Optimizing an Injectable Composite Oxygen-Generating System for Relieving Tissue Hypoxia

Abstract

Oxygen deficiency resulting from bone fracture-induced vascular disruption leads to massive cell death and delayed osteoblast differentiation, ultimately impairing new bone formation and fracture healing. Enhancing local tissue oxygenation can help promote bone regeneration. In this work, an injectable composite oxygen-generating system consisting of calcium peroxide (CaO 2 )/manganese dioxide (MnO 2 )-encapsulated poly lactic-co-glycolic acid (PLGA) microparticles (CaO 2 + MnO 2 @PLGA MPs) is proposed for the local delivery of oxygen. By utilizing a series of methodologies, the impacts of each component used for MP fabrication on the oxygen release behavior and cytotoxicity of the CaO 2 + MnO 2 @ PLGA MPs are thoroughly investigated. Our analytical data obtained from in vitro studies indicate that the optimized CaO 2 + MnO 2 @PLGA MPs developed in this study can effectively relieve the hypoxia of preosteoblast MC3T3-E1 cells that are grown under low oxygen tension and promote their osteogenic differentiation, thus holding great promise in enhancing fractural healing by increasing tissue oxygenation.

Modulation of Inherent Niches in 3D Multicellular MSC Spheroids Reconfigures Metabolism and Enhances Therapeutic Potential

“…The discrimination between the investigated groups was thought to be attributed to the difference in the intrinsic gradients of oxygen, nutrients and signal molecules present in the spheroids [39,40]. Typically, as the spheroid size increases, the limited availability of oxygen owing to the increased diffusion distance is considered to mainly account for the development of a hypoxic core in spheroids, thereby altering cellular behaviors or even causing the death of interior cells [41][42][43]. In the present study, the largest MSC spheroids that were assembled by 80,000 cells and had a diameter of approximately 700 µm displayed, decreased mRNA expression of multiple therapeutic proteins, a finding that is consistent with a previous investigation.…”

Hypoxia in Bone and Oxygen Releasing Biomaterials in Fracture Treatments Using Mesenchymal Stem Cell Therapy: A Review

“…The use of oxygen-releasing peroxide on PLGA films for enhanced cell viability was also validated on a hypoxic fibroblast proliferation study in a 3D tissue-engineered constructs ( Oh et al, 2009 ). Researchers also developed an injectable composite system of PLGA encapsulated in calcium peroxide (CaO 2 )/manganese dioxide (MnO 2 ) microparticles ( Hsieh et al, 2020 ). Under low oxygen tension-induced cultures, they were able to promote the differentiation of pre-osteoblast cells.…”

Strontium Peroxide-Loaded Composite Scaffolds Capable of Generating Oxygen and Modulating Behaviors of Osteoblasts and Osteoclasts

“…Recently, calcium peroxide (CaO 2 )-based oxygen-generating biomaterials have been designed to improve local oxygen tension and support cell survival under hypoxic conditions [ 29 , 30 , 31 , 32 , 33 , 34 ]. The peroxide particles can react with water molecules, thus generating hydrogen peroxide (H 2 O 2 ) that can be decomposed into oxygen by using suitable catalysts [ 28 , 33 ].…”

“…The peroxide particles can react with water molecules, thus generating hydrogen peroxide (H 2 O 2 ) that can be decomposed into oxygen by using suitable catalysts [ 28 , 33 ]. In one of our previous works, manganese dioxide (MnO 2 ) was used as the catalyst, and both CaO 2 and MnO 2 powders were encapsulated into poly(lactic- co -glycolic acid) (PLGA) microparticles to control the reaction rate by limiting water infiltration [ 32 ]. The thus-developed injectable microparticles can serve as depots to release oxygen in a sustained manner and relieve cellular hypoxia [ 32 ].…”