3D Niche-Inspired Scaffolds as a Stem Cell Delivery System for the Regeneration of the Osteochondral Interface.

The regeneration of the osteochondral unit represents a challenge due to the distinct cartilage and bone phases. Current strategies focus on the development of multiphasic scaffolds that recapitulate features of this complex unit and promote the differentiation of implanted bone-marrow derived stem cells (BMSCs). In doing so, challenges remain from the loss of stemness during in vitro expansion of the cells and the low control over stem cell activity at the interface with scaffolds in vitro and in vivo. Here, this work scaffolds inspired by the bone marrow niche that can recapitulate the natural healing process after injury. The construct comprises an internal depot of quiescent BMSCs, mimicking the bone marrow cavity, and an electrospun (ESP) capsule that "activates" the cells to migrate into an outer "differentiation-inducing" 3D printed unit functionalized with TGF-ß and BMP-2 peptides. In vitro, niche-inspired scaffolds retained a depot of nonproliferative cells capable of migrating and proliferating through the ESP capsule. Invasion of the 3D printed cavity results in location-specific cell differentiation, mineralization, secretion of alkaline phosphatase (ALP) and glycosaminoglycans (GAGs), and genetic upregulation of collagen II and collagen I. In vivo, niche-inspired scaffolds are biocompatible, promoted tissue formation in rat subcutaneous models, and regeneration of the osteochondral unit in rabbit models.

Topology optimization of a mandibular reconstruction plate and biomechanical validation.

OBJECTIVES: Reconstruction plates, used to bridge segmental defects of the mandible after tumor resection or traumatic bone tissue loss, are subjected to repeated stresses of mastication. High stress concentrations in these plates can result in hardware failure. Topology optimization (TO) could reduce the peak stress by computing the most optimal material distribution in a patient-specific implant (PSI) used for mandibular reconstruction. The objective of this study was biomechanical validation of a TO-PSI. METHODS: A computer-aided design (CAD) model with a segmental defect was created based on the geometry of a polyurethane mandible model. A standard-PSI was designed to bridge the defect. A TO-PSI was then designed with a maximum stress equal to the ultimate tensile stress of Ti6Al4V (930 MPa) during a loading condition of 378 N. Finite element analysis (FEA) was used to analyze stresses in both PSI designs during loading. The standard-PSI and TO-PSI designs were produced in triplicate by selective laser melting of Ti6Al4V, fixated to polyurethane mandible models with segmental defects identical to the CAD model, and subsequently subjected to continuous compression with a speed of 1 mm/min on a universal testing machine, while recording the load. Peak loads before failure in the TO-PSI group within a 30% range of the predicted peak load (378 N) were considered a successful biomechanical validation. RESULTS: Fracture of the TO-PSI occurred at a median peak load of 334 N (range 304-336 N). These values are within the 30% range of the predicted peak load. Fracture of the mandible model in the standard-PSI group occurred at a median peak load of 1100 N (range 1010-1460 N). Failure locations during biomechanical testing of TO-PSI and standard-PSI samples corresponded to regions in the FEA where stresses exceeded the ultimate tensile strength of titanium and polyurethane, respectively. CONCLUSION: This study demonstrates a successful preliminary biomechanical validation of TO in the design process for mandibular reconstruction plates. Further work is needed to refine the finite element model, which is necessary to ultimately design TO-PSIs for clinical use.

Computer-Aided-Design/Computer-Aided-Manufacturing Titanium Cranioplasty in a Child: Critical Appraisal.

Large skull bone defects of the cranial vault can result from various reasons. Reconstruction of these defects is performed for protective and aesthetic reasons but is also required for adequate intracranial homeostasis. Computer-aided-design/computer-aided-manufacturing (CAD/CAM) patient-specific skull implants have become the most valuable alternative to the traditional methods of reconstruction and a growing number of publications is dealing with this topic in adults. Literature related to the application of these implants in pediatric cranioplasty is, however, still scarce.The authors present a case of a 9-year-old boy, where cranioplasty using a CAD/CAM additive manufactured titanium implant led to improvement of symptoms attributed to cerebrospinal fluid circulation problems and intracranial homeostasis disbalance. The authors further reflect on what the role of cranioplasty should be in the therapeutic treatment plan.

Cranioplasty with patient-specific implants in repeatedly reconstructed cases.

OBJECTIVE: Cranioplasty is indicated to restore form and function of bone defects of the neurocranium. Autografts are the gold standard, alloplastic materials are used when autologous bone is unavailable or unsuitable, and increasing evidence supports the use of patient-specific implants (PSIs) for reconstruction. We reviewed our own patient data to assess pre- and intraoperative aspects, complications and costs in patients that were treated with PSIs from titanium or polyetheretherketone (PEEK) for skull bone reconstruction. METHODS: We retrospectively evaluated all patients receiving a PSI as at least a secondary reconstruction between 2004 and 2016 at Maastricht University Medical Center. These cases were analyzed for demographics, perioperative surgical and medical aspects, as well as costs. RESULTS: In total 30 patients received PSIs, of which 20 were included in this study. Duration of PSI placement was not statistically different between group I, where previously placed reconstruction material was still in situ, and group II, where no remaining previously placed reconstruction material was present (group I: 104 ± 27 mins, group II: 86 ± 36 mins; p = 0.27). Postoperatively, 2 patients experienced complications (10%). Costs of obtaining the PSIs were not significantly different between group I and group II (group I: mean EUR 7536 ± 2759, group II: mean EUR 8351 ± 2087, p = 0.51). CONCLUSION: Treatment of skull bone defects in repeated reconstruction requires an optimal preoperative planning and intraoperative procedure. In this retrospective study comparing repeatedly reconstructed cases with and without remaining previously placed reconstruction material present at the surgical site, we could not find significant differences in the duration of the surgical procedure nor costs of obtaining the PSIs. The protocol followed at MUMC for preoperative planning, manufacturing, and surgery, represents the current state-of-the-art treatment.

The therapeutic effect of patient-specific implants in cranioplasty.

OBJECTIVE: Patient specific implants have been used for the reconstruction of large skull bone defects. Several therapeutic effects have been suggested in current literature but were never objectified. The aim of the current study was to evaluate the change in quality of life, pain, aesthetics, and the surgical and medical outcomes after reconstruction of large skull bone defects with titanium or polyetheretherketone (PEEK) implants. METHODS: We retrospectively evaluated 29 consecutive patients receiving a patient specific skull implant between November 2004 and December 2015. Twenty-one patients received PEEK implants and eight received titanium implants. Data was acquired regarding quality of life, aesthetics, pain, demographics and complications. Quality of life was measured using the Glasgow Benefit Inventory (GBI). Additional questions were asked concerning pain, satisfaction and aesthetics. RESULTS: The mean total GBI-score was +26.1 (95%CI 16.8-35.4, p < 0.001). Headache complaints or pain in the operation site improved in 75.0% and 77.8% of these patients, respectively. In 8.0% an increase was seen with regard to both variables. CONCLUSION: Reconstruction of skull bone defects with PEEK and titanium patient specific implants gave a statistically significant improvement in quality of life. Furthermore, it decreased pain and headaches and gave aesthetically good results.

Interval cranioplasty with patient-specific implants and autogenous bone grafts--success and cost analysis.

UNLABELLED: Different options exist for the reconstruction of craniectomy defects following interval cranioplasty. The standard procedure is still based on the re-implantation of autogenous bone specimen which can be stored in the abdominal wall or be cryopreserved. Alternatively patient-specific implants (PSIs) can be used. We conducted a retrospective study based on 50 consecutive patients with skull bone defects of 100 cm(2) or more being operated on by the same team of surgeons. Thirty-three patients agreed to take part in the study. Seventeen patients who underwent reconstruction with PSIs (titanium and polyether ether ketone, PEEK) (follow-up, 43 months [range, 3-93]) were compared with 16 control subjects who had autogenous bone grafts re-implanted (follow-up, 32 months [range, 5-92]). Criteria analyzed were the success and complication rates, operation time, duration of hospitalization and the treatment costs. Complication rate and the rate of reoperation were significantly lower, and the hospital stay was shorter in the PSI group. The treatment costs for reconstruction with autogenous bone were considerably lower than skull bone reconstruction based on PSIs (average costs: 10849.91 €/patient versus 15532.08 €/patient with PSI). Due to biological reasons some of the autogenous bone implants fail due to infection and resorption and the patients have to undergo another operation with implantation of a PSI in a secondary attempt. For those patients the highest overall treatment costs must be calculated (average costs: 26086.06 €/patient with secondary stage PSI versus 15532.08 €/patient with primary stage PSI). CONCLUSION: High success rates and reliability of PSIs may change the treatment strategy in patients undergoing interval cranioplasty.

A treatment algorithm for patients with large skull bone defects and first results.

Large skull bone defects resulting from craniotomies due to cerebral insults, trauma or tumours create functional and aesthetic disturbances to the patient. The reconstruction of large osseous defects is still challenging. A treatment algorithm is presented based on the close interaction of radiologists, computer engineers and cranio-maxillofacial surgeons. From 2004 until today twelve consecutive patients have been operated on successfully according to this treatment plan. Titanium and polyetheretherketone (PEEK) were used to manufacture the implants. The treatment algorithm is proved to be reliable. No corrections had to be performed either to the skull bone or to the implant. Short operations and hospitalization periods are essential prerequisites for treatment success and justify the high expenses.