Induction of EPC homing on biofunctionalized vascular grafts for rapid in vivo self-endothelialization — A review of current strategies

For years intensive research has been done to improve the hemocompatibility of blood contacting vascular devices. Despite the enormous progress in physicochemical surface optimization technologies, the native endothelium still represents the ideal surface for blood contact. Numerous tissue engineering strategies aspired towards the endothelialization of graft surfaces to generate a non-thrombogenic barrier on artificial materials. A paradigm change in surface modification concepts is the in vivo endothelialization of vascular grafts by capturing circulating endothelial progenitor cells (EPCs) directly from the blood stream via biofunctionalized implant materials. Thereby, capture molecules are immobilized on artificial vascular grafts to mimic a pro-homing substrate for EPCs. In this review, different coating strategies for in vivo capturing of EPCs on synthetic implants are discussed. This therapeutic concept opens a new chapter in regenerative medicine by realizing the vision that every patient seeds his implants with his own progenitor cells to make the synthetic grafts unrecognizable for the body's rejection mechanisms.     

Subfascial breast implant: a new procedure

Breast augmentation techniques using the submuscular and subglandular planes to introduce the implant are well known and widely used procedures. The authors have been using the subfascial dissection plane, a new concept for breast augmentation. From October of 1998 to September of 2001, 263 patients underwent breast augmentation. In all cases, the implants were inserted into the subfascial plane. McGhan 410 anatomic biodimensional, cohesive gel implants (size, 155 to 310 g) were used. There are additional benefits using this technique; these include avoiding implant deformation or distortion (as seen in the retromuscular position), leaving additional soft tissue between the implant and the skin, and minimizing implant edge prominence (inherent to retroglandular placement). These technical details lead to fewer patient complaints. Morbidity is similar to that of other techniques.     

Soft and hard tissue response to zirconium dioxide dental implants--a clinical study in man

Titanium dental implants have been used successfully in implantology for more than 40 years. Recent research, however, suggests that titanium might have more side effects than previously believed. Zirconia ceramics have been employed in orthopaedic surgery for approximately 30 years and were recently introduced into dentistry as a metal replacement for crown and bridge work as well as implant abutments. Zirconium dioxide has been shown in both in vitro and in vivo studies to have desirable osseointegrative properties. This clinical study shows that dental implants made from zirconia are a feasible alternative to titanium dental implants. In addition to excellent cosmetic results, zirconia implants allow a degree of osseointegration and soft tissue response that is superior to titanium dental implants.     

Radiolucent prosthetic gel.

The successful use of silicone breast implants is complicated by their interference with mammography. We have evaluated clinically available implant filling materials and found that a new Bio-Oncotic gel approximates the radiolucency of normal breast tissue. Silicone implants completely obscure areas of the breast in mammography. Recently proposed as a filler material, peanut oil is significantly more radiolucent than normal tissue. Physiologic saline solution compares favorably as a tissue-density-simulating substance. However, saline's lack of lubricating properties results in leakage, making it less than optimal. Bio-Oncotic gel is biologically compatible. We conclude that this gel is the most appropriate filler for breast prostheses. Clinical studies are indicated.     

Breast augmentation: choosing the optimal incision, implant, and pocket plane

A retrospective study of 220 patients was performed to review surgical design in breast augmentation. Three specific issues were studied: incision site, implant variables, and pocket plane selection. The influence of these three factors on aesthetic results in both primary and secondary cases was the focus of the analysis. No attempt was made to address long-term issues such as capsular contracture or saline implant deflation rates. In 77 primary augmentation patients and 80 unilateral augmentations for symmetry in breast reconstruction, there were the following untoward results: 11 revisions for unilateral malposition, change to a different implant shape, or change to a larger implant size; four deflations of saline implants requiring replacement; and four conversions of saline to silicone gel implants. In 63 secondary cases, there were two hematomas and two infections requiring implant removal and subsequent replacement. Operative technique in breast augmentation is described, as are recommendations for each of the options associated with the three variables studied.     

Intracapsular allogenic dermal grafts for breast implant-related problems

Despite advances in surgical techniques and breast implant design, certain problems unique to breast implant surgery remain. The historically most onerous problem, capsular contracture, is relatively uncommon now. However, problems related to thin capsules and periprosthetic atrophy are becoming more common; these problems include rippling, symmastia, implant malposition, and bottoming out. Options for treatment of these conditions remain extremely limited, particularly with saline implants. Allogenic dermal grafting provides one satisfactory option. Techniques for use of allogenic dermal grafts and early results from 10 patients are summarized in this article, along with histologic analysis confirming viability of the grafts at 6-month follow-up in one patient. No graft-related complications were identified.     

Comparison of the biological activities of high-density porous polyethylene implants and oxidized regenerated cellulose-wrapped diced cartilage grafts

The use of alloplastic materials in plastic surgery has become more extensive with advancement of autogenous-tissue reconstruction techniques for the repair of defects, tissue augmentation, and the stabilization of bones. An ideal alloplastic material should be nonallergenic, noncarcinogenic, sterilizable, and easy to shape and should not cause rejection. Alloplastic material used for tissue augmentation should have a low rate of resorption and distortion. High-density porous polyethylene implants (Medpor) have been used widely and successfully for tissue augmentation. The Turkish Delight is a material composed of diced cartilage grafts wrapped in oxidized regenerated cellulose (Surgicel). Its indications are similar to those of the Medpor implant, and an additional donor site is usually not needed. Both materials are used in the same anatomical locations, especially for augmentation. Therefore, the authors evaluated the long-term stability of and suitable anatomical sites for these materials. Medpor implants or Turkish Delights were placed subperiosteally or subfascially in 10 young rabbits, and the resultant changes were evaluated 16 weeks after the operation by macroscopy and histopathology. Changes in projections were measured with an ocular micrometer. Medpor implants were neither resorbed nor distorted when placed subperiosteally or subfascially, and were highly stabilized by the surrounding tissues. Turkish Delight also enabled tissue augmentation, but had a significantly higher rate of resorption compared with the Medpor implant and was loosely bound to the surrounding tissue. The Turkish Delight was less resorbed and better fixed to adjacent tissues when placed subperiosteally than when placed subfascially.     

Textured-surface saline-filled silicone breast implants for augmentation mammaplasty

The earliest silicone breast implants were smooth-surface, silicone rubber devices filled with either silicone gel or saline. Because of persistent problems with capsular contracture, polyurethane-covered silicone implants were developed as an alternative. Particularly in the short run, these alternatives proved highly successful at reducing the incidence of capsular contracture. By 1990, polyurethane-covered implants were rapidly becoming the preferred implant choice of many plastic surgeons, but for legal, regulatory, financial, and safety reasons they were withdrawn from the market by Bristol-Myers in 1991. Meanwhile, during the late 1980s, surface texturing and improved materials became available on other silicone breast implants and expanders. Most studies suggest that textured-surface silicone gel-filled implants, saline-filled implants, and tissue expanders have less frequent capsular contracture than their smooth-surface counterparts.     

Analysis of risk factors associated with rupture of silicone gel breast implants

Despite many recent studies on breast implant rupture, there is no general consensus on causation or incidence. Existing studies have not reported a multivariate analysis of risk factors associated with breast implant rupture. Most studies lack adequate sample size to study the effect of implant type, manufacturer, and other patient-related factors that might affect rupture. This study addresses all of these shortcomings. Patients undergoing implant removal by a single surgeon between 1990 and 1996 were examined for rupture and for 16 potential risk factors. The association between rupture and various factors was analyzed by univariate and multivariate analyses. A total of 842 patients underwent removal of 1619 implants. Increasing age of implant [p < 0.0001; adjusted odds ratio (OR), 1.20; 95% confidence interval (CI), 1.15 to 1.23], retroglandular location (p = 0.0002; OR, 1.93; CI, 1.37 to 2.71), Baker contracture grades III and IV (p = 0.005; OR, 1.52; CI, 1.14 to 2.03), and presence of local symptoms (p = 0.05; OR, 1.37; CI, 1.00 to 1.89) were associated with rupture. When different implant types were compared with smooth gel implants, after adjustment, double-lumen (p < 0.0001; OR, 0.33; CI, 0.22 to 0.50) and polyurethane-covered implants (p < 0.0002; OR, 0.33; CI, 0.20 to 0.57) had significantly lower rupture rates. When various manufacturers were compared with Dow Corning after adjusting for other factors, rupture rates were significantly lower for McGhan (p < 0.0001; OR, 0.41; CI, 0.26 to 0.65), whereas higher for Surgitek (p < 0.019; OR, 1.52; CI, 1.05 to 2.18). Significant risk factors for breast implant rupture were identified: older implants, retroglandular implant location, implant contracture, local symptoms, certain implant type, and certain manufacturer. Although the results of this study are based on a nonrandomized explant population from a single surgeon's practice, knowledge of these risk factors will permit better interpretation of future data on rupture. The knowledge will enable the medical community to better advise their breast implant population regarding durability and appropriate time for removal or replacement.     

Self-reported diseases and symptoms by rupture status among unselected Danish women with cosmetic silicone breast implants

Epidemiologic evidence does not support an association between silicone breast implants and connective tissue or other rheumatic diseases. However, a recent study has suggested that women with ruptured implants may be at increased risk of developing fibromyalgia. An analysis of adverse health outcomes according to breast implant rupture status was conducted in 238 unselected Danish women with cosmetic silicone breast implants. Ninety-two of the women had definite implant rupture, and 146 had intact implants as determined by magnetic resonance imaging. Before undergoing imaging, the women provided blood samples and completed a self-administered questionnaire. Women with ruptured implants overall, and the subgroup with extracapsular ruptures (n = 23), were compared with women with intact implants regarding a number of self-reported diseases and symptoms and the presence of specific autoantibodies, such as antinuclear antibodies, rheumatoid factor, and cardiolipin immunoglobulin G and M antibodies. Overall, there were no differences in the occurrence of self-reported diseases or symptoms or in the presence of autoantibodies between women with intact implants and women with ruptured implants, including extracapsular rupture. The only exception was capsular contracture, which was reported six times more frequently by women with extracapsular ruptures than by women with intact implants (OR, 6.3; 95 percent CI, 1.7 to 23.5). In conclusion, this study of unselected women with silicone breast implants could establish no association between silicone implant rupture and specific diseases or symptoms related to connective tissue disease or other rheumatic conditions, except for an excess of capsular contracture among women with extracapsular rupture.     

Vascular remodeling and angiogenesis in ectopic ovarian transplants: a crucial role of pericytes and vascular smooth muscle cells in maintenance of ovarian grafts

Cancer patients, treated by either chemo- or radiotherapy, frequently suffer from ovarian failure and infertility. One of the new emerging techniques to preserve reproductive potential of such patients is cryopreservation of ovarian fragments prior to treatment and their retransplantation after healing. A major obstacle in survival of the ovarian implants is vascular failure, which leads to tissue necrosis. In order to investigate the role of angiogenesis in implant preservation, we used a xenograft model in which rat ovaries were transplanted into immunodeficient mice. Graft reception and maintenance were monitored by magnetic resonance imaging (MRI) and histology. Two transplantation sites were explored, i.e., subcutaneous and intramuscular. Comparison between these two transplantation sites revealed the importance of vascular smooth muscle cells and pericytes in sustaining vascular and tissue integrity. Histological examination of the grafts, at different time points and sizes, revealed that loss of perivascular cells preceded damage to endothelial cells and was closely correlated with loss of follicular and oocyte integrity. Intramuscular implantation provided better maintenance of implant perivascular cells relative to subcutaneous implantation. Accordingly, follicular integrity was superior in the intramuscular implants and the number of damaged follicles was significantly lower compared with the subcutaneous transplantation site. These results suggest that improving ovarian implant maintenance should be directed toward preservation of perivascular support.     

Variability in the properties of silicone gel breast implants.

Several generations of silicone gel breast implants have been produced by implant manufacturers. The primary material usually viewed as the base material in the manufacture of implants is polydimethylsiloxane. Polymeric reactions are notorious for their variability and nonuniformity. The elastomer used in different types of implants can have vastly different properties. Furthermore, the material properties associated with a particular type of implant can vary considerably from one lot to the next. Considering the various designs, styles, and manufacturing techniques associated with silicone gel implants, knowledge of the original properties of the implants before implantation is important in determining the effects of aging in vivo. This study was conducted to investigate differences in key mechanical and chemical properties of silicone gel breast implant materials. The two types of implants chosen for analysis were Silastic I and Silastic II control implants. Material property data were determined for both types of controls and significant differences were found in their values. Lot-to-lot variability was also investigated and found to be significant.     

Surgical treatment of breast cancer in previously augmented patients

The incidence of breast cancer is increasing each year. Concomitantly, cosmetic breast augmentation has become the second most often performed cosmetic surgical procedure. As the augmented patient population ages, an increasing number of breast cancer cases among previously augmented women can be anticipated. The surgical treatment of these patients is controversial, with several questions remaining unanswered. Is breast conservation therapy feasible in this patient population and can these patients retain their implants? A retrospective review of all breast cancer patients with a history of previous augmentation mammaplasty who were treated at the Revlon/UCLA Breast Center between 1991 and 2001 was performed. During the study period, 58 patients were treated. Thirty patients (52 percent) were treated with a modified radical mastectomy with implant removal. Twenty-eight patients (48 percent) underwent breast conservation therapy, which consisted of lumpectomy, axillary lymph node dissection, and radiotherapy. Twenty-two of the patients who underwent breast conservation therapy initially retained their implants. Eleven of those 22 patients (50 percent) ultimately required completion mastectomies with implant removal because of implant complications (two patients), local recurrences (five patients), or the inability to obtain negative margins (four patients). Nine additional patients experienced complications resulting from their implants, including contracture, erosion, pain, and rupture. The data illustrate that breast conservation therapy with maintenance of the implant is not ideal for the majority of augmented patients. Breast conservation therapy with explantation and mastopexy might be appropriate for rare patients with large volumes of native breast tissue. Mastectomy with immediate reconstruction might be a more suitable choice for these patients.     

Breast reconstruction using tissue expanders and implants in Hodgkin's patients with prior mantle irradiation.

Women treated for Hodgkin's disease with mantle irradiation have an increased risk for developing breast cancer. Typically, breast malignancy in Hodgkin's patients presents bilaterally in a younger age group. Skin flap ischemia, poor skin expansion, implant extrusion, capsular contracture, and poor cosmesis are common sequelae of tissue expander/implant breast reconstruction after breast irradiation for failed breast conservation therapy. This has led most surgeons to favor autologous tissue reconstruction in this setting. This study was performed to determine the efficacy of tissue expander/implant breast reconstruction in breast cancer patients who have been treated with prior mantle irradiation for Hodgkin's disease. A retrospective analysis of all breast cancer patients with a history of Hodgkin's disease and mantle irradiation treated with mastectomy and tissue expander/implant reconstruction between 1992 and 1999 was performed. There were seven patients, with a mean age of 35 years (range, 28 to 42 years). The average interval between mantle irradiation and breast cancer diagnosis was 16 years (range, 12 to 23 years). All patients underwent two-stage reconstruction. Textured surface tissue expanders were placed in a complete submuscular position at the time of mastectomy. Expansion was initiated 2 weeks after insertion and continued on a weekly basis until completion. Expanders were replaced with textured surface saline-filled implants as a second stage. Patients were evaluated for skin flap ischemia, infection, quality of skin expansion, implant extrusion, capsular contracture, rippling, symmetry, and final aesthetic outcome. Breast cancer was bilateral in five patients and unilateral in two. Two patients did not undergo simultaneous bilateral breast reconstruction because of metachronous cancer development. One of the patients had an initial transverse rectus abdominis muscle flap breast reconstruction, followed by a tissue expander/implant reconstruction of the opposite breast. The average follow-up was 3 years. Complications were limited to one case of cellulitis after implant placement that resolved with intravenous antibiotics. There were no cases of skin flap ischemia, poor skin expansion, or implant extrusion. Overall patient satisfaction was high and revisions were not requested or required. Symmetry was best achieved with bilateral implants. This study demonstrates the efficacy of tissue expander/implant breast reconstruction in patients treated with prior mantle irradiation. In this series, tissue expansion was reliable with low morbidity. Second-stage placement of permanent implants yielded good aesthetic results without significant capsular contracture. Mantle irradiation did not appear to compromise the prosthetic breast reconstruction. Tissue expander/implant breast reconstruction should remain a viable option in this category of irradiated patients.     

Options to avoid the second surgical site: a review of literature

As esthetics gain importance, periodontal plastic surgical procedures involving soft tissue grafts are becoming commoner both around natural teeth as well as around implants. Periodontal soft tissue grafts are primarily used for the purpose of root coverage and in pre-prosthetic surgery to thicken a gingival site or to improve the crestal volume. Soft tissue grafts are usually harvested from the palate. Periodontal plastic surgical procedures involving soft tissue grafts harvested from the palate have two surgical sites; a recipient site and another donor site. Many patients are apprehensive about the soft tissue graft procedures, especially the creation of the second/donor surgical site in the palate. In the past decade, newer techniques and products have emerged which provide an option for the periodontist/patient to avoid the second surgical site. MucoMatrixX, Alloderm^®, Platelet rich fibrin, Puros^® Dermis and Mucograft^® are the various options available to the practicing periodontist to avoid the second surgical site. Use of these soft tissue allografts in an apprehensive patient would decrease patient morbidity and increase patient’s acceptance towards periodontal plastic surgical procedures.     

A combined strategy to reduce restenosis for vascular tissue engineering applications

Biodegradable polymers including poly(l-lactic acid) (PLLA) have been used to develop cardiovascular prostheses such as vascular grafts and stents. However, implant-associated thrombosis, inflammation, and restenosis are still major obstacles for the utility of these devices. The lack of an endothelial cell (EC) lining (endothelialization) on the implants and the responses of the immune systems toward the implants have been associated with these complications. In our research strategy, we have combined the drug delivery principle with the strategies of tissue engineering, the controlled release of anti-inflammation drugs and enhanced endothelialization, to reduce the implant-associated adverse responses. We first integrated curcumin, an anti-inflammatory drug and anti-smooth muscle cell (SMC) proliferative drug, with PLLA. This curcumin-loaded PLLA material was then modified using adsorptive coating of adhesive proteins such as fibronectin, collagen-I, vitronectin, laminin, and matrigel to improve the endothelial cell (EC) adhesion and proliferation, and ECs were seeded on top of these modified surfaces. Our results showed steady drug release kinetics over the period of 50 days from curcumin-loaded PLLA materials. Additionally, integration of curcumin in PLLA increased the roughness of the scaffold at the nanometric scale using an atomic force microscopic analysis. Moreover, coating with fibronectin on curcumin-loaded PLLA surfaces gave the highest EC adhesion and proliferation compared to other adhesive proteins using PicoGreen DNA assays. The ability of our strategy to release the curcumin for producing anti-inflammation and anti-proliferation responses and to improve EC adhesion and growth after EC seeding suggests this strategy may reduce implant-associated adverse responses and be a better approach for vascular tissue engineering applications.     

Experimental hydroxyapatite cement cranioplasty.

Hydroxyapatite cement is a calcium phosphate-based material that when mixed with water forms a dense paste that sets within 15 minutes and isothermically converts in vivo to a microporous hydroxyapatite implant. This cement was used to reconstruct bilateral 2.5-cm-diameter full-thickness critical-sized parietal skull defects in six cats. One side was reconstructed with 100 percent hydroxyapatite cement, and the other with a mixture of 50 percent hydroxyapatite cement and 50 percent ground autogenous bone by weight. These animals were sacrificed at 6 and 12 months after implantation. Positive and negative controls also were prepared. The anatomic contour of the soft tissue overlying all hydroxyapatite cement implants was well maintained, there were no wound infections or structural failures, and the implants were well tolerated histologically. None of the negative (unreconstructed) control defects was completely filled with repair bone, and all positive (methyl methacrylate) controls demonstrated foreign-body giant-cell formation and fibrous encapsulation of the implants. Examination of decalcified and undecalcified sections revealed progressive but variable replacement of the cement by new bone and soft tissue without a change in the shape or volume of the hydroxyapatite cement-reconstructed areas. New bone comprised 77.3 and 64.7 percent of the tissue replacing the hydroxyapatite cement and hydroxyapatite cement-bone implants, respectively. Replacement of the hydroxyapatite cement implants by new bone is postulated to occur by a combination of osteoconduction and implant resorption. These results indicate that further experimental research leading to the possible application of hydroxyapatite cement for full-thickness calvarial defect reconstruction in humans is warranted.     

Staged breast reconstruction with saline-filled implants in the irradiated breast: recent trends and therapeutic implications

A retrospective review was performed of one surgeon's experience with 40 consecutive patients who had undergone two-stage saline-filled implant breast reconstruction and radiation during the period from 1990 through 1997. A randomly selected group of 40 other two-stage saline-filled implant breast reconstructions from the same surgeon and time period served as controls. This review was undertaken because of the absence of specific information on the outcome of staged saline implant reconstructions in the radiated breast. Previously published reports on silicone gel implants and radiation have been contradictory. At the same time, the criteria for the use of radiation in the treatment of breast cancer have been expanded and the numbers of reconstruction patients who have been radiated are increasing dramatically. For example, in a 1985 report on immediate breast reconstruction, only 1 of 185 patients over a 6-year period underwent adjuvant radiation therapy, whereas in this review, there were 40 radiated breasts with saline-filled implants, 19 of which received adjuvant radiation therapy during their expansion. The study parameters included patient age, breast cup size, implant size, length of follow-up, number of procedures, coincident flap operations, Baker classification, complications, opposite breast procedures, pathologic stage, indications for and details about the radiation, and outcomes. The use of radiation in this review of reconstructed breasts can logically be divided into four groups: previous lumpectomy and radiation (n = 7), mastectomy and radiation before reconstruction (n = 9), mastectomy and adjuvant radiation during reconstruction/expansion (n = 19), and radiation after reconstruction (n = 5). The largest and most rapidly growing group of patients is of those receiving postmastectomy adjuvant radiation therapy. A total of 47.5 percent (19 of 40) of radiated breasts with saline implants ultimately needed the addition of, or replacement by, a flap. Ten percent of a control group with nonradiated saline implant reconstructions also had flaps, none as replacements. Fifty percent or more of both the radiated and control groups had contralateral surgery. Complications were far more common in the radiated group; for example, there were 32.5 percent capsular contractures compared with none in the control group. The control nonradiated implant-only group and the flap plus implant radiated group did well cosmetically. The radiated implant-only group was judged the worst. The increasing use of radiation after mastectomy has important implications for breast reconstruction. The possibility for radiation should be thoroughly investigated and anticipated preoperatively before immediate breast reconstruction. Patients with invasive disease, particularly with large tumors or palpable axillary lymph nodes, are especially likely to be encouraged to undergo postmastectomy radiation therapy. The indications for adjuvant radiation therapy have included four or more positive axillary lymph nodes, tumors 4 cm (or more) in diameter, and tumors at or near the margin of resection. More recently, some centers are recommending adjuvant radiation therapy for patients with as few as one positive lymph node or even in situ carcinoma close to the resection margin. The use of latissimus dorsi flaps after radiation has proven to be an excellent solution to postradiation tissue contracture, which can occur during breast expander reconstruction. The use of the latissimus flap electively with skin-sparing mastectomy preradiation is probably unwise, unless postmastectomy radiation is unlikely. Skin-sparing mastectomy with a latissimus flap thus should be preserved for patients unlikely to undergo adjuvant radiation therapy. Purely autologous reconstruction such as a TRAM flap is another option for these patients, either before or after radiation therapy.     

Nanotopographical control of human osteoprogenitor differentiation

Current load-bearing orthopaedic implants are produced in 'bio-inert' materials such as titanium alloys. When inserted into the reamed bone during hip or knee replacement surgery the implants interact with mesenchymal populations including the bone marrow. Bio-inert materials are shielded from the body by differentiation of the cells along the fibroblastic lineage producing scar tissue and inferior healing. This is exacerbated by implant micromotion, which can lead to capsule formation. Thus, next-generation implant materials will have to elicit influence over osteoprogenitor differentiation and mesenchymal populations in order to recruit osteoblastic cells and produce direct bone apposition onto the implant. A powerful method of delivering cues to cells is via topography. Micro-scale topography has been shown to affect cell adhesion, migration, cytoskeleton, proliferation and differentiation of a large range of cell types (thus far all cell types tested have been shown to be responsive to topographical cues). More recent research with nanotopography has also shown a broad range of cell response, with fibroblastic cells sensing down to 10 nm in height. Initial studies with human mesenchymal populations and osteoprogenitor populations have again shown strong cell responses to nanofeatures with increased levels of osteocalcin and osteopontin production from the cells on certain topographies. This is indicative of increased osteoblastic activity on the nanotextured materials. Looking at preliminary data, it is tempting to speculate that progenitor cells are, in fact, more responsive to topography than more mature cell types and that they are actively seeking cues from their environment. This review will investigate the range of nanotopographies available to researchers and our present understanding of mechanisms of progenitor cell response. Finally, it will make some speculations of the future of nanomaterials and progenitor cells in tissue engineering.