The effect of mesenchymal stem cells delivered via hydrogel-based tissue engineered periosteum on bone allograft healing

Abstract

Allografts remain the clinical “gold standard” for treatment of critical sized bone defects despite minimal engraftment and ~60% long-term failure rates. Therefore, the development of strategies to improve allograft healing and integration are necessary. The periosteum and its associated stem cell population, which are lacking in allografts, coordinate autograft healing. Herein we utilized hydrolytically degradable hydrogels to transplant and localize mesenchymal stem cells (MSCs) to allograft surfaces, creating a periosteum mimetic, termed a ‘tissue engineered periosteum’. Our results demonstrated that this tissue engineering approach resulted in increased graft vascularization (~2.4-fold), endochondral bone formation (~2.8-fold), and biomechanical strength (1.8-fold), as compared to untreated allografts, over 16 weeks of healing. Despite this enhancement in healing, the process of endochondral ossification was delayed compared to autografts, requiring further modifications for this approach to be clinically acceptable. However, this bottom-up biomaterials approach, the engineered periosteum, can be augmented with alternative cell types, matrix cues, growth factors, and/or other small molecule drugs to expedite the process of ossification.

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

“…27 PEG hydrogels are traditionally formed through radicalmediated photopolymerizations, 28,29 which allow for rapid fabrication into geometries dictated by custom molds in vitro or to match tissue defects in vivo. 30,31 PEG hydrogels have been utilized successfully to culture and control the behavior of various cell types, including MSCs, 32,33 chondrocytes, [34][35][36] osteoblasts, 37 pancreatic b-islet cells, 38,39 and neurons. 40,41 In addition, recent work has demonstrated the ability of PEG hydrogels to provide spatiotemporal control of MSC delivery in vivo to promote bone regeneration.…”

“…40,41 In addition, recent work has demonstrated the ability of PEG hydrogels to provide spatiotemporal control of MSC delivery in vivo to promote bone regeneration. 31,42,43 In this work, methods have been explored to encapsulate, culture, and characterize primary SMG cells within PEG hydrogels, with the long-term goal of developing a tissue engineering approach for the salivary gland. Due to the sensitivity of salivary gland cells to reactive oxygen species (ROS), [44][45][46][47][48] we examined the effects of two forms of radical-mediated hydrogel polymerization: chain addition methacrylate-based polymerizations and step-growth thiol-ene polymerizations on primary SMG cells.…”

“…Previous work using a PEG hydrogel periosteum mimetic to deliver MSCs significantly improved bone healing in a segmental defect model. 31,42 Critical to this approach was the localization and temporal release of MSCs provided by the PEG hydrogel, 43 as MSCs seeded directly on an allograft have little effect on healing. [107][108][109] In previous studies, transplantation of primary SMG cells into irradiated glands was performed using intraglandular *5-10 mL injections.…”

Microwave-assisted Functionalization of Poly(ethylene glycol) and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation

“…For example, chain-growth polymerized PEGDM networks have been demonstrated as well suited to control cell localization in the development of a tissue-engineered periosteum 18,19 . If the research question will be best addressed by the use of step-growth hydrogels, Fairbanks et al provides a detailed description of the norbornene functionalization strategy for PEG 7 .…”

A bio-artificial poly([D,L]-lactide-co-glycolide) drug-eluting nanofibrous periosteum for segmental long bone open fractures with significant periosteal stripping injuries

“…Few publications address the concerns associated with the management of the periosteum during the treatment of open fractures. 10 An ideal biomimetic periosteum would provide delivery of osteoinductive growth factors, restore angiogenic potential, and inhibit microbial infection on the bone surface, to allow better bone union. 11,12 For those open fractures with comminuted fracture fragments, we also expect that the biomimetic periosteum can provide some mechanical strength for seizing the isolated bone fragments to decrease the fragmental irritated fracture pain and decrease nonunion due to excessive micro-motions between fracture fragments.…”