RESUMEN
The innate cartilage extracellular matrix is avascular and plays a vital role in innate chondrocytes. Recapping the crucial components of the extracellular matrix in engineered organs via polymeric gels and bioinspired approaches is promising for improving the regenerative aptitude of encapsulated cartilage/chondrocytes. Conventional gel formation techniques for polymeric materials rely on employing oxidative crosslinking, which is constrained in this avascular environment. Further, poor mechanical properties limit the practical applications of polymeric gels and reduce their therapeutic efficacy. Herein, the purpose of this study was to develop a bioadhesive gel possessing dual crosslinking for engineering cartilage. Tyramine (TYR) was first chemically conjugated to the alginate (ALG) backbone to form an ALG-TYR precursor, followed by the addition of calcium peroxide (CaO2); calcium ions of CaO2 physically crosslink with ALG, and oxygen atoms of CaO2 chemically crosslink TYR with tyrosinase, thus enabling dual/enhanced crosslinking and possessing injectability. The ALG-TYR/tyrosinase/CaO2 gel system was chemically, mechanically, cellularly, and microscopically characterized. The gel system developed herein was biocompatible and showed augmented mechanical strength. The results showed, for the first time, that CaO2 supplementation preserved cell viability and enhanced the crosslinking ability, bioadhesion, mechanical strength, chondrogenesis, and stability for cartilage regeneration.
Asunto(s)
Alginatos , Monofenol Monooxigenasa , Alginatos/química , Cartílago , Condrocitos , Condrogénesis , Hidrogeles/química , Peróxidos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , TiraminaRESUMEN
The skin possesses an epithelial barrier. Delivering growth factors to deeper wounds is usually rather challenging, and these typically restrict the therapeutic efficacy for chronic wound healing. Efficient healing of chronic wounds also requires abundant blood flow. Therefore, addressing these concerns is crucial. Among presently accessible biomedical materials, tailored hydrogels are favorable for translational medicine. However, these hydrogels display insufficient mechanical properties, hampering their biomedical uses. Cold-atmospheric plasma (CAP) has potent cross-linking/polymerizing abilities. The CAP was characterized spectroscopically to identify excited radiation and species (hydroxyl and UV). CAP was used to polymerize pyrrole (creating Ppy) and crosslink hybrid polymers (Ppy, hyaluronic acid (HA), and gelatin (GEL)) as a multimodal dressing for chronic wounds (CAP-Ppy/GEL/HA), which were used to incorporate therapeutic platelet proteins (PPs). Herein, the physicochemical and biological features of the developed CAP-Ppy/GEL/HA/PP complex were assessed. CAP-Ppy/GEL/HA/PPs had positive impacts on wound healing in vitro. In addition, the CAP-Ppy/GEL/HA complex has improved mechanical aspects, therapeutics sustained-release/retention effect, and near-infrared (NIR)-driven photothermal-hyperthermic effects on lesions that drive the expression of heat-shock protein (HSP) with anti-inflammatory properties for boosted restoration of diabetic wounds in vivo. These in vitro and in vivo outcomes support the use of CAP-Ppy/GEL/HA/PPs for diabetic wound regeneration.
Asunto(s)
Gases em Plasma , Polímeros , Regeneración , Ciencia Traslacional Biomédica , Cicatrización de HeridasRESUMEN
Patients with irregular, huge burn wounds require time-consuming healing. The skin has an epithelial barrier mechanism. Hence, the penetration and retention of therapeutics across the skin to deep lesion is generally quite difficult and these usually constrain the delivery/therapeutic efficacies for wound healing. Effective burn wound healing also necessitates proper circulation. Conventional polymeric dressing usually exhibits weak mechanical behaviors, obstructing their load-bearing applications. Cold atmospheric plasma (CAP) was used as an efficient, environmentally friendly, and biocompatible process to crosslink methylcellulose (MC) designed for topical administration such as therapeutic substances of platelets (SP) and polyethyleneimine-polypyrrole nanoparticle (PEI-PPy NP)-laden MC hydrogel carriers, and wound dressings. The roles of framework parameters for CAP-treated SP-PEI-PPy NP-MC polymeric complex system; chemical, physical, and photothermal effects; morphological, spectroscopical, mechanical, rheological, and surface properties; in vitro drug release; and hydrophobicity are discussed. Furthermore, CAP-treated SP-PEI-PPy NP-MC polymeric complex possessed augmented mechanical properties, biocompatibility, sustainable drug release, drug-retention effects, and near-infrared (NIR)-induced hyperthermia effects that drove heat-shock protein (HSP) expression with drug permeation to deep lesions. This work sheds light on the CAP crosslinking polymeric technology and the efficacy of combining sustained drug release with photothermal therapy in burn wound bioengineering carrier designs.
Asunto(s)
Plaquetas/efectos de los fármacos , Quemaduras/terapia , Metilcelulosa/química , Metilcelulosa/efectos de la radiación , Gases em Plasma/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Fenómenos Químicos , Humanos , Ratones , Ratas , Análisis EspectralRESUMEN
Several studies have applied tricalcium phosphate (TCP) or autografts in bone tissue engineering to enhance the clinical regeneration of bone. Unfortunately, there are several drawbacks related to the use of autografts, including a risk of infection, blood loss, limited quantities, and donor-site morbidities. Platelet-rich fibrin (PRF) is a natural extracellular matrix (ECM) biomaterial that possesses bioactive factors, which can generally be used in regenerative medicine. The goal of the present investigation was to develop osteoconductive TCP incorporated with bioactive PRF for bio-synergistic bone regeneration and examine the potential biological mechanisms and applications. Our in vitro results showed that PRF plus TCP had excellent biosafety and was favorable for initiating osteoblast cell attachment, slow release of bioactive factors, cell proliferation, cell migration, and ECM formation that potentially impacted bone repair. In a rabbit femoral segmental bone defect model, regeneration of bone was considerably augmented in defects locally implanted by PRF plus TCP according to radiographic and histologic examinations. Notably, the outcomes of this investigation suggest that the combination of PRF and TCP possesses novel synergistic and bio-inspired functions that facilitate bone regeneration.