Figure 1. The human foreskin shape after surgical removal: (a) schematic representation of human foreskin after surgical removal via circumcision and (b) representation of the sequential steps performed to identify the shape of the human foreskin after surgical removal via circumcision.
The practice of foreskin amputation, circumcision (Figure 1(b)), has ancient origins, but its modern incarnation can easily be traced to the late 19th century, where many Western practitioners introduced into standard medical practice various forms of medicalized genital injury for both males and females.11,12 A prevailing belief was that many physical and mental afflictions were rooted in masturbation and sexual promiscuity.11,12 Males were prescribed circumcision as a preventive, as it intentionally cripples natural function and dulls sexual pleasure.1113 Despite the explicit nature of these origins, the practice has persisted. It is difficult to determine precisely how many living males have been subjected to circumcision, voluntarily or otherwise, but a conservative estimate suggests that about 650 million males worldwide are circumcised (about 23% of the world’s male population).14 Moreover, there is a prodigious amount of ethical and moral issues regarding the practice of circumcising non-consenting minors when it is not medically warranted, as it infringes on one’s right to bodily autonomy,15 and many international medical and ethical institutions have lambasted the practice1618 and have refuted the modern medical justifications and supposed benefits of male circumcision.1923
Understandably, circumcision is associated with a plethora of complications. Most notably, males report a substantial decrease in sensitivity due to keratinization of the exposed glans and inner mucosa24 and the general loss of the densely innervated and reflexogenic tissue; circumcised males are far less sensitive than their intact counterparts.13,25 This state with diminished neuroreceptors, sensitivity, and vascularity, wrought by circumcision, is heavily associated with erectile dysfunction.2527 Ejacul-ation and orgasm are complex physiological responses to physical, emotional, and social processes and are not well-understood. What is known is that ejaculation is primarily dependent on afferent signals which originate in the encapsulated nerve endings of the glans, foreskin, and penile shaft skin, and the response is controlled heavily by the autonomic nervous system.28 The loss of the mechanical gliding and stretch receptors of the sensitive foreskin and frenulum is associated with delayed ejaculation or the inability to ejaculate.27,29,30 In addition, circumcised males suffer from premature ejaculation at higher rates than their intact counterparts.3133 This is believed to be due to the full exposure of the sensitive corona of the glans, which is more directly stimulated during intercourse in circumcised males.34
Circumcision is also associated with an unsurprising reduction in sexual pleasure.29,35 One survey of males circumcised as adults found 22 out of 38 said they regret their decision, as intercourse worsened.36 During intercourse, the immobile shaft skin of the circumcised member contributes to vaginal dryness and abrasion,37 leading to painful intercourse for female partners.31,37 The immobilized shaft skin can also lead to tight, painful erections35 and is susceptible to injury and pain during intercourse and masturbation.32 Loss of the foreskin’s gliding action causes circumcised males more difficulty in penetrating their respective partners,27 as the force required for penetration is increased 10-fold.38 Literature surveys show that there is no evidence that circumcision reduces the transmission of HIV or other sexually transmitted diseases (STDs).20,21 Despite this, circumcised males are far less likely to use condoms,39,40 likely due to decreased sensitivity. Males who have been subjected to involuntary circumcision have long reported emotional trauma, feelings of violation, and many other types of circumcision-related psychological distress.4042 This indicates that circumcision is not only an issue of ethics and morals but also one that pertains to public health, both physical and mental. More severe consequences of circumcision involve botched procedures and death, which are virtually always avoidable and caused by practitioner negligence.4347
Aggrieved with their circumcision status, some males seek to restore their ablated foreskins. Foreskin reconstruction methods have been in practice since at least the second century BCE, with the two methods, surgical and nonsurgical, changing very little since their inception.48 Surgical reconstruction methods traditionally involve autografts of skin from elsewhere on the body or manipulation of remaining penile shaft skin to reconstruct a pseudo-foreskin.49,50 Nonsurgical methods make use of tissue expansion: mechanical stress is applied to the residual shaft skin and over time the skin tube is lengthened, also resulting in a pseudo-foreskin.48 Currently, surgical methods have fallen out of popularity, as autografts are always fundamentally different from the natural foreskin, leading to poor cosmetic appearance and functionality, especially when compared to procedural costs.48,51 In addition, due to the difficulty of reconstructing the specialized foreskin tissue using currently available surgical methods, there are several instances of botched procedures, leaving patients with grim results.52 The current consensus is that nonsurgical tissue expansion methods are state of the art, as they produce a pseudo-foreskin with much higher cosmetic appearance and functionality than surgical methods, are far less expensive, and without the associated risks of surgical methods.53 Unfortunately, there is a significant learning curve associated with nonsurgical methods, is very time intensive, and it can take many years for one to complete their restoration efforts.48
Despite this, men who have completed restoration report increased sensitivity, improved sexual satisfaction, and the lessening or even resolution of their circumcision-related psychological distresses.5355 While some men highly regard the results of nonsurgical restoration, it is far from a perfect reconstruction. Circumcision always ablates the ridged band, and in some cases the frenulum as well.56 The other densely innervated portions of the foreskin are also lost, leaving only residual nervous tissue of the shaft skin.5 Tissue expansion cannot restore these specialized structures, and it is unclear whether the process promotes any nerve regeneration.5Touch-up surgeries can improve cosmetic appearance and functionality.48 However, results echo the natural form of the foreskin. Under this context, Foregen Onlus Association—an international, donor-funded non-profit company—is devoted to providing a solution to circumcised males who desire complete restoration of sexual sensation, mobility, lubrication, and other properties intrinsic to the foreskin, utilizing principles of Tissue Engineering & Regenerative Medicine, as well as building on previous work in surgical reconstruction. This approach intends to regenerate the ablated tissue as opposed to merely replacing it with a foreskin “substitute.” One-third of the tissue engineering triad is biomaterial scaffolding, and to that effect, the purpose of this study is to develop an extracellular matrix (ECM)-based biomaterial scaffold, derived from the human foreskin, on which a neoforeskin can be engineered. To accomplish this, a novel decellularization method,57 designed and realized at Emilia Romagna Regional Skin Bank, will be applied to donor foreskin tissue, and the mechanical, biological, and structural characteristics will be assessed for its prospective use as a tissue engineering scaffold.