Personalized Offloading Treatments for Healing Plantar Diabetic Foot Ulcers

Abstract

Background:

Non-removable knee-high devices are the gold-standard offloading treatments to heal plantar diabetic foot ulcers (DFUs). These devices are underused in practice for a variety of reasons. Recommending these devices for all patients, regardless of their circumstances and preferences influencing their ability to tolerate the devices, does not seem a fruitful approach.

Purpose:

The aim of this article is to explore the potential implications of a more personalized approach to offloading DFUs and suggest avenues for future research and development.

Methods:

Non-removable knee-high devices effectively heal plantar DFUs by reducing plantar pressure and shear at the DFU, reducing weight-bearing activity and enforcing high adherence. We propose that future offloading devices should be developed that aim to optimize these mechanisms according to each individual’s needs. We suggest three different approaches may be developed to achieve such personalized offloading treatment. First, we suggest modular devices, where different mechanical features (rocker-bottom sole, knee-high cast walls/struts, etc.) can be added or removed from the device to accommodate different patients’ needs and the evolving needs of the patient throughout the treatment period. Second, advanced manufacturing techniques and novel materials could be used to personalize the design of their devices, thereby improving common hindrances to their use, such as devices being heavy, bulky, and hot. Third, sensors could be used to provide real-time feedback to patients and clinicians on plantar pressures, shear, weight-bearing activity, and adherence.

Conclusions:

By the use of these approaches, we could provide patients with personalized devices to optimize plantar tissue stress, thereby improving clinical outcomes.

Introduction

Diabetic foot ulcers (DFUs) are a common and devastating long-term consequence of diabetes, resulting in significant suffering, disability, and health care costs.^1,2 For individuals with DFUs located on the plantar surface of the foot, offloading is arguably the most important intervention proven to heal ulcers faster.^3,4 International ³ and national^5-7 evidence-based guidelines strongly recommend non-removable knee-high offloading devices as the first choice treatment to offload and heal neuropathic plantar DFUs. Yet, despite being the gold-standard offloading treatments to heal plantar DFUs, these devices remain considerably underused in clinical practice.^4,8-12

Non-removable knee-high devices (NRKHDs) include total contact casts (TCCs) and non-removable knee-high walkers. A TCC is a custom-made, non-removable cast that maintains total contact with the entire plantar surface and lower leg. ³ A non-removable knee-high walker is a prefabricated walker rendered non-removable to the patient by wrapping it with plaster of Paris, cohesive bandage, or by securing it to the leg with a plastic lace.^3,13,14 Challenges associated with TCCs, such as time and clinical expertise needed to apply the cast, ¹² have been addressed with the more recent adoption of the non-removable knee-high walker. Despite these efforts, considerable barriers to more frequent use remain. These include patients rejecting devices due to potential interference with gait, balance, and daily activities, such as working, driving, and sleeping.^11,12 In a US survey, 55% of clinicians reported these patient-tolerance factors affected TCC uptake, ¹² and Australian clinical surveys reported the potential restriction of daily activities to be one of the most common considerations when selecting offloading devices. ¹¹ Thus, recommending these offloading treatments for every patient, without considering their circumstances and preferences influencing their ability to tolerate the devices, is an ineffective approach. A more flexible and personalized approach to offloading treatment is desirable if we are to increase the overall use and efficacy of offloading treatments and in turn heal more DFUs.

Personalized medicine is defined as

a medical model using characterization of individuals’ phenotypes and genotypes . . . for tailoring the right therapeutic strategy for the right person at the right time, and/or to determine the predisposition to disease and/or to deliver timely and targeted prevention. ¹⁵

However, to our knowledge, personalized medicine has so far received limited attention in research to prevent diabetic foot disease ¹⁶ and no research to treat diabetic foot disease. This article aims to explore the potential of a more personalized approach to offloading DFUs and suggests avenues for future research and development. We start with an analysis of the mechanisms of current gold-standard offloading devices to investigate how the effective mechanisms of these devices might be integrated into future devices to meet individual patients’ needs.

Ulcer-Healing Mechanisms of NRKHDs

The NRKHDs more effectively heal plantar DFUs, than all other existing offloading treatments, because of its ability to reduce plantar tissue stress, that is, “the accumulation of all mechanical stresses on an area of plantar foot tissue from all weight-bearing activity over time.” ¹⁷ Plantar tissue stress is a concept that integrates mechanical factors of relevance to the diabetic foot (plantar pressure [PP], shear stress, weight-bearing activity, and adherence to wearing the offloading intervention) into one overarching measure, and thus is a useful concept when analyzing ulcer-healing mechanisms of offloading devices. ¹⁷ The NRKHD reduces plantar tissue stress by (1) reducing PP and shear stress at the DFU, (2) reducing weight-bearing activity (by being difficult to walk with the device), and (3) enforcing adherence to using the device (by being non-removable to the patient). ¹⁸ We review the influence that each of these factors has on effective DFU healing below.

Reduction of PP and Shear Stress at the DFU

The greater the mechanical load (PP and shear stress) on a DFU, the longer it will stay in a chronic inflammatory and unhealed state ¹⁹ ; therefore, reducing these loads is a crucial part of the treatment. ³ Theoretically, this is achieved by redirecting load away from the affected area of the foot and/or shifting the reliance on mobility toward the contralateral limb. Previous reviews in the area have found that NRKHDs reduce more PP than other offloading treatments by incorporating more key mechanical features, such as customized insoles/foot-device interfaces, rocker-bottom soles, controlled ankle motion, and higher cast walls/struts preferably extending up to the knee. ²⁰ These features typically also reduce foot and ankle joint movements^21-23 and subsequent horizontal shear forces by using the contact surfaces as load-bearing surfaces. ²⁴ In addition, restricted ankle movement will necessitate strategies of reducing mobility and/or increasing requirements on the contralateral limb. Both strategies shift reliance away from the affected plantar location.

However, the need to reduce PP is not equivalent for all patients as the magnitude of PP varies depending on variations in an individual’s body weight, foot deformities, gait style, walking speed, and so on.^25,26 Although knee-high devices reduce PP more effectively than other treatments, prescribing them to all patients may result in a much greater reduction of PP than necessary for some patients, plus, at the same time, some of the important mechanical features (eg, rocker sole and immobilized ankle joint) may also adversely exacerbate gait and balance difficulties,^27,28 resulting in low acceptance of the treatment, low adherence to wearing the device, and potentially higher risk of adverse events such as falls. Hence, a more personalized approach to PP reduction is needed.

Reduction of Weight-Bearing Activity

Patients with plantar DFUs are typically advised to reduce weight-bearing activity, regardless of the offloading treatment they are prescribed or use.^29,30 In addition, weight-bearing activity has been found to reduce further when prescribing a device that is difficult to walk with, such as a knee-high device, the so-called “ball and chain effect.” ³¹ The rationale for reducing weight-bearing activity in offloading devices is that while devices typically reduce PP, they do not completely eliminate these PP. ³² Hence, any weight-bearing activity even at low PP still has potential to add stress to the ulcer site and prolong healing. A recent review ³³ found only six studies (in nine publications)^34-42 that have partially explored the effect of weight-bearing activity in offloading devices on ulcer-healing outcomes. One study^38,39 found that more daily steps were associated with slower ulcer healing; three studies^35,36,40,41 found no significant association (although two studies may have been underpowered); and in two studies,^34,37 the association was unclear. Thus, there may be a positive effect on ulcer healing by using devices that make gait and in turn weight-bearing activity more difficult, although the evidence for this conclusion is weak. However, the potential negative relationship between daily activity and healing may not be linear with one study finding that less than 3000 daily steps did not impair healing,^38,39 which is more than many DFU patients walk. ⁴³ Devices that are difficult to walk with likely reduces activity most in people who already are sedentary due to gait and balance issues, and have less effect on patients who are more healthy and active. Furthermore, weight-bearing activity is typically recommended for cardiovascular health and reducing such activity in people with DFU who typically have significant cardiovascular comorbidities ⁴⁴ is unlikely to improve their health. Thus, reducing weight-bearing activity in offloading devices may only benefit certain patients, depending upon their activity, and may contribute to reduced cardiovascular health. A personalized approach is needed.

High Acceptance and Adherence to Wearing the Device

Clearly, offloading devices that are not worn cannot protect the plantar DFU from the mechanical loads that considerably impair healing. Multiple high-quality trials have demonstrated healing outcomes are superior in NRKHDs compared with removable knee-high devices ⁴⁵ despite each device is known to reduce PP to a similar degree, ⁴⁵ thus attributing different healing outcomes to the low adherence found when wearing the removable devices.^36,46-48 Interestingly, offloading acceptance has received much less attention than adherence, especially considering we need to maximize both acceptance to initiate the treatment and adherence during the treatment. Broadly speaking, removable devices are associated with high acceptance but low adherence, and non-removable devices are associated with low acceptance but high adherence. Similar to PP, shear stress, and weight-bearing activity, the acceptability and adherence to the same device is likely to vary between people, depending on their personal health and circumstances.

Proposed Personalized Approaches to Offloading DFUs

Prescribing the same NRKHD to all patients uses the (incorrect) assumption that all patients have the same magnitude of need to reduce PP, shear, and weight-bearing activity, plus, the same magnitude of need to adhere to the device. As discussed, this results in lower acceptance of the treatment. In contrast, a personalized approach where offloading treatments are designed to balance the individual’s personal circumstances, preferences, and actual offloading needs to achieve effective healing would be welcomed by both patients and clinicians. We propose three key personalization approaches to contribute to improved offloading treatments, these include developing modular devices, advanced manufacturing techniques and materials, and incorporation of sensors in “smart devices.”

Modular Devices Enable the Key Mechanical Device Features to Be Added/Removed

The utilization of modular devices may be readily achievable in the near future via methods of developing innovative and dynamic designs. Such modular designs could enable increased (or even decreased) PP reductions by adding or removing key mechanical features of devices optimized according to each patient’s needs. An example of this might include a series of modular components including a base ankle-high offloading device, with components that are removable such as customized insole, rocker-bottom sole, and knee-high cast walls, along with adjustable controlled ankle motion components. In the initial treatment period, it may be necessary to include all these components in the patient’s device to establish optimal PP, shear, and activity reductions to accelerate ulcer healing in the early phase. As the treatment period progresses and accelerated healing becomes evident, components that most adversely affect the person’s gait could be removed, and thus improving acceptance and adherence which may also contribute to providing the same overall magnitude of plantar tissue stress reduction, as early studies have suggested.^18,41 Once nearly healed, the rocker bottom could be removed or the controlled ankle motion adjusted to be more flexible to enable a more normal gait in anticipation of rehabilitating the patient into a more sustained remission from ulcers. Later phases could see the wall component being removed entirely to more resemble therapeutic footwear needed for use in remission. Importantly, if the patient has a setback and requires an elevation in PP and activity reduction, then components could be re-added as needed until a more “normal” ulcer-healing trajectory returns. Such a modular device, in theory, should increase patients’ engagement in their own treatment considering the empowerment the patient would gain in determining the features that work best for their personal circumstances and healing trajectory. There are some devices available where device features can be added and removed. For example, the Stabil-D (Podartis, Montebelluna, Treviso, Italy) is an above-ankle offloading device where ankle stabilizer inserts and parts of the insoles can be added or removed. ⁴⁹ Another example of a modular device is the PulseFlow DF® (The Diabetic Boot Company, Ltd., UK) where the lower leg part of the device can be added or removed from the footwear part. ⁵⁰ These devices allow for a modular approach to offloading as described above; however, future studies should investigate the effects of these and more advanced modular offloading devices on foot ulcer healing.

Advanced Manufacturing Enables Personalized Device Designs

Three-dimensional (3D) scanning, computer-aided design, and 3D printing are already used in the manufacture of personalized foot orthoses and ankle-foot orthoses, ⁵¹ and will enable new approaches to personalize offloading devices to improve effectiveness and acceptance. Starting with the 3D scan of the leg and foot, it is possible to design and 3D print a personalized offloading device that very closely contours the leg with a similar load sharing mechanism to the lower leg as occurs in knee-high devices, and closely contours the foot improving distribution of PP. The 3D scanning is valid and reliable for scanning the foot and leg, while also being significantly faster than traditional casting.^52,53 Furthermore, designs can be optimized to address reasons for non-acceptance raised by patients and clinicians. For example, heavy and bulky designs, ¹¹ which are strongly associated with the low adherence levels for using knee-high offloading devices,^48,54 can be made lighter with built-in porosity and channels which enable air flow, and if printed with waterproof materials, can be easily washed. The freedom of design afforded by 3D printing and computer optimization make it possible to produce offloading devices to be sufficiently strong while minimizing weight and bulk as already seen in ankle-foot orthoses which were manufactured to reduce the weight while increasing the stiffness of the device.^51,55 Existing knee-high offloading devices can be hot to wear. ²⁰ Already, 3D-printed ankle fracture casts and cervical orthoses with improved ventilation have been designed to improve patient comfort^56,57 which could easily be translated to offloading device design. Hence, it may be possible to create a personalized device from a 3D scan that is lighter, has improved ventilation, and effectively reduces plantar tissue stresses. A further major benefit of a digital workflow is that the 3D digital model can be re-visited and manipulated, modules can be added, colors and designs can be changed, and the patient can be involved in the co-design process to improve satisfaction with aesthetics.

In addition to addressing barriers to offloading use, the personalization enabled by advanced manufacturing technologies could improve the mechanical effectiveness of offloading. Computer-aided optimization techniques could allow automated design of devices that most effectively reduce PP. Several processes including optimizing algorithms and patient-specific finite element models have been proposed to optimize the shape and mechanical properties of insoles to reduce PP for DFU prevention.^58-60 Furthermore, 3D printing also allows the manufacture of flexible mechanical metamaterials that have complex geometric internal architectures with advanced mechanical properties and functionalities. ⁶¹ These mechanical properties, including stiffness, can be “tuned” by adjusting the internal structure, enabling the design of devices with mechanical properties that vary throughout.^58,62 It is even possible to create metamaterials with behaviors that reduce stiffness or change shape in real-time in response to elevated loads ⁶¹ ; such a material could potentially allow pressure thresholding, whereby parts of an insole could responsively become less stiff if pressure exceeds a predetermined threshold. Insoles within future personalized devices could not only be contoured to the foot but also have optimized and variable mechanical properties across the shape to improve offloading effectiveness via tuning 3D printing structures.

Smart Devices Incorporating Sensors Provide Feedback to Patients and Clinicians to Optimize Plantar Tissue Stress

Early research suggests it may be possible to establish a baseline combined plantar tissue stress measure, made up of PP, shear, weight-bearing activity, and adherence. ¹⁷ Such a measure could be “tuned” by adjusting different combinations in PP, shear, and activity reduction magnitudes to suit the offloading needs of the individual patient, while engaging the patient to be highly accepting and adherent to such offloading treatment.^17,41 There is currently no evidence-based algorithm available to adjust offloading devices based on the individual patient’s parameters, although some guidance is provided by previous studies analyzing how adjustments of, for example, footwear reduce PP at different plantar locations.^63-65 For example, such algorithms suggest that the combination of replacing the insole’s top cover and cushioning the insole locally effectively reduces PP under the metatarsal heads.^63,64 The development of such evidence-based algorithms for individual adjustments of devices to reduce PP at foot ulcers is an important topic for future research. Real-time feedback using “smart insoles” or similar devices with incorporated sensors that measure PP, activity, and adherence are already becoming available and showing promise in changing patients offloading treatment behavior.^66-70 For example, the SurroSense Rx intelligent insoles system (Orpyx Medical Technologies, Calgary, Canada) provides feedback on PP to patients via a smartwatch to help facilitate the patient to change their behavior regarding their weight-bearing activity and in turn potentially reduce reulcerations.^66,67 Similarly, the SmartBoot (Sensoria Health Inc., Redmond, WA, USA) provides feedback on adherence to the patient via a smartwatch. ⁷⁰ Furthermore, patients’ awareness of adherence monitoring with a temperature sensor (Orthotimer, Balingen, Germany) can in itself result in higher adherence. ⁶⁸ For a patient in need of reducing plantar tissue stress to heal a DFU, measurements of PP, activity, and adherence could be made continuously during the treatment period to establish if their combined plantar tissue stress is being maintained below a personalized threshold. If not, the patient and clinician can collaborate on solutions how to optimize each factor to reduce the plantar tissue stress to a level that promotes healing of the DFU. In short, clinicians will soon no longer be reliant on the patients’ self-reported measures of pressure, activity, and adherence, but are now on the cusp of being able to work with their patients to objectively measure and dose their patients’ various factors that work best for them and also most effectively heal their ulcer. The progress in the field of sensors and remote monitoring in diabetic foot management is reviewed in more detail elsewhere.^71,72

Personalized Offloading Is More Than Technology

In addition to the technical solutions proposed above, other means may need to be used to personalize offloading and optimize plantar tissue stress. For example, highly active DFU patients may need to cut down on weight-bearing physical activity, and therefore need to be put on sick-leave or recommended to change to less weight-bearing work duties, thereby reducing plantar tissue stress. Furthermore, to achieve a satisfactory level of acceptance and adherence to using the device, personalized device designs and sensors providing feedback on adherence to patients may need to be complemented with other interventions. This can include the use of different educational techniques, such as, motivational interviewing, ⁷³ patient-centered communication, ⁷⁴ and shared decision-making, ⁷⁴ to strengthen patients’ motivation for adherence. It may also be useful to, at clinical appointments, measure and provide feedback to patients on PP,^75,76 weight-bearing activity, ⁷³ and ulcer healing. ⁷⁷

Conclusions

Offloading is one of the most important interventions to heal plantar DFUs. ³ Strong evidence exists for the use of NRKHDs, ⁴⁵ but clinical uptake of these gold-standard devices remains low.^4,8-12 In this article, we have discussed how a personalized approach to offloading DFUs may be a fruitful future solution to this dilemma. A personalized approach would focus less on using a specific type of device, and more on how to individually optimize the mechanisms that bring about ulcer healing, that is, pressure and shear on the DFU, weight-bearing activity, patient acceptance, and adherence. This approach is more in line with what clinicians currently try to do subjectively, but remain unsupported by scientific evidence or theoretical frameworks. High-quality trials for each proposed personalized treatment option are ideal but often slow to produce. In the meantime, the frameworks of the personalized medicine approach and plantar tissue stress concept, ¹⁷ provide a potentially faster way forward for studies to inform clinical practice.

A number of proposed future personalized offloading treatment options are emerging. First, modular designs of offloading devices would allow clinicians to tailor the device design to different patients’ needs and preferences, and also adapt the design to a single patient during different phases of the treatment period. Research is needed on how different device features (rocker sole, high cast walls/struts, etc.) in isolation or in combination affect PP, shear, activity, acceptance, and adherence. Second, advanced production techniques and materials need to be studied to see whether these approaches can result in more attractive devices (less bulky, heavy, hot, etc.) with similar or better reduction of plantar tissue stress than currently available devices. Third, a large opportunity exists to incorporate sensors that provide real-time feedback to patients, which is a promising approach to further optimize personalized offloading treatments and to empower patients and improve their quality of life.