Mark S. Lesney

Immediate and continued life-sustaining improvement was seen in three pediatric patients implanted with 3-D–printed tracheobronchial splints as a treatment for terminal tracheobronchomalacia (TBM), a condition of excessive collapse of the airways during respiration leading to cardiopulmonary arrest.

The particular value of such 3-D–printable biomaterials to pediatric surgery is their ability to adopt a 4-D modality – to exhibit specifically engineered shape changes in response to surrounding tissue growth over a defined time period. In addition to their malleability, these devices also are designed to biodegrade. These features have proven especially useful as seen in this medical device emergency use exemption study performed at the University of Michigan, according to a report published in Science Translational Medicine (2015 Apr 29. [doi: 10.1126/scitranslmed.3010825]).

“Our multidisciplinary team designed an archetype device to allow radial expansion of the affected airway over the critical growth period while resisting external compression and intrinsic collapse,” wrote Dr. Robert J. Morrison of the University of Michigan, Ann Arbor, and his colleagues.

The study population involved three infant boys, aged 3 months, 5 months, and 16 months at time of treatment. In each patient, a sternotomy exposed their affected airways. The 3-D–printed splint, consisting of conjoined rib-like C-shaped arches was placed around the affected airway and secured with polypropylene sutures. The splint counters external pressure on the airway and holds it open. Because the splint is malleable, with an expandable opening placed opposite to the main collapsing pressure, it is capable of expanding as the airway grows.

Examination of the airway immediately after placement demonstrated patency, which was confirmed 1 month later. Results showed the benefit of the splints for all three patients, although total results were complicated by additional comorbidities:

• Patient 1: Blood gases returned to normal immediately after implantation and remained normal at 3 months’ follow-up. A week after implantation, weaning from mechanical ventilation was initiated and, 3 weeks after the procedure, the child was discharged to home. Repeat imaging at 1, 3, 6, 12, and 39 months postoperatively demonstrated continued resolution of the TBM, with evidence of fragmentation and degradation of the splint at 39 months.

• Patient 2: Immediately after implantation of the device, blood gases improved greatly and the left lung perfused. The patient had opioid and benzodiazepine dependence from long-term ventilator support, requiring a longer controlled wean from the ventilator. Four weeks after surgery, the patient was transitioned to a portable ventilator system, completely weaned at 15 weeks, and discharged from the hospital to home for the first time in his life.

• Patient 3: After implantation, the patient ceased experiencing life-threatening desaturation episodes and showed sustained improvement in blood gases. Imaging showed continued patency of the left main bronchus with resolution of left-lung air trapping. However, at 14 months post implantation, he remained on permanent ventilator support, “presumably because of distal left segmental bronchomalacia beyond what the splint was designed to address,” according to Dr. Morrison and his colleagues.

“We report successful implantation of patient-specific bioresorbable airway splints for the treatment of severe TBM. The personalized splints conformed to the patients’ individual geometries and expanded with airway growth (in the ‘fourth dimension’),” the researchers summarized.

“The three pediatric patients implanted with these 3-D–printed airway splints had a terminal form of TBM. The clinical improvement in each case was immediate and sustained, suggesting that improvement is not attributable to the natural history of the disease alone,” they concluded.

The study was funded by the National Institutes of Health. Two of the study authors were coinventors of the device for which they have filed a patent. There were no other disclosures.

[email protected]

Immediate and continued life-sustaining improvement was seen in three pediatric patients implanted with 3-D–printed tracheobronchial splints as a treatment for terminal tracheobronchomalacia (TBM), a condition of excessive collapse of the airways during respiration leading to cardiopulmonary arrest.

The particular value of such 3-D–printable biomaterials to pediatric surgery is their ability to adopt a 4-D modality – to exhibit specifically engineered shape changes in response to surrounding tissue growth over a defined time period. In addition to their malleability, these devices also are designed to biodegrade. These features have proven especially useful as seen in this medical device emergency use exemption study performed at the University of Michigan, according to a report published in Science Translational Medicine (2015 Apr 29. [doi: 10.1126/scitranslmed.3010825]).

“Our multidisciplinary team designed an archetype device to allow radial expansion of the affected airway over the critical growth period while resisting external compression and intrinsic collapse,” wrote Dr. Robert J. Morrison of the University of Michigan, Ann Arbor, and his colleagues.

The study population involved three infant boys, aged 3 months, 5 months, and 16 months at time of treatment. In each patient, a sternotomy exposed their affected airways. The 3-D–printed splint, consisting of conjoined rib-like C-shaped arches was placed around the affected airway and secured with polypropylene sutures. The splint counters external pressure on the airway and holds it open. Because the splint is malleable, with an expandable opening placed opposite to the main collapsing pressure, it is capable of expanding as the airway grows.

Examination of the airway immediately after placement demonstrated patency, which was confirmed 1 month later. Results showed the benefit of the splints for all three patients, although total results were complicated by additional comorbidities:

• Patient 1: Blood gases returned to normal immediately after implantation and remained normal at 3 months’ follow-up. A week after implantation, weaning from mechanical ventilation was initiated and, 3 weeks after the procedure, the child was discharged to home. Repeat imaging at 1, 3, 6, 12, and 39 months postoperatively demonstrated continued resolution of the TBM, with evidence of fragmentation and degradation of the splint at 39 months.

• Patient 2: Immediately after implantation of the device, blood gases improved greatly and the left lung perfused. The patient had opioid and benzodiazepine dependence from long-term ventilator support, requiring a longer controlled wean from the ventilator. Four weeks after surgery, the patient was transitioned to a portable ventilator system, completely weaned at 15 weeks, and discharged from the hospital to home for the first time in his life.

• Patient 3: After implantation, the patient ceased experiencing life-threatening desaturation episodes and showed sustained improvement in blood gases. Imaging showed continued patency of the left main bronchus with resolution of left-lung air trapping. However, at 14 months post implantation, he remained on permanent ventilator support, “presumably because of distal left segmental bronchomalacia beyond what the splint was designed to address,” according to Dr. Morrison and his colleagues.

“We report successful implantation of patient-specific bioresorbable airway splints for the treatment of severe TBM. The personalized splints conformed to the patients’ individual geometries and expanded with airway growth (in the ‘fourth dimension’),” the researchers summarized.

“The three pediatric patients implanted with these 3-D–printed airway splints had a terminal form of TBM. The clinical improvement in each case was immediate and sustained, suggesting that improvement is not attributable to the natural history of the disease alone,” they concluded.

The study was funded by the National Institutes of Health. Two of the study authors were coinventors of the device for which they have filed a patent. There were no other disclosures.

[email protected]

Immediate and continued life-sustaining improvement was seen in three pediatric patients implanted with 3-D–printed tracheobronchial splints as a treatment for terminal tracheobronchomalacia (TBM), a condition of excessive collapse of the airways during respiration leading to cardiopulmonary arrest.

The particular value of such 3-D–printable biomaterials to pediatric surgery is their ability to adopt a 4-D modality – to exhibit specifically engineered shape changes in response to surrounding tissue growth over a defined time period. In addition to their malleability, these devices also are designed to biodegrade. These features have proven especially useful as seen in this medical device emergency use exemption study performed at the University of Michigan, according to a report published in Science Translational Medicine (2015 Apr 29. [doi: 10.1126/scitranslmed.3010825]).

“Our multidisciplinary team designed an archetype device to allow radial expansion of the affected airway over the critical growth period while resisting external compression and intrinsic collapse,” wrote Dr. Robert J. Morrison of the University of Michigan, Ann Arbor, and his colleagues.

The study population involved three infant boys, aged 3 months, 5 months, and 16 months at time of treatment. In each patient, a sternotomy exposed their affected airways. The 3-D–printed splint, consisting of conjoined rib-like C-shaped arches was placed around the affected airway and secured with polypropylene sutures. The splint counters external pressure on the airway and holds it open. Because the splint is malleable, with an expandable opening placed opposite to the main collapsing pressure, it is capable of expanding as the airway grows.

Examination of the airway immediately after placement demonstrated patency, which was confirmed 1 month later. Results showed the benefit of the splints for all three patients, although total results were complicated by additional comorbidities:

• Patient 1: Blood gases returned to normal immediately after implantation and remained normal at 3 months’ follow-up. A week after implantation, weaning from mechanical ventilation was initiated and, 3 weeks after the procedure, the child was discharged to home. Repeat imaging at 1, 3, 6, 12, and 39 months postoperatively demonstrated continued resolution of the TBM, with evidence of fragmentation and degradation of the splint at 39 months.

• Patient 2: Immediately after implantation of the device, blood gases improved greatly and the left lung perfused. The patient had opioid and benzodiazepine dependence from long-term ventilator support, requiring a longer controlled wean from the ventilator. Four weeks after surgery, the patient was transitioned to a portable ventilator system, completely weaned at 15 weeks, and discharged from the hospital to home for the first time in his life.

• Patient 3: After implantation, the patient ceased experiencing life-threatening desaturation episodes and showed sustained improvement in blood gases. Imaging showed continued patency of the left main bronchus with resolution of left-lung air trapping. However, at 14 months post implantation, he remained on permanent ventilator support, “presumably because of distal left segmental bronchomalacia beyond what the splint was designed to address,” according to Dr. Morrison and his colleagues.

“We report successful implantation of patient-specific bioresorbable airway splints for the treatment of severe TBM. The personalized splints conformed to the patients’ individual geometries and expanded with airway growth (in the ‘fourth dimension’),” the researchers summarized.

“The three pediatric patients implanted with these 3-D–printed airway splints had a terminal form of TBM. The clinical improvement in each case was immediate and sustained, suggesting that improvement is not attributable to the natural history of the disease alone,” they concluded.

The study was funded by the National Institutes of Health. Two of the study authors were coinventors of the device for which they have filed a patent. There were no other disclosures.

[email protected]

Bioengineered tissues are showing promise in the treatment of valvular heart disease, according to the results of several early clinical and preclinical studies demonstrating the benefits of using heterologous substrates as scaffolding capable of promoting in vivo cell infiltration and remodeling.

Ultimately, cardiac tissue engineering seeks to develop the ideal material for replacement and repair of a variety of heart components – a material able to integrate, function, and, when necessary, grow and develop in a manner undifferentiated from normal cellular structures.

One of the most important areas of focus for such efforts is the development of heart valves and valve patches suitable for use in replacement or repair. The need is obvious: “The fact that literature continues to be published debating the best type of valve prosthesis is proof that, to date, the ideal valve substitute has not been found,” according to Cristian Rosu, Ph.D. and Dr. Edward G. Soltesz of the Cleveland Clinic (Semin Thorac Cardiovasc Surg. 2015 June 30 [doi: 10.1053/j.semtcvs.2015.06.007]).

Dr. Roşu and Dr. Soltesz go on to say that this lack of an ideal prosthetic heart valve leaves surgeons and their patients with a difficult choice at the time of valve surgery. The focus of their concern relates to how current bioprostheses are being used in younger and younger patients, and how these devices have a finite lifespan – requiring eventual reoperation and replacement, perhaps multiple times. In addition, calcification is a prominent and well-known risk of bioprosthetic valves, especially in children (Circulation. 2014 Jul 1;130[1]:51-60).

As for mechanical valves, although durable, they require a lifetime of anticoagulation therapy to prevent thrombosis. And the lack of growth potential found in both mechanical and current bioprosthetic devices is obviously a bane to pediatric valve therapy.

The latest efforts in tissue engineering therefore seek to develop valves and valve components that may be more permanent solutions by better mimicking natural valves.

But better mimicking of a natural valve is not an easy task, when such valves exist in “a near-perfect correlation of structure and function, enabling the valve to avoid excess stress on the cusps while simultaneously withstanding the wear and tear of 40-million repetitive deformations per year, equivalent to some 3 billion over a 75-year lifetime.” (“Principles of Tissue Engineering,” 4th ed. [London: Academic Press 2014, p. 813]).

The “holy grail” of tissue engineering, therefore, is to provide a completely in vitro–developed, autologous, fully cellularized, functional scaffolding for implantation that can live up to these requirements. In order to do this, extensive research into the search for the best cell sources and growth matrices and methods is underway, as illustrated by several recent reviews (Front Cell Dev Biol. 30 June 2015 [doi.org/10.3389/fcell.2015.00039] and Mater Sci Eng C. 2015 March 1;48:556-65).

Candidate cell types include a variety of embryonic stem cells, as well as adult cell types that have proven amenable to rejuvenation and redifferentiation (Adv Drug Deliv Rev. 2014;69-70:254-69).

In one example of the quest for completely in vitro human-tissue designed valves, Dr. Jean Dubé of Laval University, Quebec, and his colleagues reported research on a human tissue–engineered trileaflet heart valve assembled in vitro using human fibroblasts. These cells self-assembled into living tissue sheets when cultured in the presence of sodium ascorbate. These sheets could be layered together to create a thick construct, with the ultimate goal of replacing the use of bovine pericardium tissue implants with ones made of autologous cells from the patient (Acta Biomater. 2014 Aug;10[8]:3563-70).

Currently, however, many of the preclinical studies of fully tissue engineered heart valves have shown retraction of the heart valve leaflets as a major mechanism of functional failure. This retraction is caused by both passive and active cell stress and passive matrix stress, according to a review by Inge A.E.W. van Loosdregt, Ph.D., and her colleagues at the Eindhoven (the Netherlands) University of Technology (J Biomech. 2014 Jun 27;47[9]:2064-9).

While all of these developmental issues regarding the use of fully tissue-engineered valves are being worked out, early clinical applications are already being found for a new generation of valve prostheses that take an intermediate approach, one that uses an implanted scaffolding material that allows autologous cell infiltration and replacement in vivo.

Two of the most prominent examples of these scaffoldings currently in investigation and in early clinical use for heart valve repair or replacement are the bovine pericardium-derived CardioCel (Admedus, Brisbane, Australia) and the porcine intestinal submucosa-derived CorMatrix ECM(CorMatrix Cardiovascular, Roswell, Ga.). CorMatrix ECM was approved by the Food and Drug Administration in 2005 for pericardial repair and reconstruction, and in 2007 for cardiac tissue repair. The FDA approved CardioCel in 2014 for use in the United States in pericardial closure and for the repair of cardiac and vascular defects in both adults and children.

Both technologies rely on the concept of matrix infiltration by autologous cells after implantation in order to create a living mimic of the patient’s own tissues.

CardioCel is a highly treated, bovine pericardium-derived, decellularized collagen matrix. It showed significant resistance to calcification in mitral and pulmonary implants in a juvenile sheep model as reported by Dr. Christian P. Brizard at Royal Children’s Hospital, Melbourne, and his colleagues (J Thorac Cardiovasc Surg. 2014 Dec;148[6]:3194-201). These investigators replaced the posterior leaflet of the mitral valve and one of the pulmonary valve cusps with patches in 10-month-old ewes. They compared the use of CardioCel in six ewes to a control group of four ewes repaired with autologous pericardium that was treated intraoperatively with glutaraldehyde, which is the standard default used at their institution for more than 2 decades as the best material for valve repair in their pediatric patients.

Courtesy of JTCVS/American Association for Thoracic Surgery

The primary end points of the study were thickening and calcium content. They found that all animals survived with normal valve echocardiography until sacrifice at 7 months. They reported that the bovine pericardium patches allowed accurate valve repair at both systemic and pulmonary pressure with preserved mechanical properties and more-controlled healing and without calcification as compared with the controls. (Calcification is a known major risk factor for the eventual failure of bioprosthetic valves.) Additionally, the bovine pericardium patched valves showed the in vivo development of dense but thin cellularized outer layers of mature collagen I, compared with the controls, which had outer layers that were much less dense and showed the presence of immature collagen III.

In another case of valvular use of the CardioCel material, at the recent American Association for Thoracic Surgery Mitral Conclave 2015, M. Bonnie Ghosh-Dastidar, Ph.D., and her colleagues from the Royal Brompton Hospital, London, reported on a severely ill patient with significant mitral regurgitation and an infected mitral valve with large vegetations on the anterior leaflets. The infected tissue was resected and a large patch of CardioCel bovine pericardium was used to reconstruct the leaflets. Postoperative assessment showed a competent mitral valve with good area of leaflet coaptation, according to Dr. Ghosh-Dastidar.

In his invited commentary on the animal-model research by Dr. Brizard, Dr. Niv Ad, director of cardiac surgery research at Inova Heart and Vascular Institute, Falls Church, Va., said that despite the promise of the CardioCel patches, there were a number of alternative approaches being investigated. “Other engineered materials currently being study include processes such as lyophilization, which has shown promising results in reducing inflammation. Another proposed approach is the use of decellularized vessels and patches with the promise of normal remodeling and growth, such as extracellular matrix and its potential for tissue regeneration.”

Dr. Ad also stated that, “the key bioengineering challenge is to determine how biologic, structural, and mechanical factors interact and function in vivo. The understanding of these factors will prove critical to the development of a clinically viable tissue-engineered heart valve,” (J Thorac Cardiovasc Surg. 2014 Dec;148[6]:3202-3).

Courtesy of JTCVS/American Association for Thoracic Surgery

An example of the use of extracellular matrix material referred to by Dr. Ad is the CorMatrix ECM, which is an extracellular matrix material derived from porcine small-intestinal submucosa, processed and decellularized.

Dr. Marc W. Gerdisch and his colleagues from the Franciscan St. Francis Heart Center, Indianapolis, reported on the results of treating 19 patients with mitral valve disease using the CorMatrix patch material for partial or subtotal leaflet repair or extension. There were three deaths unrelated to the repair and no instances of perioperative or late stroke. Two patients with a history of cancer and cancer therapy experienced failure of the initial repair, requiring reintervention. However, the other mitral valve repair patients continued to show good valvular function and no calcification on echocardiographic follow-up of 4 days to 48 months (Thorac Cardiovasc Surg. 2014 Oct;148[4]:1370-8).

And in 2015, CorMatrix Cardiovascular announced FDA approval of an investigational device exemption for an early feasibility study of their CorMatrix ECM Tricuspid Heart Valve in up to 15 patients at 5 U.S. centers (NCT02397668). Indications are for the surgical management of tricuspid valve disease not amenable to annuloplasty or repair, including tricuspid valve disease secondary to congenital heart disease in pediatric patients and adult endocarditis patients. The CorMatrix ECM Tricuspid Valve is a flexible, unstented valve acting as a 3‐D scaffold designed to function immediately as a prosthetic, but one constructed to permit native cellular infiltration and remodeling.

Ultimately, both the CardioCel and the CorMatrix materials are just the tip of an iceberg of research into tissue engineering as a clinical tool. And success and the wider adoption of any current or developing technologies will require the results of far-more-extensive studies and long-term clinical results.

At some future date, engineered total organ substitutes or the routine injection of genetically engineered stem cells may provide a practical alternative for treating a diseased or damaged heart. But for now, the most-likely scenario is the continued exploration of tissue engineering to develop the most durable, growth-, stress-, and biologically compatible patches, valves, and vasculatures possible – defined tools that can be adapted to current surgical techniques, designed to obtain the best repair of congenital or acquired heart disease conditions.

As with any transformative technology in medicine, the path from laboratory success and optimistic short-term clinical results to durable, long-term postoperative benefits may be a rocky one. But given the current enthusiasm, it certainly looks as if it will be a well-traveled road.

Dr. Brizard reported consulting and lecturing fees from Admedus. His research was supported with the assistance of a grant from Admedus. Dr. Gerdisch reported consulting fees and equity ownership in CorMatrix Cardiovascular.

[email protected]

Bioengineered tissues are showing promise in the treatment of valvular heart disease, according to the results of several early clinical and preclinical studies demonstrating the benefits of using heterologous substrates as scaffolding capable of promoting in vivo cell infiltration and remodeling.

Ultimately, cardiac tissue engineering seeks to develop the ideal material for replacement and repair of a variety of heart components – a material able to integrate, function, and, when necessary, grow and develop in a manner undifferentiated from normal cellular structures.

One of the most important areas of focus for such efforts is the development of heart valves and valve patches suitable for use in replacement or repair. The need is obvious: “The fact that literature continues to be published debating the best type of valve prosthesis is proof that, to date, the ideal valve substitute has not been found,” according to Cristian Rosu, Ph.D. and Dr. Edward G. Soltesz of the Cleveland Clinic (Semin Thorac Cardiovasc Surg. 2015 June 30 [doi: 10.1053/j.semtcvs.2015.06.007]).

Dr. Roşu and Dr. Soltesz go on to say that this lack of an ideal prosthetic heart valve leaves surgeons and their patients with a difficult choice at the time of valve surgery. The focus of their concern relates to how current bioprostheses are being used in younger and younger patients, and how these devices have a finite lifespan – requiring eventual reoperation and replacement, perhaps multiple times. In addition, calcification is a prominent and well-known risk of bioprosthetic valves, especially in children (Circulation. 2014 Jul 1;130[1]:51-60).

As for mechanical valves, although durable, they require a lifetime of anticoagulation therapy to prevent thrombosis. And the lack of growth potential found in both mechanical and current bioprosthetic devices is obviously a bane to pediatric valve therapy.

The latest efforts in tissue engineering therefore seek to develop valves and valve components that may be more permanent solutions by better mimicking natural valves.

But better mimicking of a natural valve is not an easy task, when such valves exist in “a near-perfect correlation of structure and function, enabling the valve to avoid excess stress on the cusps while simultaneously withstanding the wear and tear of 40-million repetitive deformations per year, equivalent to some 3 billion over a 75-year lifetime.” (“Principles of Tissue Engineering,” 4th ed. [London: Academic Press 2014, p. 813]).

The “holy grail” of tissue engineering, therefore, is to provide a completely in vitro–developed, autologous, fully cellularized, functional scaffolding for implantation that can live up to these requirements. In order to do this, extensive research into the search for the best cell sources and growth matrices and methods is underway, as illustrated by several recent reviews (Front Cell Dev Biol. 30 June 2015 [doi.org/10.3389/fcell.2015.00039] and Mater Sci Eng C. 2015 March 1;48:556-65).

Candidate cell types include a variety of embryonic stem cells, as well as adult cell types that have proven amenable to rejuvenation and redifferentiation (Adv Drug Deliv Rev. 2014;69-70:254-69).

In one example of the quest for completely in vitro human-tissue designed valves, Dr. Jean Dubé of Laval University, Quebec, and his colleagues reported research on a human tissue–engineered trileaflet heart valve assembled in vitro using human fibroblasts. These cells self-assembled into living tissue sheets when cultured in the presence of sodium ascorbate. These sheets could be layered together to create a thick construct, with the ultimate goal of replacing the use of bovine pericardium tissue implants with ones made of autologous cells from the patient (Acta Biomater. 2014 Aug;10[8]:3563-70).

Currently, however, many of the preclinical studies of fully tissue engineered heart valves have shown retraction of the heart valve leaflets as a major mechanism of functional failure. This retraction is caused by both passive and active cell stress and passive matrix stress, according to a review by Inge A.E.W. van Loosdregt, Ph.D., and her colleagues at the Eindhoven (the Netherlands) University of Technology (J Biomech. 2014 Jun 27;47[9]:2064-9).

While all of these developmental issues regarding the use of fully tissue-engineered valves are being worked out, early clinical applications are already being found for a new generation of valve prostheses that take an intermediate approach, one that uses an implanted scaffolding material that allows autologous cell infiltration and replacement in vivo.

Two of the most prominent examples of these scaffoldings currently in investigation and in early clinical use for heart valve repair or replacement are the bovine pericardium-derived CardioCel (Admedus, Brisbane, Australia) and the porcine intestinal submucosa-derived CorMatrix ECM(CorMatrix Cardiovascular, Roswell, Ga.). CorMatrix ECM was approved by the Food and Drug Administration in 2005 for pericardial repair and reconstruction, and in 2007 for cardiac tissue repair. The FDA approved CardioCel in 2014 for use in the United States in pericardial closure and for the repair of cardiac and vascular defects in both adults and children.

Both technologies rely on the concept of matrix infiltration by autologous cells after implantation in order to create a living mimic of the patient’s own tissues.

CardioCel is a highly treated, bovine pericardium-derived, decellularized collagen matrix. It showed significant resistance to calcification in mitral and pulmonary implants in a juvenile sheep model as reported by Dr. Christian P. Brizard at Royal Children’s Hospital, Melbourne, and his colleagues (J Thorac Cardiovasc Surg. 2014 Dec;148[6]:3194-201). These investigators replaced the posterior leaflet of the mitral valve and one of the pulmonary valve cusps with patches in 10-month-old ewes. They compared the use of CardioCel in six ewes to a control group of four ewes repaired with autologous pericardium that was treated intraoperatively with glutaraldehyde, which is the standard default used at their institution for more than 2 decades as the best material for valve repair in their pediatric patients.

Courtesy of JTCVS/American Association for Thoracic Surgery

The primary end points of the study were thickening and calcium content. They found that all animals survived with normal valve echocardiography until sacrifice at 7 months. They reported that the bovine pericardium patches allowed accurate valve repair at both systemic and pulmonary pressure with preserved mechanical properties and more-controlled healing and without calcification as compared with the controls. (Calcification is a known major risk factor for the eventual failure of bioprosthetic valves.) Additionally, the bovine pericardium patched valves showed the in vivo development of dense but thin cellularized outer layers of mature collagen I, compared with the controls, which had outer layers that were much less dense and showed the presence of immature collagen III.

In another case of valvular use of the CardioCel material, at the recent American Association for Thoracic Surgery Mitral Conclave 2015, M. Bonnie Ghosh-Dastidar, Ph.D., and her colleagues from the Royal Brompton Hospital, London, reported on a severely ill patient with significant mitral regurgitation and an infected mitral valve with large vegetations on the anterior leaflets. The infected tissue was resected and a large patch of CardioCel bovine pericardium was used to reconstruct the leaflets. Postoperative assessment showed a competent mitral valve with good area of leaflet coaptation, according to Dr. Ghosh-Dastidar.

In his invited commentary on the animal-model research by Dr. Brizard, Dr. Niv Ad, director of cardiac surgery research at Inova Heart and Vascular Institute, Falls Church, Va., said that despite the promise of the CardioCel patches, there were a number of alternative approaches being investigated. “Other engineered materials currently being study include processes such as lyophilization, which has shown promising results in reducing inflammation. Another proposed approach is the use of decellularized vessels and patches with the promise of normal remodeling and growth, such as extracellular matrix and its potential for tissue regeneration.”

Dr. Ad also stated that, “the key bioengineering challenge is to determine how biologic, structural, and mechanical factors interact and function in vivo. The understanding of these factors will prove critical to the development of a clinically viable tissue-engineered heart valve,” (J Thorac Cardiovasc Surg. 2014 Dec;148[6]:3202-3).

Courtesy of JTCVS/American Association for Thoracic Surgery

An example of the use of extracellular matrix material referred to by Dr. Ad is the CorMatrix ECM, which is an extracellular matrix material derived from porcine small-intestinal submucosa, processed and decellularized.

Dr. Marc W. Gerdisch and his colleagues from the Franciscan St. Francis Heart Center, Indianapolis, reported on the results of treating 19 patients with mitral valve disease using the CorMatrix patch material for partial or subtotal leaflet repair or extension. There were three deaths unrelated to the repair and no instances of perioperative or late stroke. Two patients with a history of cancer and cancer therapy experienced failure of the initial repair, requiring reintervention. However, the other mitral valve repair patients continued to show good valvular function and no calcification on echocardiographic follow-up of 4 days to 48 months (Thorac Cardiovasc Surg. 2014 Oct;148[4]:1370-8).

And in 2015, CorMatrix Cardiovascular announced FDA approval of an investigational device exemption for an early feasibility study of their CorMatrix ECM Tricuspid Heart Valve in up to 15 patients at 5 U.S. centers (NCT02397668). Indications are for the surgical management of tricuspid valve disease not amenable to annuloplasty or repair, including tricuspid valve disease secondary to congenital heart disease in pediatric patients and adult endocarditis patients. The CorMatrix ECM Tricuspid Valve is a flexible, unstented valve acting as a 3‐D scaffold designed to function immediately as a prosthetic, but one constructed to permit native cellular infiltration and remodeling.

Ultimately, both the CardioCel and the CorMatrix materials are just the tip of an iceberg of research into tissue engineering as a clinical tool. And success and the wider adoption of any current or developing technologies will require the results of far-more-extensive studies and long-term clinical results.

At some future date, engineered total organ substitutes or the routine injection of genetically engineered stem cells may provide a practical alternative for treating a diseased or damaged heart. But for now, the most-likely scenario is the continued exploration of tissue engineering to develop the most durable, growth-, stress-, and biologically compatible patches, valves, and vasculatures possible – defined tools that can be adapted to current surgical techniques, designed to obtain the best repair of congenital or acquired heart disease conditions.

As with any transformative technology in medicine, the path from laboratory success and optimistic short-term clinical results to durable, long-term postoperative benefits may be a rocky one. But given the current enthusiasm, it certainly looks as if it will be a well-traveled road.

Dr. Brizard reported consulting and lecturing fees from Admedus. His research was supported with the assistance of a grant from Admedus. Dr. Gerdisch reported consulting fees and equity ownership in CorMatrix Cardiovascular.

[email protected]

Bioengineered tissues are showing promise in the treatment of valvular heart disease, according to the results of several early clinical and preclinical studies demonstrating the benefits of using heterologous substrates as scaffolding capable of promoting in vivo cell infiltration and remodeling.

Ultimately, cardiac tissue engineering seeks to develop the ideal material for replacement and repair of a variety of heart components – a material able to integrate, function, and, when necessary, grow and develop in a manner undifferentiated from normal cellular structures.

One of the most important areas of focus for such efforts is the development of heart valves and valve patches suitable for use in replacement or repair. The need is obvious: “The fact that literature continues to be published debating the best type of valve prosthesis is proof that, to date, the ideal valve substitute has not been found,” according to Cristian Rosu, Ph.D. and Dr. Edward G. Soltesz of the Cleveland Clinic (Semin Thorac Cardiovasc Surg. 2015 June 30 [doi: 10.1053/j.semtcvs.2015.06.007]).

Dr. Roşu and Dr. Soltesz go on to say that this lack of an ideal prosthetic heart valve leaves surgeons and their patients with a difficult choice at the time of valve surgery. The focus of their concern relates to how current bioprostheses are being used in younger and younger patients, and how these devices have a finite lifespan – requiring eventual reoperation and replacement, perhaps multiple times. In addition, calcification is a prominent and well-known risk of bioprosthetic valves, especially in children (Circulation. 2014 Jul 1;130[1]:51-60).

As for mechanical valves, although durable, they require a lifetime of anticoagulation therapy to prevent thrombosis. And the lack of growth potential found in both mechanical and current bioprosthetic devices is obviously a bane to pediatric valve therapy.

The latest efforts in tissue engineering therefore seek to develop valves and valve components that may be more permanent solutions by better mimicking natural valves.

But better mimicking of a natural valve is not an easy task, when such valves exist in “a near-perfect correlation of structure and function, enabling the valve to avoid excess stress on the cusps while simultaneously withstanding the wear and tear of 40-million repetitive deformations per year, equivalent to some 3 billion over a 75-year lifetime.” (“Principles of Tissue Engineering,” 4th ed. [London: Academic Press 2014, p. 813]).

The “holy grail” of tissue engineering, therefore, is to provide a completely in vitro–developed, autologous, fully cellularized, functional scaffolding for implantation that can live up to these requirements. In order to do this, extensive research into the search for the best cell sources and growth matrices and methods is underway, as illustrated by several recent reviews (Front Cell Dev Biol. 30 June 2015 [doi.org/10.3389/fcell.2015.00039] and Mater Sci Eng C. 2015 March 1;48:556-65).

Candidate cell types include a variety of embryonic stem cells, as well as adult cell types that have proven amenable to rejuvenation and redifferentiation (Adv Drug Deliv Rev. 2014;69-70:254-69).

In one example of the quest for completely in vitro human-tissue designed valves, Dr. Jean Dubé of Laval University, Quebec, and his colleagues reported research on a human tissue–engineered trileaflet heart valve assembled in vitro using human fibroblasts. These cells self-assembled into living tissue sheets when cultured in the presence of sodium ascorbate. These sheets could be layered together to create a thick construct, with the ultimate goal of replacing the use of bovine pericardium tissue implants with ones made of autologous cells from the patient (Acta Biomater. 2014 Aug;10[8]:3563-70).

Currently, however, many of the preclinical studies of fully tissue engineered heart valves have shown retraction of the heart valve leaflets as a major mechanism of functional failure. This retraction is caused by both passive and active cell stress and passive matrix stress, according to a review by Inge A.E.W. van Loosdregt, Ph.D., and her colleagues at the Eindhoven (the Netherlands) University of Technology (J Biomech. 2014 Jun 27;47[9]:2064-9).

While all of these developmental issues regarding the use of fully tissue-engineered valves are being worked out, early clinical applications are already being found for a new generation of valve prostheses that take an intermediate approach, one that uses an implanted scaffolding material that allows autologous cell infiltration and replacement in vivo.

Two of the most prominent examples of these scaffoldings currently in investigation and in early clinical use for heart valve repair or replacement are the bovine pericardium-derived CardioCel (Admedus, Brisbane, Australia) and the porcine intestinal submucosa-derived CorMatrix ECM(CorMatrix Cardiovascular, Roswell, Ga.). CorMatrix ECM was approved by the Food and Drug Administration in 2005 for pericardial repair and reconstruction, and in 2007 for cardiac tissue repair. The FDA approved CardioCel in 2014 for use in the United States in pericardial closure and for the repair of cardiac and vascular defects in both adults and children.

Both technologies rely on the concept of matrix infiltration by autologous cells after implantation in order to create a living mimic of the patient’s own tissues.

CardioCel is a highly treated, bovine pericardium-derived, decellularized collagen matrix. It showed significant resistance to calcification in mitral and pulmonary implants in a juvenile sheep model as reported by Dr. Christian P. Brizard at Royal Children’s Hospital, Melbourne, and his colleagues (J Thorac Cardiovasc Surg. 2014 Dec;148[6]:3194-201). These investigators replaced the posterior leaflet of the mitral valve and one of the pulmonary valve cusps with patches in 10-month-old ewes. They compared the use of CardioCel in six ewes to a control group of four ewes repaired with autologous pericardium that was treated intraoperatively with glutaraldehyde, which is the standard default used at their institution for more than 2 decades as the best material for valve repair in their pediatric patients.

Courtesy of JTCVS/American Association for Thoracic Surgery

The primary end points of the study were thickening and calcium content. They found that all animals survived with normal valve echocardiography until sacrifice at 7 months. They reported that the bovine pericardium patches allowed accurate valve repair at both systemic and pulmonary pressure with preserved mechanical properties and more-controlled healing and without calcification as compared with the controls. (Calcification is a known major risk factor for the eventual failure of bioprosthetic valves.) Additionally, the bovine pericardium patched valves showed the in vivo development of dense but thin cellularized outer layers of mature collagen I, compared with the controls, which had outer layers that were much less dense and showed the presence of immature collagen III.

In another case of valvular use of the CardioCel material, at the recent American Association for Thoracic Surgery Mitral Conclave 2015, M. Bonnie Ghosh-Dastidar, Ph.D., and her colleagues from the Royal Brompton Hospital, London, reported on a severely ill patient with significant mitral regurgitation and an infected mitral valve with large vegetations on the anterior leaflets. The infected tissue was resected and a large patch of CardioCel bovine pericardium was used to reconstruct the leaflets. Postoperative assessment showed a competent mitral valve with good area of leaflet coaptation, according to Dr. Ghosh-Dastidar.

In his invited commentary on the animal-model research by Dr. Brizard, Dr. Niv Ad, director of cardiac surgery research at Inova Heart and Vascular Institute, Falls Church, Va., said that despite the promise of the CardioCel patches, there were a number of alternative approaches being investigated. “Other engineered materials currently being study include processes such as lyophilization, which has shown promising results in reducing inflammation. Another proposed approach is the use of decellularized vessels and patches with the promise of normal remodeling and growth, such as extracellular matrix and its potential for tissue regeneration.”

Dr. Ad also stated that, “the key bioengineering challenge is to determine how biologic, structural, and mechanical factors interact and function in vivo. The understanding of these factors will prove critical to the development of a clinically viable tissue-engineered heart valve,” (J Thorac Cardiovasc Surg. 2014 Dec;148[6]:3202-3).

Courtesy of JTCVS/American Association for Thoracic Surgery

An example of the use of extracellular matrix material referred to by Dr. Ad is the CorMatrix ECM, which is an extracellular matrix material derived from porcine small-intestinal submucosa, processed and decellularized.

Dr. Marc W. Gerdisch and his colleagues from the Franciscan St. Francis Heart Center, Indianapolis, reported on the results of treating 19 patients with mitral valve disease using the CorMatrix patch material for partial or subtotal leaflet repair or extension. There were three deaths unrelated to the repair and no instances of perioperative or late stroke. Two patients with a history of cancer and cancer therapy experienced failure of the initial repair, requiring reintervention. However, the other mitral valve repair patients continued to show good valvular function and no calcification on echocardiographic follow-up of 4 days to 48 months (Thorac Cardiovasc Surg. 2014 Oct;148[4]:1370-8).

And in 2015, CorMatrix Cardiovascular announced FDA approval of an investigational device exemption for an early feasibility study of their CorMatrix ECM Tricuspid Heart Valve in up to 15 patients at 5 U.S. centers (NCT02397668). Indications are for the surgical management of tricuspid valve disease not amenable to annuloplasty or repair, including tricuspid valve disease secondary to congenital heart disease in pediatric patients and adult endocarditis patients. The CorMatrix ECM Tricuspid Valve is a flexible, unstented valve acting as a 3‐D scaffold designed to function immediately as a prosthetic, but one constructed to permit native cellular infiltration and remodeling.

Ultimately, both the CardioCel and the CorMatrix materials are just the tip of an iceberg of research into tissue engineering as a clinical tool. And success and the wider adoption of any current or developing technologies will require the results of far-more-extensive studies and long-term clinical results.

At some future date, engineered total organ substitutes or the routine injection of genetically engineered stem cells may provide a practical alternative for treating a diseased or damaged heart. But for now, the most-likely scenario is the continued exploration of tissue engineering to develop the most durable, growth-, stress-, and biologically compatible patches, valves, and vasculatures possible – defined tools that can be adapted to current surgical techniques, designed to obtain the best repair of congenital or acquired heart disease conditions.

As with any transformative technology in medicine, the path from laboratory success and optimistic short-term clinical results to durable, long-term postoperative benefits may be a rocky one. But given the current enthusiasm, it certainly looks as if it will be a well-traveled road.

Dr. Brizard reported consulting and lecturing fees from Admedus. His research was supported with the assistance of a grant from Admedus. Dr. Gerdisch reported consulting fees and equity ownership in CorMatrix Cardiovascular.

[email protected]

Esophageal adenocarcinoma is fatal to 90% of patients, indicating a profound need for new therapeutic agents, according to Zhuewn Wang and her colleagues.

The search for genes involved in oncogenesis provides one avenue for finding potential targets. Ms. Wang and her colleagues performed a laboratory study at the University of Michigan, Ann Arbor, to examine the results of the overexpression of DKK3 (the gene for the Dickkopf-3 protein [DKK3]) in DKK3-transfected tissue-cultured esophageal adenocarcinoma (EAC) cell lines. They found that DKK3 overexpression correlated with significantly increased proliferation and Matrigel invasion ability – both known to be important oncogenic traits (J. Thorac. Cardiovasc. Surg. 2015;150:377-85).

Courtesy of the American Association for Thoracic Surgery

DKK3 was overexpressed (greater than twofold) in 76% (72/95) of esophageal adenocarcinomas tested. In addition, the DKK3 protein was present at moderate to high levels in 47% (29/62) of esophageal adenocarcinomas as shown by tissue microarray. Nodal metastases were also significantly increased in patients with esophageal adenocarcinomas highly overexpressing DKK3 (28/32) vs. non–highly expressing EAC tumors (42/63).

In vitro studies showed that stable transfection of DKK3 in an EAC cell line significantly increased proliferation and Matrigel invasion. The researchers also found that the levels of SMAD4, a key mediator of the transforming growth factor–beta pathway, increased after activin treatment of the transfected cell line, and siSMAD4 significantly decreased Matrigel invasion, suggesting that DKK3 acts through the transforming growth factor–beta pathway, according to the researchers.

Additionally, the transfected cells showed increased endothelial tube formation, and they were significantly more resistant to 5-fluorouracil and cisplatin. This finding correlates with the fact that DKK3 expression was found to be significantly higher in chemoresistant esophageal adenocarcinomas, the investigators reported.

In their animal model system (NOD/SCIDg mice), injection of the transfected cells resulted in tumors at all sites (8/8), whereas vector-only cells grew in only one of eight sites.

“The results of the current study suggest that DKK3 may play an important role in tumor growth and invasion in EAC. DKK3 is overexpressed in a significant number of esophageal adenocarcinomas and targeting DKK3 and its downstream mediators may be beneficial in the prevention and treatment of micrometastatic disease and potentially decreasing disease recurrence,” the researchers concluded.

The authors reported that they had no relevant financial conflicts.

[email protected]

Esophageal adenocarcinoma is fatal to 90% of patients, indicating a profound need for new therapeutic agents, according to Zhuewn Wang and her colleagues.

The search for genes involved in oncogenesis provides one avenue for finding potential targets. Ms. Wang and her colleagues performed a laboratory study at the University of Michigan, Ann Arbor, to examine the results of the overexpression of DKK3 (the gene for the Dickkopf-3 protein [DKK3]) in DKK3-transfected tissue-cultured esophageal adenocarcinoma (EAC) cell lines. They found that DKK3 overexpression correlated with significantly increased proliferation and Matrigel invasion ability – both known to be important oncogenic traits (J. Thorac. Cardiovasc. Surg. 2015;150:377-85).

Courtesy of the American Association for Thoracic Surgery

DKK3 was overexpressed (greater than twofold) in 76% (72/95) of esophageal adenocarcinomas tested. In addition, the DKK3 protein was present at moderate to high levels in 47% (29/62) of esophageal adenocarcinomas as shown by tissue microarray. Nodal metastases were also significantly increased in patients with esophageal adenocarcinomas highly overexpressing DKK3 (28/32) vs. non–highly expressing EAC tumors (42/63).

In vitro studies showed that stable transfection of DKK3 in an EAC cell line significantly increased proliferation and Matrigel invasion. The researchers also found that the levels of SMAD4, a key mediator of the transforming growth factor–beta pathway, increased after activin treatment of the transfected cell line, and siSMAD4 significantly decreased Matrigel invasion, suggesting that DKK3 acts through the transforming growth factor–beta pathway, according to the researchers.

Additionally, the transfected cells showed increased endothelial tube formation, and they were significantly more resistant to 5-fluorouracil and cisplatin. This finding correlates with the fact that DKK3 expression was found to be significantly higher in chemoresistant esophageal adenocarcinomas, the investigators reported.

In their animal model system (NOD/SCIDg mice), injection of the transfected cells resulted in tumors at all sites (8/8), whereas vector-only cells grew in only one of eight sites.

“The results of the current study suggest that DKK3 may play an important role in tumor growth and invasion in EAC. DKK3 is overexpressed in a significant number of esophageal adenocarcinomas and targeting DKK3 and its downstream mediators may be beneficial in the prevention and treatment of micrometastatic disease and potentially decreasing disease recurrence,” the researchers concluded.

The authors reported that they had no relevant financial conflicts.

[email protected]

Esophageal adenocarcinoma is fatal to 90% of patients, indicating a profound need for new therapeutic agents, according to Zhuewn Wang and her colleagues.

The search for genes involved in oncogenesis provides one avenue for finding potential targets. Ms. Wang and her colleagues performed a laboratory study at the University of Michigan, Ann Arbor, to examine the results of the overexpression of DKK3 (the gene for the Dickkopf-3 protein [DKK3]) in DKK3-transfected tissue-cultured esophageal adenocarcinoma (EAC) cell lines. They found that DKK3 overexpression correlated with significantly increased proliferation and Matrigel invasion ability – both known to be important oncogenic traits (J. Thorac. Cardiovasc. Surg. 2015;150:377-85).

Courtesy of the American Association for Thoracic Surgery

DKK3 was overexpressed (greater than twofold) in 76% (72/95) of esophageal adenocarcinomas tested. In addition, the DKK3 protein was present at moderate to high levels in 47% (29/62) of esophageal adenocarcinomas as shown by tissue microarray. Nodal metastases were also significantly increased in patients with esophageal adenocarcinomas highly overexpressing DKK3 (28/32) vs. non–highly expressing EAC tumors (42/63).

In vitro studies showed that stable transfection of DKK3 in an EAC cell line significantly increased proliferation and Matrigel invasion. The researchers also found that the levels of SMAD4, a key mediator of the transforming growth factor–beta pathway, increased after activin treatment of the transfected cell line, and siSMAD4 significantly decreased Matrigel invasion, suggesting that DKK3 acts through the transforming growth factor–beta pathway, according to the researchers.

Additionally, the transfected cells showed increased endothelial tube formation, and they were significantly more resistant to 5-fluorouracil and cisplatin. This finding correlates with the fact that DKK3 expression was found to be significantly higher in chemoresistant esophageal adenocarcinomas, the investigators reported.

In their animal model system (NOD/SCIDg mice), injection of the transfected cells resulted in tumors at all sites (8/8), whereas vector-only cells grew in only one of eight sites.

“The results of the current study suggest that DKK3 may play an important role in tumor growth and invasion in EAC. DKK3 is overexpressed in a significant number of esophageal adenocarcinomas and targeting DKK3 and its downstream mediators may be beneficial in the prevention and treatment of micrometastatic disease and potentially decreasing disease recurrence,” the researchers concluded.

The authors reported that they had no relevant financial conflicts.

[email protected]

Talent facilitates team performance, but only up to a point, depending on the type of team. For highly interdependent teams, there is a threshold where the benefits of more talent decrease and eventually become detrimental rather than beneficial, according to an analysis of five studies performed by Roderick I. Swaab and his colleagues.

Surveys across industries and countries show that organizations consider talent attraction is their top priority, presumably based on the belief that more talent is better and the relationship between talent and team performance is linear and monotonic, they stated in Psychological Science (2014;25:1581-91)

The researchers analyzed the results of five studies they performed to investigate this relationship, comparing the impact of talent on team performance in the highly interdependent sports soccer (World Cup performance) and basketball (NBA), compared with the less interdependent sport of baseball (MLB).

In the case of soccer, team performance data were based on the average Fédération Internationale de Football Association (FIFA) rankings of national teams during the 2010 and 2014 World Cup qualification periods. Top talent was assessed by dividing the team’s numbers of players in each national team active in one of the world’s elite clubs divided by the total number of players on the national team.

In the case of the NBA, top talent was determined using the individual players’ estimated wins added (EWA) as determined over a 10-year period (2002-2012), with an index determining whether a player was in the top one-third (1) or not (0). Team performance was measured using each team’s end-of-year win percentage.

For baseball, top talent was determined using a player’s wins above replacement statistic (WAR), which is the number of wins a player contributes relative to a freely available minor-league player. Team performance was measured using each team’s win percentage.

In their results, basketball and soccer, the two most interdependent of the three sports, both showed a significant quadratic effect in which top talent benefited performance only up to a point, after which the marginal benefit of talent decreased and turned negative.

These results were in contrast to those seen with baseball. “As we predicted, the effect of top talent never turned negative in baseball, a sport in which task interdependence is relatively low. Thus there was no too-much-talent effect in baseball unlike in football [soccer] and basketball” according to the researchers.

“We predict that the too-much-talent effect will be found in other organizational contexts as well,” they added.

“Just as a colony of high-performing chickens competing for dominance suffers decrements in overall egg production and increases in bird mortality, teams with too much talent appear to divert attention away from coordination as team members peck at each other in their attempts to establish intergroup standing. In many cases, too much talent can be the seed of failure,” Mr. Swaab and his colleagues concluded.

The authors all declared that they had no conflicts of interest relative to the paper.

[email protected]

Talent facilitates team performance, but only up to a point, depending on the type of team. For highly interdependent teams, there is a threshold where the benefits of more talent decrease and eventually become detrimental rather than beneficial, according to an analysis of five studies performed by Roderick I. Swaab and his colleagues.

Surveys across industries and countries show that organizations consider talent attraction is their top priority, presumably based on the belief that more talent is better and the relationship between talent and team performance is linear and monotonic, they stated in Psychological Science (2014;25:1581-91)

The researchers analyzed the results of five studies they performed to investigate this relationship, comparing the impact of talent on team performance in the highly interdependent sports soccer (World Cup performance) and basketball (NBA), compared with the less interdependent sport of baseball (MLB).

In the case of soccer, team performance data were based on the average Fédération Internationale de Football Association (FIFA) rankings of national teams during the 2010 and 2014 World Cup qualification periods. Top talent was assessed by dividing the team’s numbers of players in each national team active in one of the world’s elite clubs divided by the total number of players on the national team.

In the case of the NBA, top talent was determined using the individual players’ estimated wins added (EWA) as determined over a 10-year period (2002-2012), with an index determining whether a player was in the top one-third (1) or not (0). Team performance was measured using each team’s end-of-year win percentage.

For baseball, top talent was determined using a player’s wins above replacement statistic (WAR), which is the number of wins a player contributes relative to a freely available minor-league player. Team performance was measured using each team’s win percentage.

In their results, basketball and soccer, the two most interdependent of the three sports, both showed a significant quadratic effect in which top talent benefited performance only up to a point, after which the marginal benefit of talent decreased and turned negative.

These results were in contrast to those seen with baseball. “As we predicted, the effect of top talent never turned negative in baseball, a sport in which task interdependence is relatively low. Thus there was no too-much-talent effect in baseball unlike in football [soccer] and basketball” according to the researchers.

“We predict that the too-much-talent effect will be found in other organizational contexts as well,” they added.

“Just as a colony of high-performing chickens competing for dominance suffers decrements in overall egg production and increases in bird mortality, teams with too much talent appear to divert attention away from coordination as team members peck at each other in their attempts to establish intergroup standing. In many cases, too much talent can be the seed of failure,” Mr. Swaab and his colleagues concluded.

The authors all declared that they had no conflicts of interest relative to the paper.

[email protected]

Talent facilitates team performance, but only up to a point, depending on the type of team. For highly interdependent teams, there is a threshold where the benefits of more talent decrease and eventually become detrimental rather than beneficial, according to an analysis of five studies performed by Roderick I. Swaab and his colleagues.

Surveys across industries and countries show that organizations consider talent attraction is their top priority, presumably based on the belief that more talent is better and the relationship between talent and team performance is linear and monotonic, they stated in Psychological Science (2014;25:1581-91)

The researchers analyzed the results of five studies they performed to investigate this relationship, comparing the impact of talent on team performance in the highly interdependent sports soccer (World Cup performance) and basketball (NBA), compared with the less interdependent sport of baseball (MLB).

In the case of soccer, team performance data were based on the average Fédération Internationale de Football Association (FIFA) rankings of national teams during the 2010 and 2014 World Cup qualification periods. Top talent was assessed by dividing the team’s numbers of players in each national team active in one of the world’s elite clubs divided by the total number of players on the national team.

In the case of the NBA, top talent was determined using the individual players’ estimated wins added (EWA) as determined over a 10-year period (2002-2012), with an index determining whether a player was in the top one-third (1) or not (0). Team performance was measured using each team’s end-of-year win percentage.

For baseball, top talent was determined using a player’s wins above replacement statistic (WAR), which is the number of wins a player contributes relative to a freely available minor-league player. Team performance was measured using each team’s win percentage.

In their results, basketball and soccer, the two most interdependent of the three sports, both showed a significant quadratic effect in which top talent benefited performance only up to a point, after which the marginal benefit of talent decreased and turned negative.

These results were in contrast to those seen with baseball. “As we predicted, the effect of top talent never turned negative in baseball, a sport in which task interdependence is relatively low. Thus there was no too-much-talent effect in baseball unlike in football [soccer] and basketball” according to the researchers.

“We predict that the too-much-talent effect will be found in other organizational contexts as well,” they added.

“Just as a colony of high-performing chickens competing for dominance suffers decrements in overall egg production and increases in bird mortality, teams with too much talent appear to divert attention away from coordination as team members peck at each other in their attempts to establish intergroup standing. In many cases, too much talent can be the seed of failure,” Mr. Swaab and his colleagues concluded.

The authors all declared that they had no conflicts of interest relative to the paper.

[email protected]