Engineering three-dimensional (3D) tissues in clinically relevant sizes have demonstrated to be an effective solution to bridge the gap between organ demand and the dearth of compatible organ donors. A major challenge to the clinical translation of tissue-engineered constructs is the lack of vasculature to support an adequate supply of oxygen and nutrients post-implantation. Previous efforts to improve the vascularization of engineered tissues have not been commensurate to meeting the oxygen demands of implanted constructs during the process of homogeneous integration with the host. Maintaining cell viability and metabolic activity during this period is imperative to the survival and functionality of the engineered tissues. As a corollary, there has been a shift in the scientific impetus beyond improving vascularization. Strategies to engineer biomaterials that encapsulate cells and provide the sustained release of oxygen over time are now being explored. This review summarizes different types of oxygen-releasing biomaterials, strategies for their fabrication, and approaches to meet the oxygen requirements in various tissue engineering applications, including cardiac, skin, bone, cartilage, pancreas, and muscle regeneration.

Hydrogel-based biomimetic scaffolds have generated broad interest due to their tunable physical, chemical, and biological properties for bone tissue engineering applications. We fabricated eggshell microparticle (ESP) reinforced gelatin-based hydrogels to obtain mechanically stable and biologically active three-dimensional (3D) constructs that can differentiate pre-mature cells into osteoblasts. Physical properties including swelling ratio, degradation, and mechanical properties of the composite hydrogels were investigated. Pre-osteoblasts were encapsulated within the ESP-reinforced hydrogels to study their differentiation and evaluate mineral deposition by these cells. The ESP-reinforced gels were then subcutaneously implanted in a rat model to determine their biocompatibility and degradation behaviors. The composite hydrogels have shown outstanding tunability in physical and biological properties holding substantial promise for engineering mineralized tissues (e.g. bone, cartilage, tooth, and tendon). These 3D scaffolds enabled the differentiation of pre-osteoblasts without the use of specialized osteogenic growth medium. The ESP-reinforced gels exhibited significant enhancement in mineralization by pre-osteoblasts. These behaviors are positively correlated with increasing concentrations of ESP. Findings suggest that our novel composite hydrogel exhibits superior mechanical properties and indicates a favorable in vivo response by subcutaneous implantation in a rat model.

Protein-based biomaterials are widely used to generate three-dimensional (3D) scaffolds for tissue regeneration as well as compact delivery systems for drugs, genes, and peptides. Specifically, albumin-based biomaterials are of particular interest for their ability to facilitate controlled delivery of drugs and other therapeutic agents. These hydrogels possess non-toxic and non-immunogenic properties that are desired in tissue engineering scaffolds. This work employs a rapid ultraviolet (UV) light induced crosslinking to fabricate bovine serum albumin (BSA) hydrogels. Using four different conditions, the BSA hydrogel properties were modulated based on the extent of glycidyl methacrylate modification in each polymer. The highly tunable mechanical behavior of the material was determined through compression tests which yielded a range of material strengths from 4.4 ± 1.5 to 122 ± 7.4 kPa. Pore size measurements also varied from 7.7 ± 1.7 to 23.5 ± 6.6 μm in the photocrosslinked gels. The physical properties of materials such as swelling and degradation were also characterized. In further evaluation, 3D scaffolds were used in cell encapsulation and in vivo implantation studies. The biocompatibility and degradability of the material demonstrated effective integration with the native tissue environment. These modifiable chemical and mechanical properties allow BSA hydrogels to be fine-tuned to a plethora of biomedical applications including regenerative medicine, in vitro cancer study models, and wound healing approaches.

Recent innovations in bone tissue engineering have introduced biomaterials that generate oxygen to substitute vasculature. This strategy provides the immediate oxygen required for tissue viability and graft maturation. Here we demonstrate a novel oxygen-generating tissue scaffold with predictable oxygen release kinetics and modular material properties. These hydrogel scaffolds were reinforced with microparticles comprised of emulsified calcium peroxide (CaO₂) within polycaprolactone (PCL). The alterations of the assembled materials produced constructs within 5 ± 0.81 kPa to 34 ± 0.9 kPa in mechanical strength. The mass swelling ratios varied between 11% and 25%. Our in vitro and in vivo results revealed consistent tissue viability, metabolic activity, and osteogenic differentiation over two weeks. The optimized in vitro cell culture system remained stable at pH 8–9. The in vivo rodent models demonstrated that these scaffolds support a 70 mm³ bone volume that was comparable to the native bone and yielded over 90% regeneration in critical size cranial defects. Furthermore, the in vivo bone remodeling and vascularization results were validated by tartrate-resistant acid phosphatase (TRAP) and vascular endothelial growth factor (VEGF) staining. The promising results of this work are translatable to a repertoire of regenerative medicine applications including advancement and expansion of bone substitutes and disease models.