μm. In vitro simulated release experiment showed that m-INS released INS as the pH value of the medium decreased. When the pH value was 4.5, the release amount reached 96.68%. The enzyme activity detection experiment showed that the enzyme activity stability of m-GOx was higher than that of free GOx. It still maintained high activity after 10 days at room temperature, while the activity of GOx was less than 60%. The glucose solution was prepared to simulate the state of normal blood glucose (5.6 mmol/L) and hyperglycemia (22.2 mmol/L). When m-INS and m-GOx were added to the glucose solution, the release amount of INS showed a significant glucose concentration dependence. The higher the glucose concentration, the greater the release amount and release rate of INS. Finally, m-INS, m-GOx and hyaluronic acid (HA) solution were mixed to prepare HA microneedle arrays loaded with m-INS and m-GOx. Type 1 diabetes mice were constructed to evaluate the effect of drug-loaded HA microarray on blood glucose control in diabetic rats. The results show that the HA microneedles loaded with m-INS/m-GOx could deliver drugs effectively. The average blood glucose concentration in diabetic rats dropped to about 7 mmol/L within 1 h, normal blood glucose concentration could be maintained for 10 h, and the overall blood glucose concentration was lower than the level before administration for 36 hours. Compared with HA microneedles loaded with INS only, m-ins microneedles showed better glucose tolerance, longer-lasting glucose control effect and less risk of hypoglycemia. Compared with other sustained-release systems, the preparation process of the core components in this study is simple, efficient, safe and effective, and has great commercial potential.
Animals ; Blood Glucose ; Delayed-Action Preparations/therapeutic use* ; Diabetes Mellitus, Experimental/drug therapy* ; Drug Delivery Systems/methods* ; Glucose Oxidase/chemistry* ; Hyaluronic Acid ; I Blood-Group System ; Insulin/therapeutic use* ; Mice ; P Blood-Group System ; Rats

According to literature, certain microorganism productions mediate biological effects. However, their beneficial characteristics remain unclear. Nowadays, scientists concentrate on obtaining natural materials from live creatures as new sources to produce innovative smart biomaterials for increasing tissue reconstruction in tissue engineering and regenerative medicine. The present review aims to introduce microorganism-derived biological macromolecules, such as pullulan, alginate, dextran, curdlan, and hyaluronic acid, and their available sources for tissue engineering. Growing evidence indicates that these materials can be used as biological material in scaffolds to enhance regeneration in damaged tissues and contribute to cosmetic and dermatological applications. These natural-based materials are attractive in pharmaceutical, regenerative medicine, and biomedical applications. This study provides a detailed overview of natural-based biomaterials, their chemical and physical properties, and new directions for future research and therapeutic applications.
Biocompatible Materials/chemistry* ; Humans ; Hyaluronic Acid ; Regenerative Medicine ; Tissue Engineering ; Tissue Scaffolds/chemistry*