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Contains fulltext : 307208.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 307375.pdf (Publisher’s version ) (Open Access)

Radboud University, 12 april 2023, Promotores : Ulrich, D.J.O., Selles, R.W., Hovius, S.E.R. Co-promotor : Heijden, E.P.A. van der, Contains fulltext : 291361.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext, BACKGROUND: Extracorporeal perfusion (ECP) is a promising technique for prolonged tissue preservation, but might have side effects. For instance, increased radical oxygen species or capillary endothelial damage. OBJECTIVE: To assess ultra-morphological muscle damage during 36-hour ECP of porcine musculocutaneous flaps, hypothesizing that it would delay the onset of damage compared to static cold storage (SCS). METHODS: Bilateral flaps were retrieved from three Dutch Landrace pigs. Three flaps were preserved for 36 hours by hypothermic storage 4-6°C (control group) and three flaps by ECP with cooled University of Wisconsin solution. Muscle biopsies were taken at 0 h, 12 h and 36 h and assessed with transmission electron microscopy. RESULTS: Muscle architecture was best preserved by ECP, with a delayed onset and decreased severity of muscle damage. After 36 hours, damage was two-fold lower in ECP-flaps compared to SCS-flaps. Myofibril architecture was best preserved. Mitochondria were greatly preserved with swelling being the most prominent feature. Capillaries were moderately but differently damaged during ECP, with focal endothelial thinning as opposed to luminal obstruction in SCS-preserved flaps. CONCLUSIONS: This experiment described favourable cellular preservation of skeletal muscle flaps during ECP compared to SCS. Results showed less severe ultra-morphological damage and a later onset of damage.

01 februari 2023, Item does not contain fulltext, PURPOSE: This systematic review aims to provide an overview of the literature on the effect of hyperbaric oxygen therapy (HBOT) on symptoms of local late radiation toxicity (LRT) in patients treated for breast cancer. METHODS: A systematic search was performed in September 2021. All studies with a sample size of ≥10 patients reporting the effect of HBOT for symptoms of LRT after radiotherapy of the breast and/or chest wall were included. The ROBINS-I tool was used for critical appraisal of methodological quality. The toxicity outcomes pain, fibrosis, lymphedema, necrosis/skin problems, arm and shoulder mobility, and breast and arm symptoms were evaluated. RESULTS: Nine studies concerning a total of 1308 patients were included in this review. Except for one study, sample sizes were small. Most studies had inadequate methodology with a substantial risk of bias. Post-HBOT, a significant reduction of pain was observed in 4/5 studies, of fibrosis in 1/2 studies, and of lymphedema of the breast and/or arm in 4/7 studies. Skin problems of the breast were significantly reduced in 1/2 studies, arm- and shoulder mobility significantly improved in 2/2 studies, and breast- and arm symptoms were significantly reduced in one study. CONCLUSION: This systematic review indicates that HBOT might be useful for reducing symptoms of LRT in breast cancer patients, however evidence is limited. A randomized controlled trial in a larger cohort of patients including a combination of patient- and clinician-reported outcome measures would be valuable to assess the effect of HBOT on symptoms of LRT.

Contains fulltext : 295275.pdf (Publisher’s version ) (Open Access)

01 september 2023, Item does not contain fulltext, BACKGROUND: Upper blepharoplasty is the most popular facial cosmetic surgery. Although there are a variety of reasons to undergo this procedure, all patients expect an optimal cosmetic result. However, little is known about the factors that influence satisfaction with treatment outcome. OBJECTIVES: We assessed to what extent patient characteristics, clinician-rated and postsurgical outcome measures, and patient-reported satisfaction with facial appearance and quality-of-life are associated with patient-reported satisfaction with treatment outcome after a primary upper blepharoplasty. METHODS: This study was performed in 583 patients with an upper blepharoplasty between 2016 and 2021. The primary outcome was satisfaction with treatment outcome 6 months postoperatively using the FACE-Q. Determinants were baseline patient characteristics (demographics), preoperative and postoperative clinician-rated and surgical outcome measures, and preoperative and postoperative FACE-Q appearance and quality-of-life scales. Hierarchical linear regression analysis was used to determine how much of the variance in satisfaction with outcome could be explained by these groups of determinants. RESULTS: A total of 63% of the variance could be explained by the five groups of determinants of which 8% was explained by the baseline patient characteristics and clinician-rated and patient-reported outcomes together, another 8% by the postoperative clinician-rated outcomes, and the remaining 47% by the postoperative patient-reported outcomes. CONCLUSIONS: Patient characteristics, clinician-rated outcome measures, and baseline FACE-Q appearance and quality-of-life scores were of limited value in explaining satisfaction with treatment outcome. However, the postoperative FACE-Q appearance scale and the decision to undergo a blepharoplasty were strongly associated with satisfaction with treatment outcome.

Contains fulltext : 300051.pdf (Publisher’s version ) (Open Access), In outcome measures, item response theory (IRT) validation can deliver interval-scaled high-quality measurement that can be harnessed using computerized adaptive tests (CATs) to pose fewer questions to patients. We aimed to develop a CAT by developing an IRT model for the Patient Evaluation Measure (PEM) for patients undergoing cubital tunnel syndrome (CuTS) surgery. Nine hundred and seventy-nine completed PEM responses of patients with CuTS in the United Kingdom Hand Registry were used to develop and calibrate the CAT. Its performance was then evaluated in a simulated cohort of 1000 patients. The CAT reduced the original PEM length from ten to a median of two questions (range two to four), while preserving a high level of precision (median standard error of measurement of 0.27). The mean error between the CAT score and full-length score was 0.08%. A Bland-Altman analysis showed good agreement with no signs of bias. The CAT version of the PEM can substantially reduce patient burden while enhancing construct validity by harnessing IRT for patients undergoing CuTS surgery., 01 november 2023

Contains fulltext : 243843.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 247460.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 288596.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 251704.pdf (Publisher’s version ) (Open Access)

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Radboud University, 22 november 2022, Promotor : Ulrich, D.J.O. Co-promotores : Slater, N.J., Hummelink, S.L.M., Contains fulltext : 283479.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: In breast reconstruction operations, surgical wound dehiscence is a serious complication that generates a significant burden on patients and health care systems. There are indications that postoperative treatment with closed-incision negative-pressure therapy has been associated with reduced wound dehiscence rates. This randomized clinical trial examines the effect of closed-incision negative-pressure application on abdominal donor-site surgical wound dehiscence in low- and high-risk patients undergoing breast reconstruction with a deep inferior epigastric perforator flap. METHODS: Eighty eligible women, stratified as low- or high-risk patients, were included and were randomized for treatment with either closed-incision negative-pressure or adhesive strips by drawing sealed, opaque envelopes. All surgeons were kept blinded for allocation. Primary outcomes were surgical wound dehiscence and surgical-site infection at the abdominal donor site on follow-up after 12 weeks. Secondary outcomes were seroma and hematoma formation. Five patients were excluded from the study because of insufficient exposure to the study treatment ( n = 4) or major protocol deviation ( n = 1). RESULTS: A total of 75 women, low-risk ( n = 38) and high-risk ( n = 37), received either closed-incision negative-pressure ( n = 36) or adhesive strips ( n = 39). Patients' demographics did not differ significantly. Donor-site surgical wound dehiscence occurred in 23 patients; the absolute risk reduction was statistically significant (21.6 percent; 95 percent CI, 1.5 to 41.7 percent). No statistically significant differences were found in surgical-site infection or secondary outcomes. CONCLUSION: In this randomized clinical trial, postoperative treatment with closed-incision negative-pressure therapy decreased the incidence of surgical wound dehiscence at the abdominal donor site in low- and high-risk deep inferior epigastric perforator flap breast reconstruction patients. CLINICAL QUESTION

Item does not contain fulltext, BACKGROUND: Mechanical evacuation of capillary thrombi in free flaps is difficult, and often requires thrombolytic therapy. Utilizing machine perfusion systems, the possibility rises to salvage free flaps ex vivo by administering high doses of thrombolytic agents. The primary aim of this pilot study in a porcine model is to investigate the feasibility of ex vivo thrombolysis using an extracorporeal perfusion machine. METHODS: A model of stasis-induced thrombosis was used in 12 free rectus abdominis flaps harvested from six Dutch Landrace pigs. Compromised flaps were ex vivo perfused with University of Wisconsin preservation solution and treated according to the following study groups: (1) 1 mg of tissue plasminogen activator (t-PA) as additive, (2) 3 mg of t-PA as an additive, and (3) no thrombolytic additive. Microcirculation was assessed using near-infrared fluorescence angiography. RESULTS: Pedicled abdominal flaps were created and thrombus formation was successfully induced. Eleven abdominal flaps were perfused using the modified heart-lung machine setup. Near-infrared fluorescence angiography showed delayed or no filling was noted in the control group. In comparison, the flaps which were perfused with 1 mg t-PA or 3 mg t-PA as additive showed increased fluorescence intensity curves. CONCLUSION: This pilot study in a porcine model presents a reliable and reproductive stasis-induced thrombosis model in free flaps. By adding t-PA to a custom-made extracorporeal perfusion system, the indocyanine green fluorescence intensity curves increased of all flaps that were perfused with different dosages of t-PA as additives, indicating restoration of capillary pressure and microcirculatory inflow.

Contains fulltext : 251695.pdf (Publisher’s version ) (Open Access), BACKGROUND: Vascularized lymph node transfer (VLNT) has become an increasingly popular technique for treating lymphedema. However, although many studies have been performed, its efficacy in increasing patients' quality of life (QoL) and reducing lymphedema in the affected body part has remained controversial. In the present systematic review, we summarized the evidence for VLNT for treating breast cancer-related lymphedema. METHODS: The MEDLINE, Embase, and Cochrane Central databases were searched for studies of patients with breast cancer-related lymphedema who had received VLNT. The study methods were assessed using the MINORS (methodologic index for nonrandomized studies) tool. The primary outcomes were the change in volume difference between the arms and QoL. The secondary outcomes were skin infection, complications, and discontinuation of compression garment use. RESULTS: A total of 17 studies were included for qualitative synthesis and 8 for meta-analysis. The average reduction rate between the healthy and affected arms in the studies included in the meta-analysis was 40.31%. Five studies had evaluated QoL, and all five studies had reported that QoL was significantly increased. Eight studies had evaluated skin infections, of which three had reported the annual infection rates before and after surgery. In these studies, infection rate had decreased significantly. Three studies had described usage of compression garments. When the patients were pooled, 27 of 60 were able to discontinue use of the compression garment. The donor and recipient complication rates were 12.1% and 7.3%, respectively. CONCLUSIONS: The current evidence indicates that VLNT can improve the volume differences between the arms in patients with unilateral lymphedema by ∼40%. In addition, although determined from a few studies, it is likely that VLNT has a positive effect on patients' QoL, the number of skin infections, and compression garment usage and coincided with a low complication rate.

Item does not contain fulltext, BACKGROUND: There is a risk for thrombotic complications (2 to 5 percent) associated with microsurgical reconstruction. Current thrombolytic therapy has a salvage rate between 60 and 70 percent, but it is afflicted by bleeding complications (2 to 6 percent). The use of machine perfusion for delivering thrombolytic agents is a new method that could potentially reduce these complications. In this article, the authors compared flap salvage outcomes comparing machine thrombolysis versus a manual flush with tissue plasminogen activator. METHODS: Sixteen bilateral flaps (12 × 9 cm) were dissected from eight female Dutch Landrace pigs (70 kg). Thrombosis was induced in free rectus abdominis flaps by clamping the pedicle's veins for 2 hours. Flaps were either thrombolysed with 2 mg tissue plasminogen activator (1 mg/ml) during 2 hours of machine perfusion (perfusion group; n = 8) or injected intraarterially (manual group; n = 8) before replantation. Near-infrared fluorescence angiography was used to confirm thrombus formation and to assess tissue perfusion; muscle biopsy specimens were analyzed for ischemia/reperfusion injury directly after thrombolysis and 15 hours after replantation. RESULTS: A higher incidence of secondary thrombosis was seen in the manual group compared to the perfusion group ( n = 6 versus n = 0, respectively; p < 0.001), resulting in two complete flap failures. Fifteen hours after replantation, mean fluorescence intensities were 13.0 (95 percent CI, 10.1 to 15.8) and 24.6 (95 percent CI, 22.0 to 27.2) in the perfusion and manual group, respectively ( p < 0.001), and mean muscle injury scores were comparable, measuring 7.5 ± 1.5. CONCLUSION: Two hours of machine thrombolysis of compromised flaps in a porcine model showed higher salvage rates compared to a manual injection with tissue plasminogen activator and reduced the incidence of secondary thrombosis. CLINICAL RELEVANCE STATEMENT: Using machine perfusion systems for ex vivo thrombolysis provides th

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Item does not contain fulltext, PURPOSE: The purpose of this research was to explore women's experiences after breast surgery with scar characteristics and symptoms, and its impact on their health-related quality of life (HRQOL). MATERIAL AND METHODS: A qualitative study using semi-structured face-to-face interviews was conducted among women following prophylactic, oncologic, or reconstructive breast surgery in the Netherlands. A directed content analysis was performed using guiding themes. Themes were "physical and sensory symptoms," "impact of scar symptoms," "personal factors," "impact of scar interventions," and "change over time." RESULTS: The study population consisted of 26 women after breast surgery. Women experienced a wide range of symptoms like adherence, stiffness, pain, and uncomfortable sensations. Scar characteristics as visibility, location, texture, and size, influenced satisfaction with their appearance. The impact of scar symptoms is reflected in physical, social, emotional, and cognitive functioning, thereby affecting HRQOL. The experienced impact on HRQOL depended on several factors, like personal factors as the degree of acceptance and environmental factors like social support. CONCLUSION: Women can experience a diversity of scar characteristics and symptoms, which play a central role in the perceived impact on HRQOL. Since scarring can have a considerable impact on HRQOL, scarring after prophylactic, oncologic and reconstructive breast surgery should be given more attention in clinical practice and research. IMPLICATIONS FOR CANCER SURVIVORS: Considering scarring as a common late effect after breast surgery and understanding the variety of experiences, which could impact HRQOL of women, can be beneficial in sufficient information provision, expectation management, and informed decision making.

Item does not contain fulltext, OBJECTIVE: To preoperatively plan skin incision in the case of the first Dutch bilateral hand-arm transplantation. BACKGROUND: A bilateral hand-arm transplantation has been performed for the first time in the Netherlands in 2019. In the context of preparation for this surgical procedure, the optimal patient-specific skin flap was determined. Skin flaps should be properly matched between donor and recipient to ensure sufficient tissue for the approximation of skin over the tendon anastomosis, adequate distal tip perfusion, and esthetics. METHODS: Preoperatively, stereophotogrammetry was obtained from the upper extremities of the patient and a volunteer with similar body physique. Skin flap dimensions were determined for each extremity, which resulted in patient-specific incision patterns. Combining this digital information yielded practical skin incision guides for both the donor and acceptor arms. Finally, the computer-aided designs were 3D printed. RESULTS: The 3D prints were convenient to utilize in both shaping the donor flaps as in preparing the acceptor extremities, taking only a few seconds during precious ischemia time. There was sufficient skin flap perfusion, and the wound-healing followed an uncomplicated course. No corrections were made to the initial skin incisions. CONCLUSIONS: Three-dimensional printed templates were successfully utilized in the first Dutch bilateral hand-arm transplantation. We believe its usage increased time efficiency, improved the match of skin flaps in donor and recipient arms, and allowed us to control the amount of skin surplus without skin flap tip necrosis. In these procedures where time is of the essence, we believe preoperative planning is imperative for its success.

Contains fulltext : 240616.pdf (Publisher’s version ) (Open Access), INTRODUCTION: In large full-thickness skin defects, donor site morbidity limits the available thickness and surface of skin autografts and therefore only split-thickness skin grafts are possible for reconstruction. Dermal equivalents can be added to these split-thickness grafts to acquire an anatomically better skin reconstruction. Glyaderm is a human derived, acellular dermis and up until now has only been used in a two-staged procedure. This report describes results of a case series using Glyaderm and split-thickness skin grafts in a single-staged procedure. METHODS: Glyaderm was introduced in 2017 in Radboudumc (Nijmegen, The Netherlands). Glyaderm and autologous split-skin grafts were simultaneously applied to the wounds. In cases with large wound surfaces or wounds covering highly mobile areas, negative pressure wound therapy was additionally applied. The first ten cases were followed with regular intervals post-operatively, assessing graft take, scar appearance, post-operative wound problems and re-interventions. RESULTS: Patients were aged 3 weeks to 76 years-old. Treated skin surface varied from 1-16% total body surface. Wounds resulted from trauma (n = 4), burns (n = 4) or soft tissue infections (n = 2). Follow-up varied from 4 months to 1.5 years. No complications occurred after surgery. Average take rate was 98%. Two patients had a later re-intervention to further improve the aesthetic appearance of the scarred area. CONCLUSION: Our first results with the application of Glyaderm in a single-staged procedure provided good healing, graft take and scar appearance. Glyaderm was found a suitable dermal substitute in the treatment of full thickness wounds.

Contains fulltext : 237694.pdf (Publisher’s version ) (Open Access), The aim of the current study is to assess the biological performance of self-healing hydrogels based on calcium phosphate (CaP) nanoparticles and bisphosphonate (BP) conjugated hyaluronan (HA) in a critical size segmental femoral bone defect model in rats. Additionally, these hydrogels are loaded with bone morphogenetic protein 2 (BMP-2) and their performance is compared in healthy and osteoporotic bone conditions. Treatment groups comprise internal plate fixation and placement of a PTFE tube containing hydrogel (HA(BP) -CaP) or hydrogel loaded with BMP-2 in two dosages (HA(BP) -CaP-lowBMP2 or HA(BP) -CaP-highBMP2). Twelve weeks after bone defect surgery, bone formation is analyzed by X-ray examination, micro-CT analysis, and histomorphometry. The data show that critical size, segmental femoral bone defects cannot be healed with HA(BP) -CaP gel alone. Loading of the HA(BP) -CaP gel with low dose BMP-2 significantly improve bone formation and resulted in defect bridging in 100% of the defects. Alternatively, high dose BMP-2 loading of the HA(BP) -CaP gel does not improve bone formation within the defect area, but leads to excessive bone formation outside the defect area. Bone defect healing is not affected by osteoporotic bone conditions.

Radboud University, 10 september 2021, Promotores : Hovius, S.E.R., Ulrich, D.J.O. Co-promotor : Nijhuis, T.H.J., Contains fulltext : 235912.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: During a deep inferior epigastric perforator (DIEP) flap harvest, the identification and localization of the epigastric arteries and its perforators are crucial. Holographic augmented reality is an innovative technique that can be used to visualize this patient-specific anatomy extracted from a computed tomographic scan directly on the patient. This study describes an innovative workflow to achieve this. METHODS: A software application for the Microsoft HoloLens was developed to visualize the anatomy as a hologram. By using abdominal nevi as natural landmarks, the anatomy hologram is registered to the patient. To ensure that the anatomy hologram remains correctly positioned when the patient or the user moves, real-time patient tracking is obtained with a quick response marker attached to the patient. RESULTS: Holographic augmented reality can be used to visualize the epigastric arteries and its perforators in preparation for a deep inferior epigastric perforator flap harvest. CONCLUSIONS: Potentially, this workflow can be used visualize the vessels intraoperatively. Furthermore, this workflow is intuitive to use and could be applied for other flaps or other types of surgery.

Radboud University, 10 september 2021, Promotores : Ulrich, D.J.O., Hovius, S.E.R., Contains fulltext : 235909.pdf (Publisher’s version ) (Open Access)

Radboud University, 24 september 2021, Promotor : Ulrich, D.J.O. Co-promotores : Hummelink, S.L.M., Schreinemachers, M.J.M., Contains fulltext : 235923.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 237190.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 231785.pdf (Publisher’s version ) (Open Access), The current standard for composite tissue preservation is static cold storage (SCS) and is limited to 6 h until irreversible muscle damage occurs. Extracorporeal perfusion (ECP) is a promising technique for prolonged preservation, however, functional results have been scarcely researched. This article assessed neuromuscular function and compared results to histological alterations to predict muscle damage after ECP. Forelimbs of twelve Dutch landrace pigs were amputated and preserved by 4 h SCS at 4-6 °C (n = 6) or 18 h mid-thermic ECP with University of Wisconsin solution (n = 6). Limbs were replanted and observed for 12 h. Sham surgery was performed on contralateral forelimbs (n = 12). Histology analysis scored four subgroups representing different alterations (higher score equals more damage). Muscle contraction after median nerve stimulation was comparable between ECP, SCS, and sham limbs (P = 0.193). Histology scores were higher in ECP limbs compared to SCS limbs (4.8 vs. 1.5, P = 0.013). This was mainly based on more oedema in these limbs. In-vivo muscle contraction was well preserved after 18 h ECP compared to short SCS, although histology seemed inferior in this group. Histology, therefore, did not correlate to muscle function at 12 h after replantation. This leads to the question whether histology or neuromuscular function is the best predictor for transplant success.

Radboud University, 12 november 2021, Promotores : Hovius, S.E.R., Ulrich, D.J.O., Selles, R.W., Contains fulltext : 239217.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext, INTRODUCTION: Radiotherapy reduces the risk of locoregional recurrence of breast cancer. As a side-effect, tissue can become hypocellular, hypovascular, and hypoxic and late radiation tissue injury can develop months or years later. Radiotherapy increases the risk of complications following secondary breast reconstruction. Hyperbaric oxygen treatment (HBOT) improves oxygenation of irradiated tissue and induces neovascularisation. This study evaluated whether the incidence of complications following secondary breast reconstruction after radiotherapy is decreased with perioperative HBOT. METHODS: In this retrospective case-control chart review study, patients who underwent perioperative HBOT (n = 15) were compared to lifestyle-matched (n = 15) and radiation damage-matched (n = 15) patients who underwent secondary breast reconstruction without HBOT. RESULTS: The HBOT group had significantly more severe radiation damage of the breast than the lifestyle- and radiation-damage-matched control groups (scoring grade 1-4, mean 3.55 versus 1.75 and 2.89 respectively, P = 0.001). Patients underwent on average 33 sessions of HBOT (18 sessions preoperatively and 15 sessions postoperatively). There was no significant difference in the incidence of postoperative complications between the HBOT group, lifestyle-matched group and radiation damage-matched group. Logistic regression analysis showed a lower risk of postoperative complications in patients who underwent HBOT. CONCLUSIONS: Although the HBOT group had more radiation damage than the control groups, the incidence of postoperative complications was not significantly different. This implied a beneficial effect of HBOT, which was supported by the logistic regression analysis. Definitive conclusions cannot be drawn due to the small sample size. Future research is justified, preferably a large randomised controlled trial.

Contains fulltext : 230100.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 231787.pdf (publisher's version ) (Open Access), The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration; however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of pre-existing vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.