Poly-l-lactide-co-ε-caprolactone (PLCL) and poly-l-lactic acid (PLLA)/gelatin electrospun subacromial spacer improves extracellular matrix (ECM) deposition for the potential treatment of irreparable rotator cuff tears.

Biodegradable subacromial spacer implantation has become practicable for the treatment of irreparable rotator cuff tears (IRCT). However, the relative high degradation rate and inferior tissue regeneration properties of current subacromial spacer may lead to failure regards to long-term survival. It is reported that satisfactory clinical results lie in the surrounding extracellular matrix (ECM) deposition after implantation. This study aims to develop a biological subacromial spacer that would enhance tissue regeneration properties and results in better ECM deposition. Physicochemical properties were characterized on both poly-l-lactide-co-ε-caprolactone (PLCL) dip-coating spacer (monolayer spacer, MS) and PLCL dip-coating + Poly-l-Lactic Acid (PLLA)/Gelatin electrospun spacer (Bilayer Spacer, BS). Cytocompatibility, angiogenesis, and collagen inducibility were evaluated with tendon fibroblasts and endothelial cells. Ultrasonography and histomorphology were used to analyze biodegradability and surrounding ECM deposition after the implantation in vivo. BS was successfully fabricated with the dip-coating and electrospinning technique, based on the human humeral head data. In vitro studies demonstrated that BS showed a greater cytocompatibility, and increased secretion of ECM proteins comparing to MS. In vivo studies indicated that BS promoted ECM deposition and angiogenesis in the surrounding tissue. Our research highlights that BS exhibits better ECM deposition and reveals a potential candidate for the treatment of IRCT in future.

Clinical application of polylactic acid/gelatin nanofibre membrane in hard-to-heal lower extremity venous ulcers.

OBJECTIVE: To evaluate the safety and effectiveness of polylactic acid/gelatin nanofibre membranes (PGNMs) in treating hard-to-heal lower extremity venous ulcer wounds. METHOD: In this prospective study, patients with venous leg ulcers (VLUs) were treated with PGNMs or standard of care. Wounds were assessed once a week until the wound was fully healed. RESULTS: The treatment group was comprised of 10 patients with VLUs, aged between 47-64 years, with an average age of 56.58±6.19 years. The wounds were located in the lower leg and/or ankle. Average wound area was 8.91±13.57cm2 (range: 1.5-52.5cm2). Average wound healing time was 18.75±16.36 days. Of the patients, nine (90%) rated their pain as lighter when removing the dressing, with an average pain value of 2.0±1.0 points. There was less secondary trauma to the wound surface, and less bleeding. At six months after the wound healing, the scar evaluation (using the Vancouver Scar Scale) result was 3.75±1.96 points. CONCLUSION: In this study, the PGNMs were safe and effective in treating hard-to-heal lower extremity VLUs.

Anterior substitutional urethroplasty using a biomimetic poly-l-lactide nanofiber membrane: Preclinical and clinical outcomes.

The aim of this study is to investigate the feasibility and efficacy of a novel biomimetic poly-l-lactide (PLLA) nanofiber membrane in repairing anterior urethral strictures from both preclinic and clinic. Biomimetic PLLA membrane was fabricated layer by layer according to the structure of human extracellular matrix. Microstructure, tensile strength, and suture retention strength were fully assessed. Before the clinical application, the safety and toxicology test of the biomimetic PLLA membrane was performed in vitro and in experimental animals. The patients underwent urethroplasty used dorsal onlay or lateral onlay technique. Then, they were followed up for 1 month, 3 months, 6 months, and then annually after the surgery. The mechanical experiments showed well property for application. Biomimetic PLLA membrane was safe according to the in vitro and animal studies. Then, a total of 25 patients (mean age 48.96 years) were included in the study from September 2016 to December 2018. After a mean follow-up of 33.56 months, 20 patients successfully treated with biomimetic PLLA membrane. Five patients (2 bulbar and 3 penile) suffered postoperational urethral stricture recurrence. None of infection or urinary fistula or any other adverse events related to the use of biomimetic PLLA membrane were observed during the follow-up period for all patients. The preliminary result confirmed the feasibility and efficacy of the biomimetic PLLA membrane as a novel material for anterior urethral repair. The long-term effects with more patients should be investigated in further studies.

Instant in-situ Tissue Repair by Biodegradable PLA/Gelatin Nanofibrous Membrane Using a 3D Printed Handheld Electrospinning Device.

Background: This study aims to design a 3D printed handheld electrospinning device and evaluate its effect on the rapid repair of mouse skin wounds. Methods: The device was developed by Solidworks and printed by Object 350 photosensitive resin printer. The polylactic acid (PLA)/gelatin blend was used as the raw material to fabricate in-situ degradable nanofiber scaffolds. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and water vapor permeability test were used to evaluate the material properties of the scaffolds; cytotoxicity test was performed to evaluate material/residual solvent toxicity, and in situ tissue repair experiments in Balb/c mouse were performed. Results: The 3D printed handheld electrospinning device successfully fabricates PLA/gelatin nanofibrous membrane with uniformly layered nanofibers and good biocompatibility. Animal experiments showed that the mice in the experimental group had complete skin repair. Conclusions: The 3D printed handheld device can achieve in situ repair of full-thickness defects in mouse skin.

Role and mechanisms of a three-dimensional bioprinted microtissue model in promoting proliferation and invasion of growth-hormone-secreting pituitary adenoma cells.

Growth-hormone-secreting pituitary adenoma (GHSPA) is a benign tumour with a high incidence and large economic burden, which greatly affects quality of life. The aetiological factors are yet to be clarified for GHSPA. Conventional two-dimensional (2D) monolayer culture of tumour cells cannot ideally reflect the growth status of tumours in the physiological environment, and insufficiencies of in vitro models have severely restricted the progress of cancer research. Three-dimensional (3D) bioprinting technology is being increasingly used in various fields of biology and medicine, which allows recapitulation of the in vivo growth environment of tumour cells. In this study, a GHSPA microtissue model was established using 3D bioprinting. Tumour cells in the 3D environment exhibited more active cell cycle progression, secretion, proliferation, invasion, and tumourigenesis compared with those in the 2D environment. Furthermore, the molecular mechanisms of the 3D-printed microtissue model were explored. We demonstrated that the 3D-printed microtissue provides an excellent in vitro model at the tissue level for oncological research and may facilitate in-depth studies on the aetiology, treatment, drug resistance, and long-term prognosis of GHSPA .

Clinical application of a 3D-printed scaffold in chronic wound treatment: a case series.

OBJECTIVE: This case series evaluates the safety and effectiveness of 3D-printed scaffold in chronic wounds. The scaffold is a composite of natural and synthetic materials, and can be prepared in the form of powder or membrane. METHOD: We recruited patients with pressure ulcera (PU) and/or a diabetic foot ulcers (DFU). We used two methods: 3D-printed scaffolds alone, or 3D-printing powder mixed with platelet-rich fibrinogen (PRF). Clinicians and patients were asked to rate the scaffold's ease of application and comfort during use. RESULTS: A total of five patients were recruited; four with a PU and one with a DFU. For the patient treated with the 3D-printed scaffold membrane (n=1), their PU healed in 28 days, and for patients treated with the 3D-printed scaffold powder (n=2), their PUs healed in 54 days. For the patients treated with the 3D-printing powder mixed with PRF (n=2), the patient with a PU healed in 11 days, and the patient with the DFU healed in 14 days. All clinicians rated the 3D-printed scaffold as 'easy' or 'very easy' to use, and patients rated their comfort during wear and at dressing change as 'good' or 'very good'. CONCLUSION: This study demonstrated that 3D-printed scaffold was convenient to use, have the potential to improve wound healing rates, and provided a safe and effective way for treating chronic wounds.

A novel biomimetic composite substitute of PLLA/gelatin nanofiber membrane for dura repairing.

OBJECTIVE: Biomimetic design will significantly improve growth and regeneration of dural cells and tissue for better repairing effects and fewer complications in repairing the native dura. This study designed a novel composite, biomimetic substitute based on the characteristics of native dura extracellular matrix. METHODS AND RESULTS: This substitute is expected to rapidly induce cell adhesion, migration, and fast regeneration of neotissue. The material characteristics (contact angle, surface charge, and zeta potential were evaluated), in vitro biological characteristics (cell stretch, connections between cells, cell proliferation) and in vivo tissue regeneration capability of this substitute were evaluated, compared to those of collagen dura substitute, the mostly used dura substitute. The results showed that the surface properties of this composite substitute were more biomimetic to native extracellular matrix than collagen substitute did, together with better cytocompatibility, tissue ingrowth, and neoangiogenesis. This composite substitute further demonstrated in clinical case study its ideal repair effect with no CSF leakage or other adverse reactions. CONCLUSION: In conclusion, the new biomimetic composite substitute provides alternative substitute for dura repairing.

Evaluation of efficacy and biocompatibility of a new absorbable synthetic substitute as a dural onlay graft in a large animal model.

BACKGROUND: Numerous dura substitutes are commercially available, but no absorbable synthetic dura repair product has been used for both onlay and suture applications. OBJECTIVE: The safety and effectiveness of a new absorbable synthetic substitute composed of Poly-L-lactide microfibers as onlay dural graft were evaluated. METHODS: Physical properties and performance of the microfibrous synthetic dural substitute implanted as an onlay or suturable grafts were compared with these commercial products, including CODMAN ETHISORB™ Dura Patch and DuraGen™ Dural Graft Matrix, in a canine duraplasty model. The cerebrospinal fluid (CSF) leakage, macroscopic and microscopic observation at 30 and 90 days after implantation were investigated. RESULTS: The absorbable synthetic dural substitute exhibited good wettability and conformability. When implanted as an onlay graft, it can prevent CSF leakage and integrate with the surrounding tissue to repair dural defects, indicating its good efficacy and biocompatibility as an onlay graft. CONCLUSION: Based on the excellent physical properties and performances mentioned above, the new absorbable synthetic substitute can be applied as a dural graft for both onlay and suturable applications.

A New Absorbable Synthetic Substitute With Biomimetic Design for Dural Tissue Repair.

Dural repair products are evolving from animal tissue-derived materials to synthetic materials as well as from inert to absorbable features; most of them lack functional and structural characteristics compared with the natural dura mater. In the present study, we evaluated the properties and tissue repair performance of a new dural repair product with biomimetic design. The biomimetic patch exhibits unique three-dimensional nonwoven microfiber structure with good mechanical strength and biocompatibility. The animal study showed that the biomimetic patch and commercially synthetic material group presented new subdural regeneration at 90 days, with low level inflammatory response and minimal to no adhesion formation detected at each stage. In the biological material group, no new subdural regeneration was observed and severe adhesion between the implant and the cortex occurred at each stage. In clinical case study, there was no cerebrospinal fluid leakage, and all the postoperation observations were normal. The biomimetic structure and proper rate of degradation of the new absorbable dura substitute can guide the meaningful reconstruction of the dura mater, which may provide a novel approach for dural defect repair.