Effects of sterilization on an extracellular matrix scaffold: Part I. Composition and matrix architecture

The impact of peracetic acid (PAA), lyophilization, and ethylene oxide (EO) sterilization on the composition and three dimensional matrix structure of small intestinal submucosa (SIS), a biologic scaffold used to stimulate the repair of damaged tissues and organs, was examined. Fibronectin and glycosaminoglycans are retained in SIS following oxidation by peracetic acid and alkylation using ethylene oxide gas. Significant amounts of FGF-2 are also retained, but VEGF is susceptible to the effects of PAA and is dramatically reduced following processing. Further, matrix oxidation, lyophilization, and sterilization with EO can be performed without irreversibly collapsing the three dimensional structure of the native SIS. These structural features and growth promoting extracellular matrix constituents are likely to be important variables underlying cellular attachment, infiltration and eventual incorporation of SIS into healing host tissues.     

Bioactive materials for tissue engineering, regeneration and repair

Tissue engineering is an interdisciplinary field which applies the principles of engineering and the life sciences to the design, construction, modification, growth and maintenance of living tissues [1, 2]. One of two approaches can be taken: (1) in vitro construction of bioartificial tissues from cells seeded onto a resorbable scaffold or (2) in vivo modification of cell growth and function to stimulate tissue regeneration [2, 3]. This concept represents a shift in emphasis from replacement to regeneration of diseased or damaged tissues, in which the development of bioactive materials has played a significant role.This paper will begin with an overview of the use of biomaterials as implants and their limitations, leading to the reasons for the dramatic shift in focus regarding the approach to repairing damaged tissues. The majority of the paper will discuss the ways in which biomaterials can be developed to implement the concept of tissue engineering. Finally, the implications of these developments for future treatment of damaged or diseased tissues will be considered.     

Fabrication and characterization of bioactive silk fibroin/wollastonite composite scaffolds

Composite scaffolds of silk fibroin (SF) with bioactive wollastonite were prepared by freeze-drying. X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy analysis showed that random coil and β-sheet structure co-existed in the SF scaffold. The mechanical performance, surface hydrophilicity and water-uptake capacity of the composite scaffolds were improved compared with those of pure SF scaffold. The bioactivity of the composite scaffold was evaluated by soaking in a simulated body fluid (SBF), and formation of a hydroxycarbonate apatite (HCA) layer was determined by FT-IR and XRD. The results showed that the SF/wollastonite composite scaffold was bioactive as it induced the formation of HCA on the surface of the composite scaffold after soaking in SBF for 5 days. In vitro cell attachment and proliferation tests showed that the composite scaffold was a good matrix for the growth of L929 mouse fibroblast cells. Consequently, the incorporation of wollastonite into the SF scaffold can enhance both the mechanical strength and bioactivity of the scaffold, which suggests that the SF/wollastonite composite scaffold may be a potential biomaterial for tissue engineering.     

Growth of fibroblast and vascular smooth muscle cells in fibroin/collagen scaffold

In our recent study, a novel fibroin/collagen scaffold with improved mechanical properties and controllable porous structure was prepared through freeze–drying method. In this research, the cyto-compatibility was further studied, using fibroblast and vascular smooth muscle cells (VSMC) as the model cells. MTT results indicated that the growth of fibroblast and VSMC both further improved in the fibroin/collagen scaffold than in pure fibroin scaffolds. The confocal and SEM results showed that fibroblast cells and VSMCs had better adhesion and spreading properties in the fibroin/collagen scaffolds. Although further studies, such as the extracellular matrix production and the functional gene expression, are necessary to clarify the biocompatibility of the fibroin/collagen scaffolds, the present results indicate that the fibroin/collagen scaffold is a new scaffold material suitable for tissue engineering. On the other hand, the mild and all-aqueous preparation processes also make it possible to embed different growth factors inside the scaffolds to maximize cell functions and the formation of specific tissues.     

Loading of VEGF to the heparin cross-linked demineralized bone matrix improves vascularization of the scaffold

Deficient vascularization is one of the prominent shortcomings of porous tissue-engineering scaffolds, which results in insufficient oxygen and nutrients transportation. Here, heparin cross-linked demineralized bone matrices (HC-DBM) pre-loaded with vascular endothelial growth factor (VEGF) were designed to promote cells and new microvessels invasion into the matrices. After being chemical crosslinked with heparin by N-hydroxysuccinimide and N-(3-di-methylaminopropyl)-N’-ethylcarbodiimide, the scaffold could bind more VEGF than the non-crosslinked one and achieve localized and sustained delivery. The biological activity of VEGF binding on heparinized collagen was demonstrated by promoting endothelial cells proliferation. Evaluation of the angiogenic potential of heparinized DBM loaded with VEGF was further investigated by subcutaneous implantation. Improved angiogenesis of heparinized DBM loaded with VEGF was observed from haematoxylin-eosin staining and immunohistochemistry examination. The results demonstrated that heparin cross-linked DBM binding VEGF could be a useful strategy to stimulate cells and blood vessels invasion into the scaffolds.     

Repair of experimental Achilles tenotomy with porcine renal capsule material in a rat model

Porcine small intestinal submucosa (SIS) is a collagenous acellular matrix which has found substantial utility as a tissue growth scaffold. In the present study, the utility of porcine renal capsule matrix (RCM) was compared to SIS in a rat Achilles tenotomy repair model. Groups of rats underwent surgical tenotomy followed by either no repair, repair with a SIS graft, or repair with a RCM graft. The weight-bearing ability of the manipulated limb was evaluated for 10 days following surgery using a subjective scale. Tenotomy sites sampled 28 days after surgery were numerically graded for degree of histologic change. There were no statistically significant differences between groups with respect to return to weight-bearing ability (p ≥ 0.05) or degree of histologic change (p ≥ 0.001); however, a non-significant trend suggested that rats treated with SIS or RCM experienced a faster return to limb function than untreated rats, and RCM-treated rats had slightly higher scores for degree of histologic change, suggesting a more rapid repair of the tenotomy site than in SIS-treated or untreated rats. The harvested tenotomy sites in all treatment groups were characterized by marked fibroplasia and presence of macrophages. Remnants of SIS surrounded by macrophages and multi-nucleated giant cells were still present in some rats, however remnants of RCM were not observed, suggesting more rapid incorporation of RCM. The results show that RCM is equivalent to SIS as a material for repair of Achilles tendon injury and merits further study in other tendon injury models.     

Mechanical Cues Regulating Proangiogenic Potential of Human Mesenchymal Stem Cells through YAP‐Mediated Mechanosensing

Stem cells secrete trophic factors that induce angiogenesis. These soluble factors are promising candidates for stem cell–based therapies, especially for cardiovascular diseases. Mechanical stimuli and biophysical factors presented in the stem cell microenvironment play important roles in guiding their behaviors. However, the complex interplay and precise role of these cues in directing pro‐angiogenic signaling remain unclear. Here, a platform is designed using gelatin methacryloyl hydrogels with tunable rigidity and a dynamic mechanical compression bioreactor to evaluate the influence of matrix rigidity and mechanical stimuli on the secretion of pro‐angiogenic factors from human mesenchymal stem cells (hMSCs). Cells cultured in matrices mimicking mechanical elasticity of bone tissues in vivo show elevated secretion of vascular endothelial growth factor (VEGF), one of representative signaling proteins promoting angiogenesis, as well as increased vascularization of human umbilical vein endothelial cells (HUVECs) with a supplement of conditioned media from hMSCs cultured across different conditions. When hMSCs are cultured in matrices stimulated with a range of cyclic compressions, increased VEGF secretion is observed with increasing mechanical strains, which is also in line with the enhanced tubulogenesis of HUVECs. Moreover, it is demonstrated that matrix stiffness and cyclic compression modulate secretion of pro‐angiogenic molecules from hMSCs through yes‐associated protein activity.     

A 3D biodegradable protein based matrix for cartilage tissue engineering and stem cell differentiation to cartilage

A protein based 3D porous scaffold is fabricated by blending gelatin and albumin. The biomimetic biodegradable gelatin, promoted good cell adhesion and its hydrophilic nature enabled absorption of culture media. Albumin is proposed to serve as a nontoxic foaming agent and also helped to attain a hydrophobic-hydrophilic balance. The hydrophobic-hydrophilic balance and appropriate crosslinking of the scaffold avoided extensive swelling, as well as retained the stability of scaffold in culture medium for long period. The scaffold is found to be highly porous with open interconnected pores. The adequate swelling and mechanical property of the scaffold helped to withstand the loads imparted by the cells during in vitro culture. The scaffold served as a nontoxic material to monolayer of fibroblast cells and is found to be cell compatible. The suitability of scaffold for chondrocyte culture and stem cell differentiation to chondrocytes is further explored in this work. The scaffold provided appropriate environment for chondrocyte culture, resulting in deposition of cartilage specific matrix molecules that completely masked the pores of the porous scaffold. The scaffold promoted the proliferation and differentiation of mesenchymal stem cells to chondrocytes in presence of growth factors. The transforming growth factor, TGFbeta3 promoted better chondrogenic differentiation than its isoform TGFbeta1 in this scaffold.     

Application of strontium-doped calcium polyphosphate scaffold on angiogenesis for bone tissue engineering

The key factor for regenerating large segmental bone defects through bone tissue engineering is angiogenesis in scaffolds. Attempts to overcome this problem, it is a good strategy to develop a new scaffold with bioactivity to induce angiogenesis in bone tissue engineering. In our previous research, the ability of strontium-doped calcium polyphosphate (SCPP) to stimulate the release of angiogenic growth factors from cultured osteoblasts was studied. This study was performed to determine the ability of SCPP to induce angiogenesis within in vitro co-culture model of human umbilical vein endothelial cells (HUVEC) and osteoblasts co-cultured. The bioactivity of developed scaffolds to induce angiogenesis in vivo was also researched in this paper. Co-cultured model has been developed in vitro and then cultured with SCPP scaffold as well as calcium polyphosphate (CPP) scaffold and hydroxylapatite (HA) scaffold. The results showed that the optimal ratio of HUVEC and osteoblasts co-cultured model for in vitro angiogenesis was 5:1. The model could maintain for more than 35 days when cultured with the scaffold and show the best activity at 21st day. Compared with those in CPP and HA scaffold, the formation of tube-like structure and the expression of platelet endothelial cell adhesion molecule in co-cultured model is better in SCPP scaffold. The in vivo immunohistochemistry staining for VEGF also showed that SCPP had a potential to promote the formation of angiogenesis and the regeneration of bone. SCPP scaffold could be served as a potential biomaterial with stimulating angiogenesis in bone tissue engineering and bone repair.     

Cell and biomolecule delivery for regenerative medicine

Abstract

Regenerative medicine is an exciting field that aims to create regenerative alternatives to harvest tissues for transplantation. In this approach, the delivery of cells and biological molecules plays a central role. The scaffold (synthetic temporary extracellular matrix) delivers cells to the regenerative site and provides three-dimensional environments for the cells. To fulfil these functions, we design biodegradable polymer scaffolds with structural features on multiple size scales. To enhance positive cell–material interactions, we design nano-sized structural features in the scaffolds to mimic the natural extracellular matrix. We also integrate micro-sized pore networks to facilitate mass transport and neo tissue regeneration. We also design novel polymer devices and self-assembled nanospheres for biomolecule delivery to recapitulate key events in developmental and wound healing processes. Herein, we present recent work in biomedical polymer synthesis, novel processing techniques, surface engineering and biologic delivery. Examples of enhanced cellular/tissue function and regenerative outcomes of these approaches are discussed to demonstrate the excitement of the biomimetic scaffold design and biologic delivery in regenerative medicine.     

Mineralization of osteoblasts with electrospun collagen/hydroxyapatite nanofibers

Regeneration of fractured or diseased bones is the challenge faced by current technologies in tissue engineering. The major solid components of human bone consist of collagen and hydroxyapatite. Collagen (Col) and hydroxyapatite (HA) have potential in mimicking natural extracellular matrix and replacing diseased skeletal bones. More attention has been focused on HA because of its crystallographic structure similar to inorganic compound found in natural bone and extensively investigated due to its excellent biocompatibility, bioactivity and osteoconductivity properties. In the present study, electrospun nanofibrous scaffolds are fabricated with collagen (80 mg/ml) and Col/HA (1:1). The diameter of the collagen nanofibers is around 265 ± 0.64 nm and Col/HA nanofibers are 293 ± 1.45 nm. The crystalline HA (29 ± 7.5 nm) loaded into the collagen nanofibers are embedded within nanofibrous matrix of the scaffolds. Osteoblasts cultured on both scaffolds and show insignificant level of proliferation but mineralization was significantly (p < 0.001) increased to 56% in Col/HA nanofibrous scaffolds compared to collagen. Energy dispersive X-ray analysis (EDX) spectroscopy results proved the presence of higher level of calcium and phosphorous in Col/HA nanocomposites than collagen nanofibrous scaffolds grown osteoblasts. The results of the present study suggested that the designed electrospun nanofibrous scaffold (Col/HA) have potential biomaterial for bone tissue engineering.     

Emulsion electrospun vascular endothelial growth factor encapsulated poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactic acid-<Emphasis Type="Italic">co</Emphasis>-ε-caprolactone) nanofibers for sustained release in cardiac tissue engineering

Emulsion electrospinning is a novel approach to fabricate core–shell nanofibers, and it is associated with several advantages such as the alleviation of initial burst release of drugs and it protects the bioactivity of incorporated drugs or proteins. Aiming to develop a sustained release scaffold which could be a promising substrate for cardiovascular tissue regeneration, we encapsulated vascular endothelial growth factor (VEGF) with either of the protective agents, dextran or bovine serum albumin (BSA) into the core of poly(l-lactic acid-co-ε-caprolactone) (PLCL) nanofibers by emulsion electrospinning. The morphologies and fiber diameters of the emulsion electrospun scaffolds were determined by scanning electron microscope, and the core–shell structure was evaluated by laser scanning confocal microscope. Uniform nanofibers of PLCL, PLCL–VEGF–BSA, and PLCL–VEGF–DEX with fiber diameters in the range of 572 ± 92, 460 ± 63, and 412 ± 61 nm, respectively were obtained by emulsion spinning. The release profile of VEGF in phosphate-buffered saline for up to 672 h (28 days) was evaluated, and the scaffold functionality was established by performing cell proliferations using human bone marrow derived mesenchymal stem cells. Results of our study demonstrated that the emulsion electrospun VEGF containing core–shell structured PLCL nanofibers offered controlled release of VEGF through the emulsion electrospun core–shell structured nanofibers and could be potential substrates for cardiac tissue regeneration.     

Rapid biofabrication of tubular tissue constructs by centrifugal casting in a decellularized natural scaffold with laser-machined micropores

Centrifugal casting allows rapid biofabrication of tubular tissue constructs by suspending living cells in an in situ cross-linkable hydrogel. We hypothesize that introduction of laser-machined micropores into a decellularized natural scaffold will facilitate cell seeding by centrifugal casting and increase hydrogel retention, without compromising the biomechanical properties of the scaffold. Micropores with diameters of 50, 100, and 200 mum were machined at different linear densities in decellularized small intestine submucosa (SIS) planar sheets and tubular SIS scaffolds using an argon laser. The ultimate stress and ultimate strain values for SIS sheets with laser-machined micropores with diameter 50 mum and distance between holes as low as 714 mum were not significantly different from unmachined control SIS specimens. Centrifugal casting of GFP-labeled cells suspended in an in situ cross-linkable hyaluronan-based hydrogel resulted in scaffold recellularization with a high density of viable cells inside the laser-machined micropores. Perfusion tests demonstrated the retention of the cells encapsulated within the HA hydrogel in the microholes. Thus, an SIS scaffold with appropriately sized microholes can be loaded with hydrogel encapsulated cells by centrifugal casting to give a mechanically robust construct that retains the cell-seeded hydrogel, permitting rapid biofabrication of tubular tissue construct in a "bioreactor-free" fashion.     

Cell and biomolecule delivery for regenerative medicine

Regenerative medicine is an exciting field that aims to create regenerative alternatives to harvest tissues for transplantation. In this approach, the delivery of cells and biological molecules plays a central role. The scaffold (synthetic temporary extracellular matrix) delivers cells to the regenerative site and provides three-dimensional environments for the cells. To fulfil these functions, we design biodegradable polymer scaffolds with structural features on multiple size scales. To enhance positive cell–material interactions, we design nano-sized structural features in the scaffolds to mimic the natural extracellular matrix. We also integrate micro-sized pore networks to facilitate mass transport and neo tissue regeneration. We also design novel polymer devices and self-assembled nanospheres for biomolecule delivery to recapitulate key events in developmental and wound healing processes. Herein, we present recent work in biomedical polymer synthesis, novel processing techniques, surface engineering and biologic delivery. Examples of enhanced cellular/tissue function and regenerative outcomes of these approaches are discussed to demonstrate the excitement of the biomimetic scaffold design and biologic delivery in regenerative medicine.     

Nanoscale ZnO induces cytotoxicity and DNA damage in human cell lines and rat primary neuronal cells

The toxic effects of ZnO nanoparticles (nano-ZnO) (1-100 microg/mL) suspended in DMEM were examined in human A549 cells, HepG2 cells, human skin fibroblast cells, human skin keratinocytes, and rat primary neuronal cells for 24 h. Nano-ZnO induced dose dependent cytotoxicity and damaged cell membranes. Cell death was not mediated by reactive oxygen species (ROS) or apoptosis. Nano-ZnO induced DNA damage in rat primary neuronal cells, human fibroblasts, and A549 cells. The cytotoxicity of nano-ZnO in DMEM supplemented with 10% FBS, instead of serum free DMEM, was also examined in the A549 cells, human skin fibroblast cells, and human skin keratinocytes. The levels of cytotoxicity induced were similar to those tested without FBS; in addition, ROS was observed. These results indicate that the cause of cytotoxicity is medium dependent and imply that cellular growth conditions may play a significant role in induction of cytotoxicity and DNA damage by nano-ZnO.     

3-D Nanofibrous electrospun multilayered construct is an alternative ECM mimicking scaffold

Extra cellular matrix (ECM) is a natural cell environment, possesses complicated nano- and macro- architecture. Mimicking this three-dimensional (3-D) web is a challenge in the modern tissue engineering. This study examined the application of a novel 3-D construct, produced by multilayered organization of electrospun nanofiber membranes, for human bone marrow-derived mesenchymal stem cells (hMSCs) support. The hMSCs were seeded on an electrospun scaffold composed of poly ε-caproloactone (PCL) and collagen (COL) (1:1), and cultured in a dynamic flow bioreactor prior to in vivo implantation. Cell viability after seeding was analyzed by AlamarBlue™ Assay. At the various stages of experiment, cell morphology was examined by histology, scanning electron microscopy (SEM) and confocal microscopy. Results: A porous 3-D network of randomly oriented nanofibers appeared to support cell attachment in a way similar to traditionally used tissue culture polysterene plate. The following 6 week culture process of the tested construct in the dynamic flow system led to massive cell proliferation with even distribution inside the scaffold. Subcutaneous implantation of the cultured construct into nude mice demonstrated good integration with the surrounding tissues and neovascularization. Conclusion: The combination of electrospinning technology with multilayer technique resulted in the novel 3-D nanofiber multilayered construct, able to contain efficient cell mass necessary for a successful in vivo grafting. The success of this approach with undifferentiated cells implies the possibility of its application as a platform for development of constructs with cells directed into various tissue types.     

Correlation between properties and microstructure of laser sintered porous β-tricalcium phosphate bone scaffolds

Abstract

A porous β-tricalcium phosphate (β-TCP) bioceramic scaffold was successfully prepared with our homemade selective laser sintering system. Microstructure observation by a scanning electron microscope showed that the grains grew from 0.21 to 1.32 μm with the decrease of laser scanning speed from 250 to 50 mm min^?1. The mechanical properties increased mainly due to the improved apparent density when the laser scanning speed decreased to 150 mm min^?1. When the scanning speed was further decreased, the grain size became larger and the mechanical properties severely decreased. The highest Vickers hardness and fracture toughness of the scaffold were 3.59 GPa and 1.16 MPa m^1/2, respectively, when laser power was 11 W, spot size was 1 mm in diameter, layer thickness was 0.1–0.2 mm and laser scanning speed was 150 mm min^?1. The biocompatibility of these scaffolds was assessed in vitro with MG63 osteoblast-like cells and human bone marrow mesenchymal stem cells. The results showed that all the prepared scaffolds are suitable for cell attachment and differentiation. Moreover, the smaller the grain size, the better the cell biocompatibility. The porous scaffold with a grain size of 0.71 μm was immersed in a simulated body fluid for different days to assess the bioactivity. The surface of the scaffold was covered by a bone-like apatite layer, which indicated that the β-TCP scaffold possesses good bioactivity. These discoveries demonstrated the evolution rule between grain microstructure and the properties that give a useful reference for the fabrication of β-TCP bone scaffolds.     

Fabrication of three-dimensional nano, micro and micro/nano scaffolds of porous poly(lactic acid) by electrospinning and comparison of cell infiltration by Z-stacking/three-dimensional projection technique

The use of electrospun extracellular matrix (ECM)-mimicking nanofibrous scaffolds for tissue engineering is limited by poor cellular infiltration. The authors hypothesised that cell penetration could be enhanced in scaffolds by using a hierarchical structure where nano fibres are combined with micron-scale fibres while preserving the overall scaffold architecture. To assess this, we fabricated electrospun porous poly(lactic acid) (PLA) scaffolds having nanoscale, microscale and combined micro/nano architecture and evaluated the structural characteristics and biological response in detail. Although the bioactivity was intermediate to that for nanofibre and microfibre scaffold, a unique result of this study was that the micro/nano combined fibrous scaffold showed improved cell infiltration and distribution than the nanofibrous scaffold. Although the cells were found to be lining the scaffold periphery in the case of nanofibrous scaffold, micro/nano scaffolds had cells dispersed throughout the scaffold. Further, as expected, the addition of nanoparticles of hydroxyapatite (nHAp) improved the bioactivity, although it did not play a significant role in cell penetration. Thus, this strategy of creating a three-dimensional (3D) micro/nano architecture that would increase the porosity of the fibrous scaffold and thereby improving the cell penetration, can be utilised for the generation of functional tissue engineered constructs in vitro.     

Atorvastatin lipid nanocapsules and gold nanoparticles embedded in injectable thermo‐gelling hydrogel scaffold containing adipose tissue extracellular matrix for myocardial tissue regeneration

This study aimed to prepare, optimise, and characterise the novel hybrid hydrogel scaffold containing atorvastatin lipid nanocapsules (LNCs) and gold nanoparticles (NPs) to improve cardiomyoblasts proliferation and regeneration of myocardium. A thermo‐responsive aminated guaran (AGG) hydrogel was prepared to encompass extracellular matrix (ECM) fetched from human adipose tissue. Emulsion phase‐inversion technique was used to obtain LNCs. Biocompatibility, tensile strength, conductivity, and proliferation of human myocardial cells of the optimised formulation were studied. The LNCs have a spherical shape, and the optimised formulation showed a mean particle size of 18.79 nm, the zeta potential of − 11.4 mV, drug loading of 99.99%, and release efficiency percent over 72 h was 18.73%. The injectable thermo‐sensitive hydrogel prepared using 1 w/v% of AGG, 35 w/w% of ECM, ∼0.5 mg/ml of gold NPs and atorvastatin loaded LNCs showed the best physical characteristics. The hybrid scaffold loaded with atorvastatin and gold NPs improved the proliferation of cardiomyoblasts more than sevenfold with enhanced cell attachment to the scaffold. The tensile strength and the conductivity of the scaffold were 300 kPa and 0.14 S/m, respectively. Injectable hybrid adipose tissue prepared by ECM and AGG hydrogel loaded with atorvastatin and gold NPs showed promising physical characteristics for myocardial tissue engineering.Inspec keywords: biological tissues, nanoparticles, tensile strength, electrokinetic effects, particle size, nanomedicine, emulsions, biomedical materials, cellular biophysics, nanofabrication, drugs, drug delivery systems, molecular biophysics, tissue engineering, hydrogels, goldOther keywords: Au, cardiomyoblast, hybrid hydrogel scaffold, myocardial tissue engineering, AGG hydrogel, injectable hybrid adipose tissue, atorvastatin loaded LNCs, gold NPs, thermo‐sensitive hydrogel, drug loading, human myocardial cells, tensile strength, emulsion phase‐inversion technique, human adipose tissue, ECM, thermo‐responsive aminated guaran hydrogel, cardiomyoblasts proliferation, atorvastatin lipid nanocapsules, myocardial tissue regeneration, adipose tissue extracellular matrix, thermo‐gelling hydrogel scaffold, gold nanoparticles     

Characterization of and host response to tyramine substituted-hyaluronan enriched fascia extracellular matrix

Naturally-occurring biomaterial scaffolds derived from extracellular matrix (ECM) have been previously investigated for soft tissue repair. We propose to enrich fascia ECM with high molecular weight tyramine substituted-hyaluronan (TS-HA) to modulate inflammation associated with implantation and enhance fibroblast infiltration. As critical determinants of constructive remodeling, the host inflammatory response and macrophage polarization to TS-HA enriched fascia were characterized in a rat abdominal wall model. TS-HA treated fascia with cross-linking had a similar lymphocyte (P = 0.11) and plasma cell (P = 0.13) densities, greater macrophage (P = 0.001) and giant cell (P < 0.0001) densities, and a lower density of fibroblast-like cells (P < 0.0001) than water treated controls. Treated fascia, with or without cross-linking, exhibited a predominantly M2 pro-remodeling macrophage profile similar to water controls (P = 0.82), which is suggestive of constructive tissue remodeling. Our findings demonstrated that HA augmentation can alter the host response to an ECM, but the appropriate concentration and molecular weight needed to minimize chronic inflammation within the scaffold remains to be determined.