Regenerative engineered vascularized bone mediated by calcium peroxide

Abstract

One of the main challenges hindering the clinical translation of bone tissue engineering scaffolds is the lack of establishment of functional vasculature. Insufficient vascularization and poor oxygen supply limit cell survival within the constructs resulting in poor osseointegration with the host tissue and eventually leading to inadequate bone regeneration. Inspired by cues from developmental biology, we regenerative engineered a composite matrix by incorporating calcium peroxide (CaO2) into poly(lactide‐co‐glycolide) (PLGA) microsphere‐based matrices and sought to assess whether the delivery of the byproducts of CaO2 decomposition, namely O2, Ca2+, and H2O2 could enhance the regeneration of vascularized bone tissue. The composite microspheres were successfully fabricated via the oil‐in‐water emulsion method. The presence and encapsulation of CaO2 was confirmed using scanning electron microscopy, energy dispersive x‐ray spectroscopy, thermogravimetric analysis, and X‐ray powder diffraction. The microspheres were further heat sintered into three‐dimensional porous scaffolds and characterized for their degradation and release of byproducts. The in vitro cytocompatibility of the matrices and their ability to support osteogenic differentiation was confirmed using human adipose‐derived stem cells. Lastly, an in vivo study was performed in a mouse critical‐sized calvarial defect model to evaluate the capacity of these matrices in supporting vascularized bone regeneration. Results demonstrated that the presence of CaO2 increased cellularization and biological activity throughout the matrices. There was greater migration of host cells to the interior of the matrices and greater survival and persistence of donor cells after 8 weeks, which in synergy with the composite matrices led to enhanced vascularized bone regeneration.

Robust phenotypic maintenance of limb cells during heterogeneous culture in a physiologically relevant polymeric-based constructed graft system

“…2I). The capacity of these sintered microsphere-based structures to support OBs growth, as well as bone regeneration has been well demonstrated in previous literature, making them an excellent choice for bone tissue regeneration applications 24,[34][35][36] .…”

“…Regenerative Engineering is an interdisciplinary field that has been defined as the Convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology, and Clinical Translation for the regeneration of complex tissues and organ systems 22 – 24 . At the forefront of this transdisciplinary approach is the study of epimorphic regeneration and understanding the morphogenetic cues involved in a regenerative limb to help develop translational strategies for tissue and organ regeneration 23 , 25 .…”

Local delivery to malignant brain tumors: potential biomaterial-based therapeutic/adjuvant strategies

“…Newland et al encapsulated CaO 2 into polyethylene glycol diacrylate (PEGDA) polymer using an emulsion and UV crosslinking technique. 125 Another two studies encapsulated CaO 2 into polytrimthylene carbonate 133 and PLGA 138 by conventional oil/oil and oil/water emulsions and solvent evaporation methods and both resulted in the prolonged release of oxygen for over 21 days. Such prolonged release of oxygen could be beneficial to overcome GBM hypoxia and enhance radiation efficacy which is administered over six weeks in the current radiation protocol.…”

Platelet‐rich plasma‐derived extracellular vesicles: A superior alternative in regenerative medicine?

“…As the human population continues to age and the incidence of degenerative and traumatic diseases continues to increase, developing therapeutic strategies to repair and regenerate damaged tissues and restore their normal functions is the most important goal of regenerative medicine 1 . To date, the strategies of regenerative medicine have focused on using materials science and engineering techniques to develop novel biomaterials that can regulate cellular functions and activate their innate regenerative potential 2–4 . However, in recent decades, the potential of platelet‐rich plasma (PRP) therapies has attracted considerable interest in regenerative medicine.…”

“… 1 To date, the strategies of regenerative medicine have focused on using materials science and engineering techniques to develop novel biomaterials that can regulate cellular functions and activate their innate regenerative potential. 2 , 3 , 4 However, in recent decades, the potential of platelet‐rich plasma (PRP) therapies has attracted considerable interest in regenerative medicine. Many high‐quality systematic reviews and meta‐analyses have summarized the encouraging results of PRP therapies in a wide range of clinical fields, including orthopaedic surgery, 5 plastic surgery, 6 dermatology, 7 trichology, 8 , 9 cardiac surgery, 10 maxillofacial surgery, 11 pain management, 12 spinal disorders, 13 sports medicine 14 and others.…”