Nanomedicine: Nanotechnology, Biology and Medicine
Original ArticleIn vivo bone formation by and inflammatory response to resorbable polymer-nanoclay constructs
Graphical Abstract
Nanocomposite materials consisting of organo-modified Montmorillonite clays (nanoclay) dispersed in resorbable polymer matrices via supercritical carbon dioxide (scCO2) processing have demonstrated surprising structural and compressive mechanical properties that make them candidates for bone graft substitute applications. In the present study, we demonstrate that these highly porous constructs exhibit the ability to facilitate in vivo, growth factor-induced bone formation. The in vivo inflammatory response elicited by the nanoclay-loaded constructs was similar to more traditional hydroxyapatite-based composite materials.
Section snippets
Preparation of PDLA and PDLA-Nanoclay Debris for Inflammation Study
The inflammatory response to, and osteolytic potential of PDLA-nanoclay particulate debris was investigated, and compared to both pure PDLA, as well as PDLA filled with hydroxyapatite. Hydroxyapatite (Ca10(PO4)6(OH)2, Sigma-Aldrich) is a calcium phosphate material which has been traditionally used as a functional filler material in hard tissue engineering constructs and bone graft substitute materials.4, 7, 13, 16, 23, 24, 26, 41 As a secondary objective, two different types of nanoclay
Inflammatory Response to Nanocomposite Particulate
Given the relative lack of in vivo data regarding the inflammatory response of nanoclay and nanoclay-containing materials, a study was undertaken to characterize the response to PDLA-nanoclay constructs in particulate form. This particulate form was chosen over bulk constructs in an effort to simulate the potential shedding of nanocomposites debris during biomechanical loading and hydrolytic degradation of the constructs in vivo. The response to PDLA constructs containing one of two different
Discussion
The structural, mechanical and biologic constraints placed on bone graft substitute materials represent a significant challenge to researchers and physicians. These constructs must support significant biomechanical loads during activities of daily living, despite having an interconnected porous morphology with average pore diameters ranging from 100-300 μm.1, 2, 3 Resorbable polymers, especially lactic and glycolic acid-based materials, have been thoroughly studied as candidates for bone graft
Acknowledgment
The authors dedicate this manuscript to the memory of Harry N. Herkowitz, M.D., former Chairman of the Department of Orthopaedic Surgery at William Beaumont Hospital 1991-2013.
References (65)
- et al.
Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering
Biomaterials
(2006) - et al.
Structure and mechanical properties of supercritical carbon dioxide processed porous resorbable polymer constructs
J Mech Behav Biomed Mater
(2009) - et al.
Supercritical carbon dioxide processed resorbable polymer nanocomposite bone graft substitutes
Acta Biomater
(2011) - et al.
Long-term in vitro degradation of PDLLA/bioglass bone scaffolds in acellular simulated body fluid
Acta Biomater
(2011) - et al.
A biodegradable porous composite scaffold of PGA/beta-TCP for bone tissue engineering
Bone
(2010) - et al.
In vitro cell performance on hydroxyapatite particles/poly(l-lactic acid) nanofibrous scaffolds with an excellent particle along nanofiber orientation
Acta Biomater
(2011) - et al.
Bone regeneration using a microstereolithography-produced customized poly(propylene fumarate)/diethyl fumarate photopolymer 3D scaffold incorporating BMP-2 loaded PLGA microspheres
Biomaterials
(2011) - et al.
Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering
Bone
(2008) - et al.
Monolithic and assembled polymer-ceramic composites for bone regeneration
Acta Biomater
(2013) - et al.
Role of polymer-clay interactions and nanoclay dispersion on the viscoelastic response of supercritical CO2 dispersed PVME-clay nanocomposites
Polymer
(2009)
Clay enriched silk biomaterials for bone formation
Acta Biomater
Co-Cr-Mo alloy particles induce tumor necrosis factor alpha production in MLO-Y4 osteocytes: a role for osteocytes in particle-induced inflammation
Bone
Inflammatory responses to orthopaedic biomaterials in the murine air pouch
Biomaterials
Diverse cellular and apoptotic responses to variant shapes of UHMWPE particles in a murine model of inflammation
Biomaterials
Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly(l-lactic-co-glycolic acid) scaffold
Biomaterials
The effect of spinal instrumentation particulate wear debris: an in vivo rabbit model and applied clinical study of retrieved instrumentation cases
Spine J
The role of macrophages in osteolysis of total joint replacement
Biomaterials
Association between UHMWPE particle-induced inflammatory osteoclastogenesis and expression of RANKL, VEGF, and Flt-1 in vivo
Biomaterials
The potential role of the osteoblast in the development of periprosthetic osteolysis: review of in vitro osteoblast responses to wear debris, corrosion products, and cytokines and growth factors
J Arthroplast
Inflammatory cell response to calcium phosphate biomaterial particles: an overview
Acta Biomater
Effect of silicon level on rate, quality and progression of bone healing within silicate-substituted porous hydroxyapatite scaffolds
Biomaterials
Current status of bone graft options for anterior interbody fusion of the cervical and lumbar spine
Neurosurg Rev
Tissue engineering of bone: material and matrix considerations
J Bone Joint Surg Am
Can we improve fixation and outcomes? Use of bone substitutes
J Orthop Trauma
Heterotopic bone formation by nano-apatite containing poly(d,l-lactide) composites
Eur Cell Mater
Polylactic acid-phosphate glass composite foams as scaffolds for bone tissue engineering
J Biomed Mater Res B Appl Biomater
BMP-2/PLGA delayed-release microspheres composite graft, selection of bone particulate diameters, and prevention of aseptic inflammation for bone tissue engineering
Ann Biomed Eng
Novel porous scaffolds of poly(lactic acid) produced by phase-separation using room temperature ionic liquid and the assessments of biocompatibility
J Mater Sci Mater Med
Preparation and characterization of a highly macroporous biodegradable composite tissue engineering scaffold
J Biomed Mater Res A
Polycaprolactone scaffolds fabricated with an advanced electrohydrodynamic direct-printing method for bone tissue regeneration
Biomacromolecules
Polycaprolactone/hydroxyapatite composite scaffolds: preparation, characterization, and in vitro and in vivo biological responses of human primary bone cells
J Biomed Mater Res A
Response of human embryonic stem cell-derived mesenchymal stem cells to osteogenic factors and architectures of materials during in vitro osteogenesis
Tissue Eng A
Cited by (8)
Polymer nanocomposites based on two-dimensional nanomaterials
2019, Two-Dimensional Nanostructures for Biomedical Technology: A Bridge between Material Science and BioengineeringBionanocomposites
2017, Clay-Polymer NanocompositesPolymers and Composites for Orthopedic Applications
2017, Materials and Devices for Bone DisordersOsteoconductive composite graft based on bacterial synthesized hydroxyapatite nanoparticles doped with different ions: From synthesis to in vivo studies
2016, Nanomedicine: Nanotechnology, Biology, and MedicineCitation Excerpt :However, only immature bone tissue (also called woven bone) and red blood cells (RBC) can be seen in tissue/control graft section at the same period of time (Figure 5, IV.B).7 Moreover, no aggregation of inflammatory cells such as white blood cells (WBC), macrophage or epithelioid cells were recognized in both magnified sections.24,25 A least square surgical procedure on degradation behavior of the grafts (see Figures S3-5 in supplementary data file) shows complete degradation of CZM-HA graft compared with the control graft after 4 weeks of implantation.
Biofabrication of the osteochondral unit and its applications: Current and future directions for 3D bioprinting
2022, Journal of Tissue EngineeringNanoclay Reinforced Biomaterials for Mending Musculoskeletal Tissue Disorders
2021, Advanced Healthcare Materials
The authors declare no conflicts of interest with regard to the conduct of experiments or preparation of the present manuscript. Funding for this research was provided by a Seed/Starter Research Grant from the Cervical Spine Research Society, as well as a resident research grant from the Beaumont Research Institute.