Hongjin Qiu

The role of nanocomposites in bone regeneration

Tissue engineering utilizes the expertise within the fields of materials science, biology, chemistry, transplantation medicine, and engineering to design materials that can temporarily serve in a structural and/or functional capacity while a defect is regenerated. Of prominence in the realm of regenerative medicine is the issue of bone disease and degeneration, particularly among an increasingly aging population. Traditional methods for bone and joint replacement enjoy increasing success, but restoration of native tissue architecture remains the ideal. Toward this goal, the design of a tissue equivalent that can integrate with native bone must take into account the characteristics of this unique tissue. Firstly, the extracellular matrix of bone is a hierarchical, heterogeneous material that has features with sizes that range from the nanoscale to the macroscale. Secondly, there is synergy between these features that gives rise to a composite material with defined nano-, micro-, and macrophases. Understanding the role of these phases should lead to improved materials to aid bone regeneration. Emulating the structure of bone is difficult; nevertheless, researchers are developing nanocomposite materials that take us one step closer to attaining the mechanical and biological properties of bone. This article discusses the role of nanoscale parameters and interactions in bone and presents a few examples of how engineered nanocomposites attempt to mimic the hierarchical structure of bone in order to achieve tissue regeneration rather than repair.

Sustained transgene expression via citric acid-based polyester elastomers

Polymeric scaffolds are an important tool in tissue engineering and gene delivery using porous scaffolds can be a viable approach to control tissue response. Herein we describe the use of a biodegradable polyester elastomer, poly(1,8-octanediol-co-citrate) (POC), as a substrate for plasmid immobilization and cellular transfection of colonizing cells. Plasmid (pDNA), either complexed with poly(ethyleneimine) (PEI) forming polyplexes or in its native state, was surface-immobilized onto POC scaffolds via adsorption. Polyplex-containing scaffolds showed higher loading and slower initial rates of release than naked pDNA-containing scaffolds. Seeding of HEK293 cells and porcine aortic smooth muscle cells (PASMC) onto polyplex loaded-scaffolds demonstrated cell proliferation and transfection in vitro up to 12 days, significantly longer relative to bolus transfection. In vivo, transfection was evaluated using the mouse intraperitoneal (IP) fat model. In contrast to the in vitro study, successful long-term transgene delivery was only achieved with the naked pDNA-containing scaffolds. In particular, naked pDNA-containing scaffolds promoted high levels of both luciferase and green fluorescent protein (GFP) expression in vivo for 2 weeks. The results demonstrate that POC scaffolds are a suitable material for substrate-mediated gene delivery. POC scaffolds can potentially support long-term biological cues to mediate tissue formation through non-viral gene delivery.

Early tissue response to citric acid-based micro- and nanocomposites

Composites based on calcium phosphates and biodegradable polymers are desirable for orthopedic applications because of their potential to mimic bone. Herein, we describe the fabrication, characterization, and in vivo response of novel citric acid-based microcomposites and nanocomposites. Poly(1,8-octanediol-co-citrate) (POC) was mixed with increasing amounts of hydroxyapatite (HA) nanoparticles or microparticles (up to 60 wt %), and the morphology and mechanical properties of the resulting composites were assessed. To investigate tissue response, nanocomposites, microcomposites, POC, and poly(L-lactide) were implanted in osteochondral defects in rabbits and harvested at 6 weeks for histological evaluation. Scanning electron microscopy confirmed increased surface roughness of microcomposites relative to nanocomposites. The mechanical properties of both types of composites increased with increasing amounts of HA (8-328 MPa), although nanocomposites with 60 wt % HA displayed the highest strength and stiffness. Based on tissue-implant interfacial assessments, all implants integrated well with the surrounding bone and cartilage with no evidence of inflammation. Both nanocomposites and microcomposites supported bone remodeling; however, nanocomposites induced more trabecular bone formation at the tissue-implant interface. The mechanical properties of citric acid-based composites are within the range of human trabecular bone (1-1524 MPa, 211 ± 78 MPa mean modulus), and tissue response was dependent on the size and content of HA, providing new perspectives of design and fabrication criteria for orthopedic devices such as interference screws and fixation pins.

Nanocomposites for Regenerative Medicine

This chapter describes properties and applications of nanocomposites in tissue engineering and regenerative medicine with an emphasis on the impact of the nanophase on nanocomposite function. The nanophase can be used as a means to engineer new physical properties that improve the utility of tissue engineering scaffolds. Several examples of the use of the nanophase for mechanical reinforcement or drug delivery are discussed with an emphasis on understanding how nanoparticles are used to achieve the controlled release of macromolecules. Advances in nanotechnology, knowledge of mechanical reinforcement at the nanoscale level, and new strategies for controlled drug release will contribute to the next generation of nanocomposite-based scaffolds designed for regenerative medicine.

Erratum to “A citric acid-based hydroxyapatite composite for orthopedic implants”

We describe a novel approach to process bioceramic microparticles and poly(diol citrates) into bioceramic-elastomer composites for potential use in orthopedic surgery. The composite consists of the biodegradable elastomer poly(1,8-octanediol-citrate) (POC) and the bioceramic hydroxyapatite (HA). The objective of this work was to characterize POC-HA composites and assess the feasibility of fabricating tissue fixation devices using machining and molding techniques. The mechanical properties of POC-HA composites with HA (40, 50, 60, 65wt.%) were within the range of values reported for tissue fixation devices (for POC-HA 65wt.%, S(b)=41.4+/-3.1, E(b)=501.7+/-40.3, S(c)=74.6+/-9.0, E(c)=448.8+/-27.0, S(t)=9.7+/-2.3, E(t)=334.8+/-73.5, S(s)=27.7+/-2.4, T(s)=27.3+/-4.9, all values in MPa). At 20 weeks, the weight loss of POC-HA composites ranged between 8 and 12wt.%, with 65wt.% HA composites degrading the slowest. Exposure of POC-HA to simulated body fluid resulted in extensive mineralization in the form of calcium phosphate with Ca/P of 1.5-1.7 similar to bone. POC-HA supported osteoblast adhesion in vitro and histology results from POC-HA samples that were implanted in rabbit knees for 6 weeks suggest that the composite is biocompatible. Synthesis of POC-HA is easy and inexpensive, does not involve harsh solvents or initiators, and the mechanical properties of POC-HA with 65wt.% HA are suitable for the fabrication of potentially osteoconductive bone screws.

Erratum to “A citric acid-based hydroxyapatite composite for orthopedic implants”: [Biomaterials 27 (2006) 5845–5854]

We describe a novel approach to process bioceramic microparticles and poly(diol citrates) into bioceramic-elastomer composites for potential use in orthopedic surgery. The composite consists of the biodegradable elastomer poly(1,8-octanediol-citrate) (POC) and the bioceramic hydroxyapatite (HA). The objective of this work was to characterize POC-HA composites and assess the feasibility of fabricating tissue fixation devices using machining and molding techniques. The mechanical properties of POC-HA composites with HA (40, 50, 60, 65wt.%) were within the range of values reported for tissue fixation devices (for POC-HA 65wt.%, S(b)=41.4+/-3.1, E(b)=501.7+/-40.3, S(c)=74.6+/-9.0, E(c)=448.8+/-27.0, S(t)=9.7+/-2.3, E(t)=334.8+/-73.5, S(s)=27.7+/-2.4, T(s)=27.3+/-4.9, all values in MPa). At 20 weeks, the weight loss of POC-HA composites ranged between 8 and 12wt.%, with 65wt.% HA composites degrading the slowest. Exposure of POC-HA to simulated body fluid resulted in extensive mineralization in the form of calcium phosphate with Ca/P of 1.5-1.7 similar to bone. POC-HA supported osteoblast adhesion in vitro and histology results from POC-HA samples that were implanted in rabbit knees for 6 weeks suggest that the composite is biocompatible. Synthesis of POC-HA is easy and inexpensive, does not involve harsh solvents or initiators, and the mechanical properties of POC-HA with 65wt.% HA are suitable for the fabrication of potentially osteoconductive bone screws.

Erratum to "A citric acid-based hydroxyapatite composite for orthopedic implants". [Biomaterials 27 (2006) 5845-5854] (DOI: 10.1016/j.biomaterials.2006.07.042)

We describe a novel approach to process bioceramic microparticles and poly(diol citrates) into bioceramic-elastomer composites for potential use in orthopedic surgery. The composite consists of the biodegradable elastomer poly(1,8-octanediol-citrate) (POC) and the bioceramic hydroxyapatite (HA). The objective of this work was to characterize POC-HA composites and assess the feasibility of fabricating tissue fixation devices using machining and molding techniques. The mechanical properties of POC-HA composites with HA (40, 50, 60, 65wt.%) were within the range of values reported for tissue fixation devices (for POC-HA 65wt.%, S(b)=41.4+/-3.1, E(b)=501.7+/-40.3, S(c)=74.6+/-9.0, E(c)=448.8+/-27.0, S(t)=9.7+/-2.3, E(t)=334.8+/-73.5, S(s)=27.7+/-2.4, T(s)=27.3+/-4.9, all values in MPa). At 20 weeks, the weight loss of POC-HA composites ranged between 8 and 12wt.%, with 65wt.% HA composites degrading the slowest. Exposure of POC-HA to simulated body fluid resulted in extensive mineralization in the form of calcium phosphate with Ca/P of 1.5-1.7 similar to bone. POC-HA supported osteoblast adhesion in vitro and histology results from POC-HA samples that were implanted in rabbit knees for 6 weeks suggest that the composite is biocompatible. Synthesis of POC-HA is easy and inexpensive, does not involve harsh solvents or initiators, and the mechanical properties of POC-HA with 65wt.% HA are suitable for the fabrication of potentially osteoconductive bone screws.