Plate-on-plate technique for treating peri-implant fractures of distal femoral locking plate: a retrospective study of 11 patients.

INTRODUCTION: In this study, we aimed to ascertain the feasibility and reliability of the plate-on-plate technique for peri-implant fractures of the distal femoral locking plate when the distal femoral fracture is still unhealed. MATERIALS AND METHODS: From January 2007 to December 2016, we enrolled 11 patients who received treatment at our institution. All patients underwent at least 1 year of follow-up. Their medical records, imaging studies, visual analogue scores, walking ability, complications, and functional outcomes at 1 year postoperative based on the Short Form (36) Health Survey (SF-36) scores were retrospectively evaluated. RESULTS: The average follow-up duration was 20.5 (range 15-30) months. All fractures united with satisfactory alignment, and the average time for union was 27.5 (range 16-40) weeks. The average SF-36 scores at 1 year postoperative was 79.2 (range 72-90). Regarding ambulatory status, all patients could perform unrestricted outdoor ambulation. CONCLUSION: In our case series, the plate-on-plate technique achieved a good bone union rate and functional outcomes with low complication rates and thus may be a good alternative for managing this difficult type of fracture.

An Acellular, Self-Healed Trilayer Cryogel for Osteochondral Regeneration in Rabbits.

Osteochondral regeneration remains formidable challenges despite significant advances in microsurgery. Herein, an acellular trilayer cryogel (TC) with injectability, tunable pore sizes (80-200 µm), and appropriate compressive modulus (10.8 kPa) is manufactured from self-healable hydrogel under different gelling times through Schiff reaction between chitosan and difunctionalized polyurethane (DFPU). Bioactive molecules (Y27632 and dexamethasone) are respectively loaded in the top and bottom layers to form the Y27632/dexamethasone-loaded trilayer cryogel (Y/DEX-TC). Mesenchymal stem cells (MSCs) seeded in Y/DEX-TC proliferated ≈350% in vitro and underwent chondrogenesis or osteogenesis in response to the respective release of Y or DEX in 14 days. Acupuncture is administered to animals in an attempt to modulate the innate regulatory system and mobilize endogenous MSCs for osteochondral defect regeneration. In vivo rabbit experiments using Y/DEX-TC combined with acupuncture successfully regulate SDF-1 and TGF-ß1 levels, which possibly cause MSC migration toward Y/DEX-TC. The synergistic effect of cryogel and acupuncture on immunomodulation is verified with a ≈7.3-fold enhancement of the M2-/M1-macrophage population ratio by treatment of Y/DEX-TC combining acupuncture, significantly greater than ≈1.5-fold increase by acupuncture or ≈2.2-fold increase by Y/DEX-TC alone. This novel strategy using acellular drug-loaded cryogel and accessible acupuncture shows promise in treating osteochondral defects of joint damage.

Cryogel/hydrogel biomaterials and acupuncture combined to promote diabetic skin wound healing through immunomodulation.

Unhealed chronic wounds often deteriorate into multiple infection with several kinds of bacteria and excessive proteolytic wound exudate and remains one of the common healthcare issues. Here, the functional and antimicrobial hydrogel and cryogel biomaterials were prepared from glycol chitosan and a novel biodegradable Schiff base crosslinker difunctional polyurethane (DF-PU). The cryogel exhibited ~2730 ± 400% of water absorption with abundant macropores and 86.5 ± 1.6% of porosity formed by ice crystal as well as ~240% cell proliferation effect; while the hydrogel demonstrated considerable antimicrobial activity and biodegradability. As an optimized procedure to treat the diabetic skin wound in a rat model, the combined application of adipose stem cell-seeded cryogel/hydrogel biomaterials on the wound and acupuncture surrounding the wound may attain 90.34 ± 2.3% of wound closure and secure the formation of granulation tissue with sufficient microvessels and complete re-epithelialization in 8 days. The average increases in the superficial temperature of wounded animals after acupuncture were about 1-2 °C. Through the activation of C3a and C5a, the increased secretion of cytokines SDF-1 and TGFß-1, as well as the down-regulation of proinflammatory cytokines TNF-α and IL-1ß, the combined treatment of stem cell-seeded cryogel/hydrogel biomaterials and acupuncture on wounds produced synergistic immunomodulatory effects. The strategy using the combined treatment of biomaterials, stem cells, and acupuncture reveals a perspective new approach to accelerate the tissue regeneration.

Ipsilateral vascularised fibula with external locking plate for treatment of massive tibial bone defects.

INTRODUCTION: Management of massive tibial bone defects remains challenging for orthopaedic doctors. This study aimed to ascertain the viability and reliability of utilising an ipsilateral vascularised fibula with an external locking plate for the difficult situation. MATERIALS AND METHODS: Between January 2012 and December 2017, eight patients (7 men) with a mean age of 32.3 (19-54) years who presented with massive tibial bone defects were treated using the described technique. The mean length of the bone defect was 12.4 (8-20) cm. The patients were assessed for clinical and radiographic results, hypertrophy of the fibular graft with DeBoer and Wood's method, and SF-36 functional score. RESULTS: The mean follow-up period was 40.3 (26-60) months. The average time for union was 5.6 (3-8) months. At the final follow-up, all patients had fully united grafts and walked without restriction. The mean graft hypertrophy index was 98.2 %. The SF-36 score was > 75 % in five patients, and 50-75 % in three. Three patients had a leg length discrepancy of > 1.5 cm. Two patients with equinus foot were treated using tibiotalocalcaneal fusion. Three patients had pin-tract infections. Four screws were broken in two cases. CONCLUSION: Ipsilateral vascularised fibular transfer combined with an external locking plate as a definitive external fixator provides a simple and comfortable treatment, and appropriate mechanical loading and vascularisation of the graft site to achieve hypertrophy of the fibular graft. Hence, our technique can serve as a valuable alternative for the treatment of massive tibial bone defects.

Inhibiting two cellular mutant epidermal growth factor receptor tyrosine kinases by addressing computationally assessed crystal ligand pockets.

Aim: Blocking receptor tyrosine kinases is a useful strategy for inhibiting the overexpression of EGFR. However, the quality of crystal pocket is an essential issue for virtually identifying new leads for surviving resistance cancer cells. Results: With the examinating crystal pocket quality by the self-docking root-mean-square deviation (RMSD) calculation, we used the two best kinase pockets of mutant EGFR kinases, T790M/L858R and G719S, for virtual screening. After sorting all the docking poses of the 57,177 library compounds by consensus scores, three evidently blocked cellular EGFR phosphorylation in the H1975 and SW48 cell lines. Conclusion: The computationally assessed qualities of crystal pockets of crystal EGFR kinases can help identify new cellular active and target-specific ligands rapidly and at low cost.

Transcription-independent and -dependent p53-mediated apoptosis in response to genotoxic and non-genotoxic stress.

We previously reported that p53-mediated apoptosis is determined by severity of DNA damage, not by the level of p53, in doxorubicin-treated prostate cancer cells. In addition to doxorubicin, our results here indicated that camptothecin and bortezomib, which are a topoisomerase 1 poison and a 26 S proteasome inhibitor, respectively, could also induce apoptosis in a p53-dependent manner in prostate cancer. Then, we examined whether p53-mediated apoptosis induced by genotoxic and non-genotoxic stress occur in the same or a different way. By using dominant negative p53 to compete with wild-type p53 in transcription activity, we demonstrated that p53-mediated apoptosis in response to doxorubicin- or camptothecin-induced genotoxic stress is transcription-independent. In contrast, p53-mediated apoptosis from bortezomib-induced stress is transcription-dependent. Interestingly, we also found that doxorubicin-induced p21 expression is activated by p53 in transcription-dependent manner, while camptothecin-induced p21 expression is p53-independent. We then investigated the p53 ratio of nucleus to cytosol corresponding to low and high dose doxorubicin, camptothecin, or bortezomib treatment. The results suggested that p53 translocation from cytoplasm to nucleus actively drives cells toward apoptosis in either transcription-dependent or -independent manner for responding to non-genotoxic or genotoxic stress, respectively.