The multi-layered skin structure includes the epidermis, dermis and hypodermis, which forms a sophisticated tissue composed of extracellular matrix (ECM). The wound repair is a well-orchestrated process when the skin is injured. However, this natural wound repair will be ineffective for large surface area wounds. Autografts-based treatment is efficient but, additional pain and secondary healing of the patient limits its successful application. Therefore, there is a substantial need for fabricating tissue-engineered skin constructs. The development of a successful skin graft requires a fundamental understanding of the natural skin and its healing process, as well as design criteria for selecting a biopolymer and an appropriate fabrication technique. Further, the fabrication of an appropriate skin graft needs to meet physicochemical, mechanical, and biological properties equivalent to the natural skin. Advanced 3D bioprinting provides spatial control of the placement of functional components, such as biopolymers with living cells, which can satisfy the prerequisites for the preparation of an ideal skin graft. In this view, here we elaborate on the basic design requirements, constraints involved in the fabrication of skin graft and choice of ink, the probable solution by 3D bioprinting technique, as well as their latest advancements, challenges, and prospects. 

Tissue engineered skin substitutes: A comprehensive review of basic design, fabrication using 3D printing, recent advances and challenges.

Design and translation of injectable biomaterials

OBJECTIVE
To determine the medium-term maternal impact of open fetal spina bifida repair.


DESIGN
Prospective cohort study.


SETTING
University Hospitals Leuven, Belgium.


POPULATION
Mothers who had open maternal-fetal spina bifida repair between March 2012 and December 2021.


METHODS
A patient-reported survey on subsequent fertility, pregnancy, and gynaecological and psychological outcomes.


MAIN OUTCOME MEASURES
Complications during subsequent pregnancies, and gynaecological and psychological problems.


RESULTS
Seventy-two out of 100 invited women completed the questionnaire (72%). Despite being advised not to, seven of 13 women attempting to conceive became pregnant within 2 years after fetal surgery and one woman delivered vaginally. Two of the 16 subsequent pregnancies were complicated by an open neural tube defect. One pregnancy was complicated by a placenta accreta and one pregnancy was complicated by a uterine rupture, both with good neonatal outcomes. Nearly half of respondents who did not attempt to conceive reported that this was because of their experience of the index pregnancy and caring for the index child. Three out of four respondents reported medium-term psychological problems, mostly anxiety for the health of the index child, fear for recurrence in subsequent pregnancies and feelings of guilt.


CONCLUSIONS
Open maternal-fetal surgery for spina bifida did not appear to affect fertility in our cohort. Half of the attempts to conceive took place within 2 years. One uterine rupture and one placenta accreta occurred in 16 subsequent pregnancies. Most respondents reported psychological problems linked to the index pregnancy, which reinforces the need for long-term psychological support.

Subsequent fertility, pregnancy, and gynaecological and psychological outcomes after maternal-fetal surgery for open spina bifida: A prospective cohort study.

The integration of barrier materials with pharmacological therapy is a promising strategy to treat intrauterine adhesions (IUAs). However, most of these materials are surgically implanted in a fixed shape and incongruence with the natural mechanical properties of the uterus, causing poor adaptability and significant discomfort to the patients. Herein, an injectable, biodegradable, and mechanically adaptive hydrogel loaded with platelet-rich plasma (PRP) is created by L‑serine and allyl functionalized chitosan (ACS) to achieve efficient, comfortable, and minimally invasive treatment of IUAs. L‑serine induces fast gelation and mechanical reinforcement of the hydrogel, while ACS introduces, imparting a good injectability and complaint yet strong feature to the hydrogel. This design enables the hydrogel to adapt to the complex geometry and match the mechanical properties of the uterine. Moreover, the hydrogel exhibits proper degradability, sustained growth factors (GFs) of PRP release ability, and good biocompatibility. Consequently, the hydrogel shows promising therapeutic efficacy by reducing collagen fiber deposition and facilitating endometrium cell proliferation, thereby restoring the fertility function of the uterus in an IUAs model of rats. Accordingly, the combination of L‑serine and ACS-induced hydrogel with such advantages holds great potential for treating IUAs. STATEMENT OF SIGNIFICANCE: This research introduces a breakthrough in the treatment of intrauterine adhesions (IUAs) with an injectable, biodegradable and mechanically adaptive hydrogel using L‑serine and allyl functionalized chitosan (ACS). Unlike traditional surgical treatments, this hydrogel uniquely conforms to the uterus's geometry and mechanical properties, offering a minimally invasive, comfortable, and more effective solution. The hydrogel is designed to release growth factors from platelet-rich plasma (PRP) sustainably, promoting tissue regeneration by enhancing collagen fiber deposition and endometrium cell proliferation. Demonstrated efficacy in a rat model of IUAs indicates its great potential to significantly improve fertility restoration treatments. This advancement represents a significant leap in reproductive medicine, promising to transform IUAs treatment with its innovative approach to achieving efficient, comfortable, and minimally invasive therapy. 

Injectable, degradable, and mechanically adaptive hydrogel induced by L-serine and allyl-functionalized chitosan with platelet-rich plasma for treating intrauterine adhesions

OBJECTIVE
Few fetal malformations benefit from in utero surgery. One of the major drawbacks of fetal surgery is preterm premature rupture of membranes (PPROM). Morbidity associated with congenital diaphragmatic hernia (CDH) is primarily respiratory but also gastrointestinal and induced prematurity are likely to worsens those complications. To assess whether or not the cannula insertion site on the maternal abdomen during fetoscopic endoluminal tracheal occlusion (FETO) was associated with PPROM before balloon removal.


METHODS
This multicenter retrospective study was conducted on consecutive pregnancies with isolated left- or right-sided CDH fetuses who underwent FETO in 4 centers between January 2009 and January 2021. The insertion site for balloon insertion was categorized as above or below the umbilicus. One propensity score was analyzed in both groups: entry above the umbilicus and entry below, to calculate an average treatment effect (ATE) by inverse probability of treatment weighting (IPTW). Afterwards, one logistic regression and one Cox proportional hazard regression that included the ATE weights were performed to examine the effect size of entry point on the frequency and timing of PPROM prior to the balloon removal procedure.


RESULTS
A total of 294 patients were included. Mean gestational age (GA) at PPROM was 33.50±2.01 weeks of gestation (WG) and the mean rate of PPROM was 25.8% (76/294). GA at FETO was later in the "below umbilicus" group (29.0±1.25 WG vs 29.47±1.29 WG, p=0.002) and the duration of FETO was longer in the "above umbilicus" group (14.49 min [interquartile range-IQR: 8.00-21.00] vs 11.00 min [IQR: 7.00-14.49], p=0.002). After balancing for possible confounding factors, entry point below the umbilicus did not increase the risk of PPROM (adjusted OR: 1.56, 95%CI: [0.89-2.74], p=0.120) and had no effect on the time point at membrane rupture (adjusted HR: 1.56, 95% CI: [0.95-2.55], p=0.080).


CONCLUSION
There was no evidence that uterine entry site was correlated with the risk of PPROM before balloon removal. This article is protected by copyright. All rights reserved.

Effect of cannula insertion site in fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia on preterm premature rupture of membranes.

Introduction: The benefits of fetal surgery are impaired by the high incidence of iatrogenic preterm prelabor rupture of the fetal membranes (iPPROM), for which chorioamniotic separation has been suggested as a potential initiator. Despite the urgent need to prevent iPPROM by sealing the fetoscopic puncture site after intervention, no approach has been clinically translated. Methods: A mussel-inspired biomimetic glue was tested in an ovine fetal membrane (FM) defect model. The gelation time of mussel glue (MG) was first optimized to make it technically compatible with fetal surgery. Then, the biomaterial was loaded in polytetrafluoroethylene-coated nitinol umbrella-shaped receptors and applied on ovine FM defects (N = 10) created with a 10 French trocar. Its sealing performance and tissue response were analyzed 10 days after implantation by amniotic fluid (AF) leakage and histological methods. Results: All ewes and fetuses recovered well after the surgery, and 100% ewe survival and 91% fetal survival were observed at explantation. All implants were tight at explantation, and no AF leakage was observed in any of them. Histological analysis revealed a mild tissue response to the implanted glue. Conclusion: MG showed promising properties for the sealing of FM defects and thereby the prevention of preterm birth. Studies to analyze the long-term tissue response to the sealant should be performed.

/pdf/in-vivo-sealing-of-fetoscopy-induced-fetal-membrane-defects-5qe8ndmj.pdf

In vivo Sealing of Fetoscopy-Induced Fetal Membrane Defects by Mussel Glue

Introduction: In select cases, in utero surgery for myelomeningocele (MMC) leads to better outcomes than postnatal repair. However, maternal HIV infection constitutes a formal exclusion criterion due to the potential of vertical HIV transmission. Encouraged by a previous case of a successful fetal spina bifida repair in a Hepatitis Bs antigen-positive woman, a plan was devised allowing for fetal surgery. Case Report: In utero MMC repair was performed although the mother was HIV-infected. To minimize the risk of in utero HIV transmission, the mother was treated by highly active antiretroviral therapy throughout gestation as well as intravenous zidovudine administration during maternal-fetal surgery. The mother tolerated all procedures very well without any sequelae. The currently 20 month-old toddler is HIV negative and has significantly benefitted from fetal surgery. Discussion/Conclusion: This case shows that maternal HIV is not a priori a diagnosis that excludes fetal surgery. Rather, it might be a surrogate for moving towards personalized medicine and away from applying too rigorous exclusion criteria in the selection of candidates for maternal-fetal surgery.

Fetal-Maternal Surgery for Spina Bifida in a HIV-Infected Mother

Introduction: Fetal spina bifida (SB) repair is a distinct therapeutic option in selected cases. Since this procedure may not only be associated with short-term obstetrical complications, the aim of this study was to assess the outcomes of subsequent pregnancies after open fetal SB repair. Methods: 138 patients having had open fetal SB repair at our center received a questionnaire regarding the occurrence, course, and outcome of subsequent pregnancies. Additionally, medical records were reviewed. All subsequent pregnancies with complete outcome data that progressed beyond 20 gestational weeks (GW) were included for further analysis. Results: 70% of all women answered the questionnaire. Out of this cohort, 35 subsequent pregnancies were reported in 29% of women. The rate of early pregnancy loss including elective terminations was 14%. All 29 pregnancies processing >20 GW ended in live births without preterm births <34th GW. Mean gestational age at delivery was 37.3 ± 1.4 GW. Uterine rupture occurred in two cases (7%) and uterine thinning/dehiscence was present in six cases (21%). No maternal transfusions were required. Conclusion: When counseling women undergoing open fetal SB repair, one should consider possible risks for subsequent pregnancies, especially the one of uterine dehiscence and rupture that is similar compared to numbers reported after classical cesarean deliveries.

/pdf/subsequent-pregnancy-outcomes-after-open-in-utero-spina-1u1yqhb7.pdf

Subsequent Pregnancy Outcomes after Open in utero Spina Bifida Repair

Intraoperative fetal bradycardia during open fetal spina bifida repair

Maternal and fetal complications following open fetal spina bifida repair – a follow up study on the first 220 cases

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