Fluorescent Reporter Mice for Nerve Guidance Conduit Assessment: A High-Throughput in vivo Model.

OBJECTIVE: Use of cell culture and conventional in vivo mammalian models to assess nerve regeneration across guidance conduits is resource-intensive. Herein we describe a high-throughput platform utilizing transgenic mice for stain-free axon visualization paired with rapid cryosection techniques for low-cost screening of novel bioengineered nerve guidance conduit performance. METHODS: Interposition repair of sciatic nerve transection in mice expressing yellow fluorescent protein in peripheral neurons (Thy1.2 YFP-16) was performed with various bioengineered neural conduit compositions using a rapid sutureless entubulation technique under isoflurane anesthesia. Axonal ingrowth was assessed at 3 and 6 weeks using epifluorescent microscopy following cryosectioning. RESULTS: Mean procedure time (incision-to-closure) was less than 2½ minutes. Direct operational costs of a 3-week experiment was calculated at $21.47 per animal. Tissue processing steps were minimized to aldehyde fixation, cryoprotection and sectioning, and rapid fluorescent dye staining for conduit visualization. Fluorescent microscopy readily resolved robust axonal sprouting at 3 weeks, with clear elucidation of ingrowth-permissive, semipermissive, or restrictive nerve guidance conduit environments. CONCLUSION: A rapid and cost-efficient in vivo platform for screening of nerve guidance conduit performance has been described. LEVEL OF EVIDENCE: NA. Laryngoscope, E392-E392, 2018.

A cost-effective cell- and matrix-based minimally invasive single-stage chondroregenerative technique developed with validated vertical translation methodology.

Introduction The morbidity and significant health economic impact associated with the chondral lesion has led to a large number of strategies for therapeutic neochondrogenesis. The challenge has been to develop techniques that are cost effective single-stage procedures with minimal surgical trauma that have undergone rigorous preclinical scrutiny and robust reproducible assessment of effectiveness. A biological repair requires the generation of a cellular and matrix composite with appropriate signalling for chondrogenic differentiation. Methods and results A technique was developed that allowed chondrogenic primary (uncultured) cells from bone marrow aspirate concentrate, combined with a composite hydrophilic and fibrillar matrix to be applied arthroscopically to a site of a chondral lesion. The construct was tested in vitro and in animal experiments before clinical trials. Clinical trials involved 60 patients in a prospective study. Symptomatic International Cartilage Repair Society grade 3 and 4a lesions were mapped and treated. Pre- and postoperative clinical assessments showed statistically significant improved outcomes; Lysholm Knee Scoring Scale (mean 52.8 to > 76.4; P < 0.05) International Knee Documentation Committee (mean 39 to > 79 P < 0.05) and Knee injury and Osteoarthritis Outcome Score (64.5 to >89.2 P < 0.05). Postoperative magnetic resonance imaging was evaluated morphologically (magnetic resonance observation of cartilage repair tissue, average MOCART score 72) and qualitatively; the regenerate was comparable to native cartilage. Conclusions This technique is effective, affordable, requires no complex tools and delivers a single-stage treatment that is potentially accessible to any centre capable of performing arthroscopic surgery. Good clinical results were found to be sustained at five years of follow-up with a regenerate that appears hyaline like using multiple magnetic resonance measures.

Iliac crest autogenous bone graft versus alloplastic graft and guided bone regeneration in the reconstruction of atrophic maxillae: a 5-year retrospective study on cost-effectiveness and clinical outcome.

BACKGROUND: Reconstruction of the atrophic maxillae with autogenous bone graft and jawbone-anchored bridges is a well-proven technique. However, the morbidity associated with the concept should not be neglected. Furthermore, the costs for such treatment, including general anesthesia and hospital stay, are significant. Little data are found in the literature with regard to a cost-benefit approach to various treatment alternates. PURPOSE: The aim of this retrospective study was to compare from a health-economical and clinical perspective the reconstruction of the atrophic maxillae prior to oral implant treatment either with autogenous bone grafts harvested from the iliac crest or the use of demineralized freeze-dried bone (DFDB) in combination with a thermoplastic carrier (Regeneration Technologies Inc., Alachua, FL, USA) and guided bone regeneration (GBR). MATERIALS AND METHODS: A total of 26 patients (13 + 13) were selected and matched with regard to indication, sex, and age. The study was performed 5 years after the completion of the treatment. Implant survival, morbidity, and complications were analyzed. Furthermore, a detailed analysis of the total cost for the respective treatment modality was performed, including material, costs for staff, sick leave, etc. RESULTS: The study revealed no statistical difference with regard to implant survival for the respective groups. The average total cost, per patient, for the DFDB group was 22.5% of the total cost for a patient treated with autogenous bone grafting procedures. CONCLUSIONS: The study concluded that reconstruction of atrophic maxillae with a bone substitute material (DFDB) in combination with GBR can be performed with an equal treatment outcome and with less resources and a significant reduced cost in selected cases compared with autogenous bone grafts from the iliac crest.

Business models for biomaterials in regenerative medicine.

The emergence of new therapeutic methods and technologies, including those associated with regenerative medicine, has required new thinking about regulation, reimbursement and business models. Some of the issues that particularly relate to the materials used in these technologies are discussed in this article.