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Review
, 109 (8), 1898-911

Engineering Biomaterials to Integrate and Heal: The Biocompatibility Paradigm Shifts

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Review

Engineering Biomaterials to Integrate and Heal: The Biocompatibility Paradigm Shifts

James D Bryers et al. Biotechnol Bioeng.

Abstract

This article focuses on one of the major failure routes of implanted medical devices, the foreign body reaction (FBR)--that is, the phagocytic attack and encapsulation by the body of the so-called "biocompatible" biomaterials comprising the devices. We then review strategies currently under development that might lead to biomaterial constructs that will harmoniously heal and integrate into the body. We discuss in detail emerging strategies to inhibit the FBR by engineering biomaterials that elicit more biologically pertinent responses.

Figures

Figure 1
Figure 1
The general timeline of the cellular response against implanted biomaterials (Anderson, 2001).
Figure 2
Figure 2
Inducers and responses of different polarized MØ populations. MØ exposure to IFN-g and LPS drives M1 polarization, with potentiated cytotoxic and antitumoral properties, whereas M2-MØ are more prone to immuno-regulatory and protumoral activities. M2a- (induced by IL-4 and IL-13) and M2b-MØ (induced by immune complexes and TLR or IL-1R agonists) exert immunore-gulatory functions and drive type II responses, whereas M2c macrophages (induced by IL-10) are more related to suppression of immune responses and tissue remodeling. DTH, delayed-type hypersensitivity; IC, immune complexes; IFN-g, interferon-g; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; MR, mannose receptor; PTX3, the long pentraxin PTX3; RNi, reactive nitrogen intermediates; ROi, reactive oxygen intermediates; SLAM, signaling lymphocytic activation molecule; SRs, scavenger receptors; TLR, Toll-like receptor. After Mantovani et al. (2004).
Figure 3
Figure 3
Thirty five-micrometer pore size pHEMA sphere templated scaffold; scale bar =50 μm (left), scale bar =300 μm (right).
Figure 4
Figure 4
Survival and vascularization at 1 week of rat cardiomyocyte-seeded pHEMA 35 μm construct implanted subcutaneously. A: sarcomeric actin. B: rat endothelial cell antigen-1.
Figure 5
Figure 5
Intra-pore vascular density after 4 weeks of subcutaneous implantation varies with pore size.
Figure 6
Figure 6
MØ infiltration in PTSs of different pore size; MØ stained with BM8 Mab marker (Fukano et al., 2010).
Figure 7
Figure 7
pHEMA 35-μm pore PTS implanted in dorsal murine model transcutaneously, regenerating dermis and epidermis layers (Fukano et al., 2010).
Figure 8
Figure 8
A: Rabbit femur bone growing into the PTS (uninjured bone adjacent to the implant is at the top of the image). B: Control shows no bone tissue in-growth. C: Micro CT data on bone regrowth at 4 weeks.
Figure 9
Figure 9
Macrophage phenotype in response to 4-week myocardial implants in Sprague–Dawley rats. Inset: Total MØ were identified with CD68+ staining (red). M1 and M2 phenotypes were determined by NOS2 (green) and MMR (blue), respectively. Overlayed images of CD68, NOS2, and MMR were analyzed to determine MØ phenotype. A majority of MØ in the porous implants expressed both NOS2 and MMR, although NOS2+/MMR− (darts) and NOS2−/MMR+ (arrows) MØ could be identified. MØ typically adhered to the material. The fraction of each activated state was determined for CD68+ MØ with significant increase in NOS2+/MMR+ MØ at all porous implant sites (n =4; P <0.05). There is a trend of increased NOS2−/MMR+ MØ in 40-μm porous constructs versus non-porous (P =0.06). Scale bar: 50 μm. (Madden et al., 2010).
Figure 10
Figure 10
C57/Bl6 normal mouse implanted transcutaneously with poly(HEMA) porous construct; 35 μm pore size. Construct retrieved after 14 days; examined by TEM; cells colorized digitally (Fukano et al., 2010).

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