Incompatible Donor Research Articles

Local FK506 drug delivery enhances nerve regeneration through fresh, unprocessed peripheral nerve allografts

ObjectiveNerve allografts offer many advantages in the reconstruction of peripheral nerve gaps: they retain their native microstructure, contain pro-regenerative Schwann cells, are widely available, and avoid donor site morbidity. Unfortunately, clinical use of nerve allografts is limited by the need for systemic immunosuppression and its adverse effects. To eliminate the toxicity of the systemic immunosuppressant FK506, we developed a local FK506 drug delivery system (DDS) to provide drug release over 28 days. The study objective was to investigate if the local FK506 DDS enhances nerve regeneration in a rodent model of nerve gap defect reconstruction with immunologically-disparate nerve allografts. MethodsIn male Lewis rats, a common peroneal nerve gap defect was reconstructed with either a 20 mm nerve isograft from a donor Lewis rat or a 20 mm fresh, unprocessed nerve allograft from an immunologically incompatible donor ACI rat. After 4 weeks of survival, nerve regeneration was evaluated using retrograde neuronal labelling, quantitative histomorphometry, and serum cytokine profile. ResultsTreatment with both systemic FK506 and the local FK506 DDS significantly improved motor and sensory neuronal regeneration, as well as histomorphometric indices including myelinated axon number. Rats with nerve allografts treated with either systemic or local FK506 had significantly reduced serum concentrations of the pro-inflammatory cytokine IL-12 compared to untreated vehicle control rats with nerve allografts. Serum FK506 levels were undetectable in rats with local FK506 DDS. InterpretationThe local FK506 DDS improved motor and sensory nerve regeneration through fresh nerve allografts to a level equal to that of either systemic FK506 or nerve isografting. This treatment may be clinically translatable in peripheral nerve reconstruction or vascularized composite allotransplantation.

A phase 2 trial of GVHD prophylaxis with PTCy, sirolimus, and MMF after peripheral blood haploidentical transplantation

AbstractThe introduction of posttransplant cyclophosphamide (PTCy) made performing allogeneic hematopoietic cell transplantation (HCT) from HLA haplotype–incompatible donors possible. In a setting of PTCy and tacrolimus/mycophenolate mofetil (MMF) as a graft-versus-host disease (GVHD) prophylaxis, a peripheral blood (PB) graft source as compared with bone marrow reduces the relapse rate but increases acute GVHD (aGVHD) and chronic GVHD (cGVHD). This phase 2 trial assessed sirolimus and MMF efficacy following PTCy as a GVHD prophylaxis after PB haploidentical HCT (haplo-HCT). With 32 evaluable patients (≥18 years) enrolled, this study had 90% power to demonstrate a reduction in 100-day grade II-IV aGVHD to 20% from the historical benchmark of 40% after haplo-HCT using PTCy/tacrolimus/MMF. At a median follow-up of 16.1 months, the primary end point of the trial was met with a day-100 grade II-IV aGVHD cumulative incidence of 18.8% (95% confidence interval [CI], 7.5% to 34.0%). There were no graft-failure events and the 1-year probability of National Institutes of Health (NIH) moderate/severe cGVHD was 18.8% (95% CI, 7.4% to 34.0%), nonrelapse mortality was 18.8% (95% CI, 7.4% to 34.0%), relapse was 22.2% (95% CI, 9.6% to 38.2%), disease-free survival was 59.0% (95% CI, 44.1% to 79.0%), GVHD-free relapse-free survival was 49.6% (95% CI, 34.9% to 70.5%), and overall survival was 71.7% (95% CI, 57.7% to 89.2%) for the entire cohort. These data demonstrate that GVHD prophylaxis with sirolimus/MMF following PTCy effectively prevents grade II-IV aGVHD after PB haplo-HCT, warranting prospective comparison of sirolimus vs tacrolimus in combination with MMF following PTCy as GVHD prophylaxis after PB HCT. This trial was registered at www.clinicaltrials.gov as #NCT03018223.

The top‐trading cycles and chains solution for kidney exchange with immunosuppressants

AbstractIn kidney transplantation, immunosuppressants are being used to relax all immunological constraints, allowing patients to receive transplants from biologically incompatible donors. We propose an efficient way of using immunosuppressants in combination with a kidney exchange program. We introduce the top‐trading cycles and chains solution, a modification of the top‐trading cycles rule for the standard kidney exchange problem, and investigate its properties.

HLA Class II Positivity by Lysate Crossmatch in Renal Transplant Scenario-Dangerous if Ignored!!!

The detection of antibodies before transplantation is an important step in assessment of patient immunological risk and exclusion of incompatible donors. Many centers have now implemented donor-specific antibody (DSA) along with complement-dependent cytotoxicity crossmatch (CDC XM) for renal transplant cases. A 34-year-old male with end-stage kidney disease was referred for an ABO-compatible transplant from his mother. The CDC XM done 30 days before transplant was negative. DSA XM was negative for Class I (median fluorescence intensity [MFI] 189) and positive for Class II (MFI 1671). Since CDC and DSA Class I were negative, the nephrologists went ahead with the transplantation. On day 6 posttransplant, serum creatinine showed a rising trend (up to 2.13 mg/dl), and therefore, renal biopsy was done which showed mild acute tubular necrosis with positive C4d staining. DSA XM performed on day 15 posttransplant showed negative Class I (MFI 148) and positive Class II (MFI 9987) confirming antibody-mediated rejection (AMR). The patient was started on steroids, and intravenous immunoglobulin and serial plasma exchanges were performed. Then, DSA Class II levels came down to 1602. DSA levels have been monitored periodically and Class II MFI values have been ranging from 2000 to 4000. The patient is maintained on routine immunosuppression, and a graft is intact with serum creatinine level between 1.7 and 1.8 mg/dl 8 months posttransplant. DSA-isolated Class II positivity in renal transplant recipients correlates strongly with AMR and should be considered clinically significant.

Abstract 13046: Treatment of Highly Sensitized Patients Before Heart Transplant Associated With Long-term Post-transplant Benefit

Introduction: Highly sensitized patients awaiting heart transplantation (HTx) are disadvantaged by a narrow donor pool due to incompatible potential donors. Desensitization therapy has been demonstrated to be effective in lowering antibodies and thereby enlarging the donor pool. By desensitization, the calculated panel reactive antibody (cPRA) has been reported to decrease and result in a shorter waitlist time. It has not been established whether desensitization before transplant can have impact after HTx outcomes. Methods: Between 2010 and 2015, we assessed 34 patients awaiting HTx who had a PRA >50% and underwent desensitization therapy. Desensitization therapy included combinations of IVIG, rituximab, plasmapheresis, and bortezomib. These patients who underwent HTx were then assessed for outcomes, which included 5-year survival, freedom from cardiac allograft vasculopathy (CAV), freedom from non-fatal major adverse cardiac events (NF-MACE), and freedom from donor specific antibody (DSA) development and 1-year freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody mediated rejection (AMR)). Patients who underwent desensitization were compared to a similar group of patients with PRA >50% who did not undergo desensitization and underwent HTx. Results: Patients who underwent desensitization compared to those who did not had significantly greater freedom from 5-year development of CAV (94.1 vs 78.8%, p=0.039). There was no significant difference in 5-year survival, 5-year freedom from NF-MACE or DSA development, and 1-year freedom from ATR, ACR, AMR. Conclusions: Desensitization in highly sensitized patients awaiting HTx appears to have long ranging effects to modulate the immune system after HTx, resulting in less development of CAV. Further investigation should be pursued to understand the mechanism of this intervention.

Deceased donors as nondirected donors in kidney paired donation.

As proof of concept, we simulate a revised kidney allocation system that includes deceased donor (DD) kidneys as chain-initiating kidneys (DD-CIK) in a kidney paired donation pool (KPDP), and estimate potential increases in number of transplants. We consider chains of length 2 in which the DD-CIK gives to a candidate in the KPDP, and that candidate's incompatible donor donates to theDD waitlist. In simulations, we vary initial pool size, arrival rates of candidate/donor pairs and (living) nondirected donors (NDDs), and delay time from entry to the KPDP until a candidate is eligible to receive a DD-CIK. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Kidney Donation, and the actual DDs from the Scientific Registry of Transplant Recipients (SRTR) data, simulations extend over 2years. With an initial pool of 400, respective candidate and NDD arrival rates of 2 per day and 3 per month, and delay times for access to DD-CIK of 6months or less, including DD-CIKs increases the number of transplants by at least 447 over 2years, and greatly reduces waiting times of KPDP candidates. Potential effects on waitlist candidates are discussed as are policy and ethical issues.

Fairness models for multi-agent kidney exchange programmes

Nowadays there are several countries running independent kidney exchange programmes (KEPs). These programmes allow a patient with kidney failure, having a willing healthy but incompatible donor, to receive a transplant from a similar pair where the donor is compatible with him. Since in general larger patient-donor pools allow for more patients to be matched, this prompts independent programmes (agents) to merge their pools and collaborate in order to increase the overall number of transplants. Such collaboration does however raise a problem: how to assign transplants to agents so that there is a balance between the contribution each agent brings to the merged pool and the benefit it gets from the collaboration.In this paper we propose a new Integer Programming model for multi-agent kidney exchange programmes (mKEPs). It considers the possible existence of multiple optimal solutions in each matching period of a KEP and, in consecutive matching periods, selects the optimal solution among the set of alternative ones in such a way that in the long-term the benefit each agent gets from participating in the mKEP is balanced accordingly to a given criterion. This is done by use of a memory mechanism. Extensive computational tests show the benefit of mKEPs, when compared to independent KEPs, in terms of potential increase in the number of transplants. Furthermore, they show that, under different policies, the number of additional transplants each agent receives can vary significantly. More importantly, results show that the proposed methodology consistently obtains more stable results than methodologies that do not use memory.

Crossing borders to facilitate live donor kidney transplantation: the Czech-Austrian kidney paired donation program - a retrospective study.

Kidney paired donation (KPD) is a valuable tool to overcome immunological barriers in living donor transplantation. While small national registries encounter difficulties in finding compatible matches, multi-national KPD may be a useful strategy to facilitate transplantation. The Czech (Prague) and Austrian (Vienna) KPD programs, both initiated in 2011, were merged in 2015. A bi-national algorithm allowed for ABO- and low-level HLA antibody-incompatible exchanges, including the option of altruistic donor-initiated domino chains. Between 2011 and 2019, 222 recipients and their incompatible donors were registered. Of those, 95.7% (Prague) and 67.9% (Vienna) entered into KPD registries, and 81 patients received a transplant (95% 3-year graft survival). Inclusion of ABO-incompatible pairs in the Czech program contributed to higher KPD transplant rates (42.6% vs. 23.6% in Austria). After 2015 (11 bi-national match runs), the median pool size increased to 18 pairs, yielding 33 transplants (8 via cross-border exchanges). While matching rates doubled in Austria (from 9.1% to 18.8%), rates decreased in the Czech program, partly due to implementation of more stringent HLA antibody thresholds. Our results demonstrate the feasibility of merging small national KPD programs to increase pool sizes and may encourage the implementation of multi-national registries to expand the full potential of KPD.

Kidney exchange with immunosuppressants

Recent developments in immunosuppressive protocols have enabled patients to receive kidney transplants from biologically incompatible donors. We propose to use immunosuppressants as a part of kidney exchange program. We introduce the “pairwise cycles and chains (PCC)” solution and show that it is Pareto efficient, monotonic, and maximizes the number of compatible transplants and the total number of transplants at the same time among all monotonic matchings.

Outcome of ABO Blood Type–Incompatible Living-Related Donor Kidney Transplantation Under a Contemporary Immunosuppression Strategy in Japan

BackgroundBecause of the serious donor shortage in Japan, there is an increasing need for ABO blood type–incompatible kidney transplantation (ABOi-KT) in living-related donor kidney transplantation. We evaluated the outcomes of ABOi-KT performed at our hospitals using a contemporary immunosuppression strategy with low-dose rituximab. Patients and MethodsBetween June 2006 and April 2019, 107 patients underwent living-related donor kidney transplantation at our hospitals. The patients were divided into ABO-compatible (ABOc) and ABOi groups. The basic immunosuppression regimen differed between the 2 groups in the use of low-dose rituximab and therapeutic apheresis in the ABOi group. We compared graft survival, patient survival, rejection, viral infection, and posttransplant renal function between the 2 groups. ResultsOf 107 recipients, 37 (35%) underwent ABOi-KT. The 5-year graft survival rates in the ABOc and ABOi group were 91% and 100%, respectively. The Kaplan-Meier analyses showed no difference in graft survival (P = .168) or patient survival (P = .873) between the groups. Biopsy-proven rejection in the ABOc and ABOi groups was observed in 13 (19%) and 7 (19%) patients, respectively (P = .965), and viral infection was observed in 21 (30%) and 10 (27%) patients (P = .747), respectively. Renal function by estimated glomerular filtration rate from 1 week to 5 years after transplantation was similar in both groups. ConclusionsThe outcomes of ABOi-KT with low-dose rituximab were comparable with those of ABOc-KT at our hospitals. ABOi-KT with proper immunosuppression may be an option to help resolve the severe donor shortage in Japan.

Post-Heart Transplant Outcomes of Sensitized Patients Who Have Undergone Desensitization Therapy

Sensitized patients awaiting heart transplantation (HTx) are at increased risk for mortality as their waitlist time is lengthened due to incompatible donors and a subsequently narrowed donor pool. Therefore, these patients undergo desensitization therapies to lower circulating antibodies and to restore the donor pool for these patients. These patients subsequently undergo HTx; however it has not been well established as to their longer-term outcome following HTx. Between 2010 and 2014 we assessed 42 patients awaiting HTx who were sensitized (average cPRA 84%) and subsequently underwent desensitization therapy prior to HTx. These patients then underwent HTx and were followed for 5-year outcome. Endpoints post-HTx included 5-year survival, 5-year freedom from cardiac allograft vasculopathy (CAV), 5-year freedom from non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention/angioplasty, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, stroke), and 1-year freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), antibody mediated rejection (AMR)). Patients were compared to a contemporaneous group of HTx patients that did not receive desensitization therapy prior to HTx conditional to 1-year survival (n=329) for the same endpoints. Sensitized patients that received desensitization therapy prior to HTx had significantly lower freedom from AMR. There is a trend for increased freedom from NF-MACE in this desensitized group. There were no differences between the two groups in terms of survival, freedom from CAV, and freedom from ACR. Sensitized patients awaiting HTx who undergo desensitization therapy appear to have decreased freedom from first-year AMR. However, these patients appear to have comparable outcome (ie survival and CAV) at 5-years post-HTx to HTx patients that do not undergo desensitization therapy.

A Kidney Exchange Matching Application Using the Blossom and Hungarian Algorithms for Pairwise and Multiway Matching

Background/objectives: Patients of kidney failure sometimes have incompatible donors. This study proposes an application to get the best matchings based on scoring data. Methods: For pairwise matching, we created a new graph from the original scoring matrix. This graph ensures pairwise matchings. To find an optimal matching, we used the Blossom algorithm. For multiway matching, we interpreted the scoring matrix as an assignment problem. For this, we used the Hungarian algorithm. The application was created using Python, NetworkX, NumPy, and PySimpleGUI. The app uses CSV files as input. Findings: Both algorithms made for polynomial run times. Matching is fast and is guaranteed to be optimal. The application itself gets instantaneous results even for large donor-patient matrices. Application/improvement: Hospitals or organizations can use this application for their kidney matching programs. Keywords: Blossom Algorithm, Hungarian Algorithm, Kidney Failure, Donor Matching.

A current era analysis of ABO incompatible listing practice and impact on outcomes in young children requiring heart transplantation

Heart transplantation from ABO incompatible (ABOi) donors has evolved into a progressively accepted therapy in young children. We assessed the recent practice of ABOi listing impact on waitlist and post-transplant outcomes. Using the Pediatric Heart Transplant Society registry, we compared clinical presentation, waitlist parameters, and post-transplant survival of children < 2 years of age listed for ABOi vs ABO compatible (ABOc) heart transplant between January 2010 and June 2018 with sub-analysis of blood group O recipients. Among 2,039 patients, ABOi listing increased significantly with time from 49% (2010) to 72% (2017). ABOi-listed patients had lower age and body surface area, and higher proportion of congenital heart disease, mechanical ventilation, and high urgency status (all p < 0.01). Use of mechanical circulatory support was similar between groups. Of 1,288 patients reaching transplant, 239 (18.6%) received an ABOi organ (15%-40%/year). Death while waiting, removal from the waitlist, and waitlist survival were similar between groups. Time to transplant was significantly shorter for ABOi listing in blood group O patients (p < 0.02), approaching significance (p = 0.057) for all blood groups. Post-transplant survival was similar except for lower survival of patients listed ABOc but transplanted ABOi. These patients showed increasing need for mechanical circulatory support and high urgency listing while waiting. In the current era, primary listing for ABOi heart transplant has become routine for the majority of children < 2 years old, resulting in shorter waitlist time, especially in blood group O. Post-transplant survival is similar despite ABOi-listed children still showing a higher risk profile.

Maximum matchings in graphs for allocating kidney paired donation

Living donors are often incompatible with their intended recipients. Kidney paired donation matches one patient and his or her incompatible donor with another pair in the same situation for an exchange. Let patient-donor pairs be the vertices of an undirected graph G, with edges connecting reciprocally compatible vertices. A matching in G is a feasible set of paired donations. Because the lifespan of a transplant depends on the immunologic concordance of donor and recipient, we weight the edges of G and seek a maximum edge-weight matching. Unfortunately, such matchings might not have the maximum cardinality; there is a risk of an unpredictable trade-off between quality and quantity of paired donations. We prove that the number of paired donations is within a multiplicative factor of the maximum possible donations, where the factor depends on the edge weighting. We propose an edge weighting of G which guarantees that every matching with maximum weight also has maximum cardinality, and also maximizes the number of transplants for an exceptional subset of recipients, while favoring immunologic concordance. We partially generalize this result to k-way exchange and chains, and we implement our weightings using a real patient dataset from Brazil.

Impact of ABO incompatibility on outcomes after haploidentical hematopoietic stem cell transplantation for severe aplastic anemia.

The impact of ABO incompatibility on transplantation outcomes in severe aplastic anemia (SAA) patients receiving haploidentical hematopoietic stem cell transplantation (HSCT) remains controversial without published data. A total of 199 SAA patients receiving haploidentical HSCT from ABO-matched (n = 114), minor ABO-incompatible (n = 47), or major ABO-incompatible donors (n = 38) were included in this study. The median time and cumulative incidences of both myeloid and platelet engraftment in the ABO-compatible and ABO-incompatible groups were similar, and pure red cell aplasia was absent. Minor ABO incompatibility increased the rate of grade III-IV acute graft-versus-host disease (aGVHD) (ABO compatible: 6.14 ± 0.05%, minor incompatible: 19.15 ± 0.34%, and major incompatible: 10.53 ± 0.25%; P = 0.051), but did not influence the rates of grade II-IV aGVHD or chronic GVHD (cGVHD). Minor ABO-incompatibility was identified as an independent risk factor for grade III-IV aGVHD by multivariate analysis (hazard ration (HR) = 4.00 (1.48-10.80), P = 0.006). Chronic GVHD, mortality, and treatment failure were not increased in the minor ABO-incompatible group. For SAA patients receiving haploidentical HSCT, ABO compatible donors are better than ABO minor incompatible donors if several haploidentical donors are available.

Ignorance Is Almost Bliss: Near-Optimal Stochastic Matching with Few Queries

We study the stochastic matching problem with the goal of finding a maximum matching in a graph whose edges are unknown but can be accessed via queries. This is a special case of stochastic k-cycle packing, in which the problem is to find a maximum packing of cycles, each of which exists with some probability. We provide polynomial-time adaptive and nonadaptive algorithms that provably yield a near-optimal solution, using a number of edge queries that is linear in the number of vertices. We are especially interested in kidney exchange, with which pairs of patients with end-stage renal failure and their willing but incompatible donors participate in a mechanism that performs compatibility tests between patients and donors and swaps the donors of some patients so that a large number of patients receive compatible kidneys. Because of the significant cost of performing compatibility tests, currently, kidney exchange programs perform at most one compatibility test per patient. Our theoretical results applied to kidney exchange show that, by increasing the number of compatibility tests performed per patient from one to a larger constant, we effectively get the full benefit of exhaustive testing at a fraction of the cost. We show, on both generated and real data from the UNOS nationwide kidney exchange, that even a small number of nonadaptive edge queries per vertex results in large gains in expected successful matches.

ABO incompatible live donor renal transplant. Study of 48 patients after desensitization

BackgroundUntil recently, ABO-incompatible living donor kidney transplantation was regarded as an absolute contraindication. However, this kind of kidney transplantation has been used in the last years, with good results. Objetive0ur objetive is to show the results obtained with this technique in our hospital. MethodsForty-eight patients with a mean age of 50,9±10,9 years were included. Follow-up 44,6±30,9 months. Conditioning: rituximab 375mg/m², tacrolimus, mycophenolate mofetil or mycophenolate sodium, prednisone, plasmapheresis/immunoadsorption and intravenous immunoglobulin. Accepted IgG and IgM titers for transplantation ≤ 1:8. ResultsPreprocess IgG titer 1:124±1:40, IgM titer 1:77±1:55. After 6±3 sessions, IgG decreased to <1:8 in 47 patients and to <1:16 in one. IgM was < 1:/8 in all cases. Twenty-five patients (50 %) presented hematoma, reintervention in 7 (14.6 %); 29 (60 %) required transfusion. Acute rejection occurred in 5 cases (8.7 % at 5 th year). CMV infection 9 (19,7 % at 5th year), BK viremia 5 (12.4 % at 5th year), post-transplant diabetes in 10 (23.4 % at 5th year), and lymphocele in 3 (6,4 % at 5th year). Patient survival was 97 % at 5th year and graft survival 95,7 % at 1st and 93 % at 5th year. Causes of graft loss: thrombosis (n=1) and mixed rejection (n=1) and death (n=2). Serum creatinine levels were 1.43±0.5mg/dl at 1st and 3rd year and 1,3±0,3mg/dl at 5th year. Proteinuria was 0.2±0.2g/24h at 1st and 5th year. ConclusionsABO incompatible living donor kidney transplantation after conditioning with rituximab, plasmapheresis/immunoadsorption and immunoglobulins is a valid option offering excellent outcomes.as survival and acute rejections without increasing infectious complications. An increased tendency towards postoperative bleeding is observed.

Pairwise Kidney Exchange over the Blood Group Barrier

AbstractAdvances in medical technology have made kidney transplants over the blood group barrier feasible. This article investigates how such technology should be implemented when designing pairwise kidney exchange programs. The possibility to receive a kidney transplant from a blood group incompatible donor motivates an extension of the preference domain, allowing patients to distinguish between compatible donors and half-compatible donors (i.e. blood group incompatible donors that only become compatible after undergoing an immunosuppressive treatment). It is demonstrated that the number of transplants can be substantially increased by providing an incentive for patients with half-compatible donors to participate in kidney exchange programs. The results also suggest that the technology is beneficial for patient groups that are traditionally disadvantaged in kidney exchange programs (e.g. blood group O patients). The positive effect of allowing transplants over the blood group barrier is larger than the corresponding effects of including altruistic patient–donor pairs or of allowing three-way exchanges in addition to pairwise exchanges.

Matching Kidneys with Priority in Kidney Exchange Programs

Kidney exchanges were developed to match kidney failure patients with willing but incompatible donors to other donor-patient pairs. Finding a match in a large candidate pool can be modeled as an integer program. However, these exchanges accumulate participants with characteristics that increase the difficulty of finding a match and, therefore, increase patients' waiting time. Therefore, we sought to fine-tune the formulation of the integer program by more accurately assigning priorities to patients based on their difficulty of matching. We provide a detailed formulation of prioritized kidney exchange and propose a novel prioritization algorithm. Our approach takes advantage of the global knowledge of the donor-patient compatibility within a pool of pairs and calculates an iterative, paired match power (iPMP) to represent the donor-patient pairs' abilities to match. Monte Carlo simulation shows that an algorithm using the iPMP reduces the waiting time more than using paired match power (PMP) for the difficult-to-match pairs with hazard ratios of 1.3480 and 1.1100, respectively. Thus, the iPMP may be a more accurate assessment of the difficulty of matching a pair in a pool than PMP is, and its use may improve matching algorithms being used to match donors and recipients.

Localized delivery of immunosuppressive regulatory T cells to peripheral nerve allografts promotes regeneration of branched segmental defects

Segmental injuries to peripheral nerves (PNs) too often result in lifelong disability or pain syndromes due to a lack of restorative treatment options. For injuries beyond a critical size, a bridging device must be inserted to direct regeneration. PN allografts from immunologically incompatible donors are highly effective bridging devices but are not a regular clinical option because of the expense and health risks of systemic immunosuppression (ISN). We have developed a method to deliver a single administration of ISN localized around a PN allograft that circumvents the risks of systemic ISN. Localized ISN was provided by regulatory T cells (Tregs), a potently immunosuppressive cell type, that was delivered around a PN allograft with a poly(ethylene glycol) norbornene (PEGNB) degradable hydrogel. Tregs are released from the hydrogel over 14 d, infiltrate the graft, suppress the host immune response and facilitate regeneration of the recipient rats equal to the autograft control. Furthermore, this method was effective in a segmental PN defect that included a branch point, for which there currently exist no treatment options. These results show that localized delivery of immunosuppressive cells for PN allografts is an effective new strategy for treating segmental PN defects that can also be used to regenerate complex nerve structures.