Redefining biomaterial biocompatibility: challenges for artificial intelligence and text mining

The surge in ‘Big data’ has significantly influenced biomaterials research and development, with vast data volumes emerging from clinical trials, scientific literature, electronic health records, and other sources. Biocompatibility is essential in developing safe medical devices and biomaterials to perform as intended without provoking adverse reactions. Therefore, establishing an artificial intelligence (AI)-driven biocompatibility definition has become decisive for automating data extraction and profiling safety effectiveness. This definition should both reflect the attributes related to biocompatibility and be compatible with computational data-mining methods. Here, we discuss the need for a comprehensive and contemporary definition of biocompatibility and the challenges in developing one. We also identify the key elements that comprise biocompatibility, and propose an integrated biocompatibility definition that enables data-mining approaches.Peer ReviewedPostprint (published version

The degradation of electrospun polydioxanone patches for rotator cuff repair

INTRODUCTION: Surgical repair of rotator cuff pathology has failure as high as 75% [1]. Biological factors such as stem cells and platelet rich plasma may improve the biological environment around the healing tendon [2]. We have investigated the use of a biocompatible and biodegradable electrospun polydioxanone (PDO) scaffold patch to restrain the spread of injected biological factors, and retain them in the desired locality. This study characterizes the degradation of PDO microfibrous patches in vitro. We have used imaging techniques, and high performance liquid chromatography to demonstrate the kinetics of PDO degradation as well as demonstrate the time scale of degradation in an in vitro representation of the physiological environment. METHODS: In-vitro weight loss: Electrospun polydioxanone patches were incubated in phosphate buffered solution (PBS) and weighed at intervals of 1 to 5 days over the course of 13 weeks. Weight loss of PDO samples was calculated as a percentage of the starting dry weight. Imaging: PDO samples were viewed in an Environmental Scanning Electron microscope (ESEM). Comparisons were made between fresh samples of PDO, and those degraded over a period of weeks in (PBS). The dimensions of the imaged fibres were measured and compared in order to characterize how they degraded. Fluorescent microscopy was used to image patches seeded with tendon-derived cells. These patches were incubated in PBS and imaged after 1, 2, and 4 weeks to demonstrate the adhesion of the cells to the electrospun fibres as the PDO degraded. High Performance Liquid Chromatography: HPLC was utilised to attempt to identify the final degradation product of polydioxanone, and to characterise the mechanisms by which it degrades. pH: PDO patches were incubated in PBS for a period of 8 weeks. At incremental time points, the pH of the solution was assessed. The Dynamic arm of the experiment involved replacing the PBS at each time point, in order to replicate the dynamic environment found in vivo. The Static arm maintained the same solution throughout the experiment. RESULTS AND DISCUSSION: The weight loss, pH, and imaging experiments provide evidence that PDO begins to significantly degrade at the 4 week time point. The ESEM images demonstrated the character of the PDO degradation, with degraded samples presenting short blocks of PDO in contrast to the long fibres of the fresh samples (Figure 3). It also provided evidence of the presence of live cells at the 4 week mark. The HPLC experiments also provided insight into the mechanisms of degradation and potential final degradation products. SIGNIFICANCE: The electrospun PDO structure maintains weight and pH well for 4 weeks which is the main window for physiological benefit from biological factors incorporated into the patch. Tenoblast cells maintain adhesion to the patch well, and the hypothesis formed from these results is that they will migrate onto the injury when exposed to physiological recruitment factors. REFERENCES: 1. Benson RT, McDonnell SM, Rees JL, Athanasou NA, Carr AJ. The morphological and immunocytochemical features of impingement syndrome and partial-thickness rotator-cuff tear in relation to outcome after subacromial decompression. The Journal of bone and joint surgery 2009 Jan;91(1):119-123. 2. de Mos M, van der Windt AE, Jahr H, van Schie HT, Weinans H, Verhaar JA, et al. Can platelet-rich plasma enhance tendon repair? A cell culture study. Am J Sports Med 2008 Jun;36(6):1171-1178.This thesis is not currently available in ORA

Time to kick-start text mining for biomaterials

The rapidly expanding biomaterials data are challenging to organize. Text mining systems are powerful tools that automatically extract and integrate information in large textual collections. As text mining leaps forward by leveraging deep-learning approaches, it is time to address the most pressing biomaterials information and data processing needs.Peer ReviewedPostprint (author's final draft

Spider and mulberry silkworm silks as compatible biomaterials

Silks are a diverse family of natural material with extraordinary mechanical properties such as high tensile strength and extensibility, as well as reported biological compatibility. In recent years, the reported exceptional nature of silk lead to increased interest in silk for biomedical applications. The aim of this review is to assess the potential and compatibility of silk fibres and silk-based materials for biomedical purposes. It will do so by reviewing silk properties, structure and formation, with special focus on spider and mulberry silkworm silk fibres, as well as the application of silk in the biomedical field. The review will begin by introducing the general characteristics of silk, and a consideration of properties of particular relevance to the use of silk in biomedical applications: degradation and tensile properties. Subsequently, the formation of silk in vitro will be outlined, as well as the current understanding of silk structure. A comparison of the structural differences between spider and silkworm silks will follow. Some of the different types of silk produced by orb weaving spiders, their main functuins and structural features will be described. This will be followed by an introduction to 'supercontraction', a phenomenon that has only been observed in spider silks, and is considered to be one of the major obstacles to the use of native spider silk for medical applications. Finally, there will be an account of previous biomedical applications of silk. It is the intention of this review to point out the wide range of excellent and valuable properties observed in different silk types, and to propose that silk's versatility is possibly its strongest advantage. However, in the context of biomedical research and development, there are still major limitations and difficulties with native silk fibres. It is suggested in this review that an artificially produced silk or silk-like material formed to possess specific desired properties will allow the overcoming of present limitations

Modulation of cell growth on exposure to silkworm and spider silk fibers

Recent years have seen an increased interest in the use of natural and modified silks for tissue engineering. Despite longstanding concerns regarding the biocompatibility of silk sutures, only a few studies have been carried out to investigate the biocompatibility of natural silk fibers. Here, we report an in vitro assessment of the effect of nonmodified, degummed silks on cells. We describe the effects of degummed silk fibers as well as extracted sericin on cell metabolism and proliferation. Endothelial cells directly exposed to native degummed Bombyx mori and Antheraea pernyi silks showed lower rates of proliferation and metabolism than nonexposed cells. A similar but milder effect was observed for cells in direct contact with Nephila edulis egg sack fibers. Sericin and silk-conditioned medium had no negative effect on cell proliferation except in medium supplemented with 5% bovine serum prior to conditioning with A. pernyi silk. The toxicity of A. pernyi was negligible after thorough enzymatic treatment of the fibers with typsin. It is, therefore, proposed that A. pernyi silk contain one or more cytotoxic components, which need to be removed prior to medical use

A quantitative label-free analysis of the extracellular proteome of human supraspinatus tendon reveals damage to the pericellular and elastic fibre niches in torn and aged tissue

<div><p>Tears of the human supraspinatus tendon are common and often cause painful and debilitating loss of function. Progressive failure of the tendon leading to structural abnormality and tearing is accompanied by numerous cellular and extra-cellular matrix (ECM) changes in the tendon tissue. This proteomics study aimed to compare torn and aged rotator cuff tissue to young and healthy tissue, and provide the first ECM inventory of human supraspinatus tendon generated using label-free quantitative LC-MS/MS. Employing two digestion protocols (trypsin and elastase), we analysed grain-sized tendon supraspinatus biopsies from older patients with torn tendons and from healthy, young controls. Our findings confirm measurable degradation of collagen fibrils and associated proteins in old and torn tendons, suggesting a significant loss of tissue organisation. A particularly marked reduction of cartilage oligomeric matrix protein (COMP) raises the possibility of using changes in levels of this glycoprotein as a marker of abnormal tissue, as previously suggested in horse models. Surprisingly, and despite using an elastase digestion for validation, elastin was not detected, suggesting that it is not highly abundant in human supraspinatus tendon as previously thought. Finally, we identified marked changes to the elastic fibre, fibrillin-rich niche and the pericellular matrix. Further investigation of these regions may yield other potential biomarkers and help to explain detrimental cellular processes associated with tendon ageing and tendinopathy.</p></div

Characterizing the macro and micro mechanical properties of scaffolds for rotator cuff repair

Background: Retearing after rotator cuff surgery is a major clinical problem. Numerous scaffolds are being used to try to reduce retear rates. However, few have demonstrated clinical efficacy. We hypothesize that this lack of efficacy is due to insufficient mechanical properties. Therefore, we compared the macro and nano/micro mechanical properties of 7 commercially available scaffolds to those of the human supraspinatus tendons, whose function they seek to restore. Methods: The clinically approved scaffolds tested were X-Repair, LARS ligament, Poly-Tape, BioFiber, GraftJacket, Permacol, and Conexa. Fresh frozen cadaveric human supraspinatus tendon samples were used. Macro mechanical properties were determined through tensile testing and rheometry. Scanning probe microscopy and scanning electron microscopy were performed to assess properties of materials at the nano/microscale (morphology, Young modulus, loss tangent). Results: None of the scaffolds tested adequately approximated both the macro and micro mechanical properties of human supraspinatus tendon. Macroscale mechanical properties were insufficient to restore load-bearing function. The best-performing scaffolds on the macroscale (X-Repair, LARS ligament) had poor nano/microscale properties. Scaffolds approximating tendon properties on the nano/microscale (BioFiber, biologic scaffolds) had poor macroscale properties. Conclusion: Existing scaffolds failed to adequately approximate the mechanical properties of human supraspinatus tendons. Combining the macroscopic mechanical properties of a synthetic scaffold with the micro mechanical properties of biologic scaffold could better achieve this goal. Future work should focus on advancing techniques to create new scaffolds with more desirable mechanical properties. This may help improve outcomes for rotator cuff surgery patients

The number of hits in each cellular compartment in samples digested by either trypsin (blue) or elastase (orange).

<p>Identified proteins (Progenesis, 2 or more peptides) were categorized using PANTHER classification system. Although tryspin digestion yielded more hits, there was a similar distribution of proteins in the compartments.</p

The relative abundance of collagens and their subunits in supraspinatus tendon from control and pathologic female and male donors.

<p>Dot plots show biological replicates, means and standard error of the mean. (A) COL1A1, (B) COL1A2, (C) COL3A1, (D), COL5A1, (E) COL5A2, (F) COL6A1, (G) COL6A2, (H) COL6A3 and (I) COL14A1. (J) Floating bars showing minimum and maximum relative abundance of the subunits of collagen I with a line at the mean and (K) the relative abundance of the subunits of collagen VI. (L) The ratio of collagen III to I, average of ratios in individual runs within each group (duplicates per sample, n = 18 per group). *P<0.05, **P<0.01 significantly different from control.</p

Previously published studies confirming the disruption of COL1, COL6, FBN1, COMP and LTBP2 in torn and/or aged tendons.

<p>Previously published studies confirming the disruption of COL1, COL6, FBN1, COMP and LTBP2 in torn and/or aged tendons.</p