Mini-Review: Tendon-Exposed Wound Treatments

Abstract

Background

Tendon-exposed wounds are complex injuries with challenging reconstructions and no unified treatment mode. Furthermore, insufficient tissue volume and blood circulation disorders affect healing, which increases pain for the patient and affects their families and caretakers.

Review

As modern medicine advances, considerable progress has been made in understanding and treating tendon-exposed wounds, and current research encompasses both macro-and micro-studies. Additionally, new treatment methods have emerged alongside the classic surgical methods, such as new dressing therapies, vacuum sealing drainage combination therapy, platelet-rich plasma therapy, and live-cell bioengineering.

Conclusions

This review summarizes the latest treatment methods for tendon-exposed wounds to provide ideas and improve their treatment.

Keywords:

• Tendon-exposed wounds
• refractory wound
• wound healing

Background

In recent years, tendon-exposure trauma has become an increasingly common clinical problem owing to lifestyle changes and increased incidences of traffic accidents, mechanical injuries, burns, and diabetes (thus diabetic foot), making it a popular clinical research topic.¹ Tendon explant repair is a complex biological process with a challenging treatment and extensive recovery time, which psychologically and economically burdens patients and their families.² Globally, between 0.45 and 3.33% of the population has a history of leg ulcers,³ and an estimated £8.3 billion was spent in the United Kingdom in 2018 to assess and treat 3.8 million people with wounds, which is a considerable drain on healthcare resources.⁴ Tendons lie directly beneath the soft tissue; thus, areas with less soft tissue coverage, such as the back of the hands and feet, are highly susceptible to tendon outgrowth wounds following skin defect or necrosis. Since tendons are fibrous connective tissues with a relatively poor blood supply, they are mainly nourished by synovial fluid from the synovial tendon sheaths rather than by vascular perfusion. Consequently, once a large skin defect has formed, self-healing of the tendon is difficult, and it is prone to infection, often requiring clinical intervention.^5,6

Modern medicine offers various approaches for treating exposed-tendon wounds, and as the global population ages, medical practitioners are placing more emphasis on this area of research, which has expanded beyond the macroscopic level into the microscopic level. Therefore, this ­article reviews the latest advances in treating exposed-tendon wounds.

Review

Physiology of Wound Healing

Physiologically, wound healing is roughly divided into four dynamic processes: platelet aggregation, inflammation, cell proliferation, and remodeling. Each segment is continuous and overlapping,⁷ and complex interactions between various cell types, biomolecules, and the extracellular matrix (ECM) work together to produce inflammatory responses, synthesize granulation tissue, and restore the epithelium (Figure 1).^8,9

Figure 1. Pathophysiological mechanisms in the pathogenesis of tendon exposed wounds. The mechanisms include bacterial infection, poor vascularization, insufficient growth factors and lack of repair cells.

Common wounds usually undergo timely progression from the inflammatory phase to the end of the remodeling phase, but each healing stage is delayed or stagnated for tendon-exposed wounds, delaying overall wound healing and making self-healing difficult.¹⁰ Tendon exposed wounds are chronic wounds and the treatment can be very tricky.^11,12 Adequate debridement and establishment a healthy granular bed is a critical step to healing.¹³ And it is a prerequisite for numerous specific clinical interventions. In fact, the healing process of tendon exposed wounds has its own unique characteristics comparison with dermal wound repair as follows: firstly, because of the lack of blood flow to the tendon itself, the possibility of tendon necrosis after prolonged exposure is a concern. At the same time, the difficulty of local granulation tissue growth in the tendon wound leads to a higher rate of necrosis in the skin graft or flaps compared to the dermal wound.¹⁴ Secondly, tendon exposed wounds are difficult owing to the poor local blood supply, a lack of relevant GFs, and wound infection. Meanwhile tendons have a relatively poor blood supply since they are composed of fibrous connective tissue, which can be exacerbated by trauma and basal blood supply disorders; thus, granulation tissue formation is ineffective. Moreover, surgical procedures to repair the trauma, such as skin grafting, local flaps, or free skin grafts, put the tissue cells in a perpetual state of ischemia and hypoxia, so they cannot obtain nutrients or accumulate metabolic products. Consequently, skin grafting and flap surgeries have a high failure rate.^5,6 Thirdly, lacking quantities and reduced activities of relevant GFs affect wound healing. Numerous GFs promote cell proliferation and vascular regeneration, accelerate tissue epithelialization, and regulate fibroblasts, accelerating wound healing. However, in tendon-exposed wounds, low concentrations of GFs severely hinder wound-healing processes.¹⁵ Finally, wound infection slows the healing process. The skin is the body’s most important barrier against the outside world, and breaks in the skin leave the wound highly susceptible to bacterial infection, severely hindering the healing process by releasing various toxins and enzymatic substances. If the infection is severe and cannot be contained via the immune system or antibiotic treatment, long-term persistent damage to the wound will keep it in the inflammatory phase, prolonging or stalling healing.^16–18

General Treatment of Tendon Outgrowth Wounds

Exposed tendon wounds can be treated according to the TIME principles: tissue debridement, infection control, moisture balance and wound margins.¹⁹

Debridement

Debridement is now considered a core component of wound care.²⁰ According to Williams et al. studies, aggressive debridement significantly improves the likelihood of chronic wound healing.²¹ Debridement is the removal of dead cells, leaving only viable tissue. In fact, all layers need to be carefully explored without a tourniquet when treating the wound in order to observe the tissue blood supply. A 2–3 mm excision of the skin around the tissue, as well as all damaged and contaminated soft tissues, is generally considered.^22,23 When tendon component resection is required, the need for additional surgical treatment should be determined by whether the extent of tendon resection has an impact on motor function. We consider tendon suturing or other treatment only when the extent of resection is too large and affects the motion of the affected limb. Finally, the wound should be flushed with plenty of saline and pulsed irrigation is recommended to further reduce the risk of infection. For optimal healing, the first debridement operation should be performed within 6–12 h after the injury. Finally, soft tissue coverage should be planned in the form of a phase I procedure (e.g., suture, skin graft, or flap) or a phase II procedure (e.g., vacuum-assisted suture [VAC], PRP, or a new dressing), depending on the intraoperative wound condition, should be considered. If the wound is severely contaminated or infected, consider a subsequent secondary debridement operation or repeat debridement every 48–72 h until the wound is clean.^13,15

Antibiotic Therapy

In addition to surgical debridement, the wound should be treated prophylactically with intravenous antibiotics. Numerous reports have noted a significant reduction in wound infection rates in patients who received antibiotic prophylaxis compared to the treatment group that did not receive antibiotic prophylaxis, and it is believed that an important factor in reducing infection rates is the early use of antibiotics.^24–26 Despite the importance of antibiotic therapy in wounds, there are still no specific guidelines. In most cases, we consider antibiotic therapy starting with cephalosporins followed by sensitive antibiotics after culture results are obtained.

Moisture Balance

Related studies point out that moist wounds heal faster and have less risk of infection. If the wound appears dry, a dressing will need to be added to retain moisture.²⁷Wound edges need to be kept flat. If the edges are rolled up, they need to be properly excised to promote epithelialization.²⁸

Flap Transplantation

The skin flap method is a classic surgical technique for repairing skin and soft tissue defects caused by congenital or acquired trauma.^29,30 Autologous flap transplantation has strong anti-infective properties, good histocompatibility, high softness, and key roles in functional reconstruction. However, the primary features of tendon-exposed wounds are soft tissue loss and tendon exposure. Thus, these wounds have local fibrous connective tissue areas with relatively poor blood supply to the wound base, which is not suitable for simple closure or separate skin transplantation. Even if these defects are minor, the reconstruction survival rate is low,³¹ likely because immediate debridement of tendon-exposed wounds does not provide a suitable wound bed for successful flap transplantation. Successful flap transplantation requires the formation of a healthy granulation tissue bed at the base of the wound. However, wound healing additives, such as GF-rich dressings,^32,33 matrix protein substrates,³⁴ hyperbaric oxygen,³⁵ skin substitutes,³⁶ and wound healing techniques (e.g., negative pressure drainage), can promote granulation tissue formation on the tendon’s surface.^37,38

There are many types of flaps, and appropriate flaps and surgical methods should be selected for repairing wounds of different parts and depths. According to Marchesi’s summary of flap grafting for Achilles tendon exposed wounds, we can get inspiration: when the tendon exposed wound diameter (<2 cm) is Small defects, local rotational flaps or V–Y advancement flaps can be considered to complete the surgery quickly; when the wound diameter (2–4 cm) is moderate defects, it is necessary to use propeller perforator flaps or bipedicled flaps to minor donor site morbidity and ensure the blood supply of the flap; when the wound diameter (4–8 cm) is large defects, in the absence of contraindications, it is mostly necessary to treat with microsurgical assistance to ensure the normal blood supply of the flap; finally, when the wound diameter (>8 cm) is very large defects, the use of a latissimus dorsi flap may be considered.¹³ For instance, tendon adhesion in the later stage limits skin grafting for full-thickness skin defects with tendon exposure. However, Carty et al. reported that applying a fasciocutaneous flap in a local defect wound of an exposed hand tendon was a good choice for preventing postoperative tendon adhesion.^39,40 Straub et al. also used platelet-rich fibrin (PRF) as a lubricating layer to protect skin grafts from tendon movement.³² Moreover, the postoperative survival of the flap depends on the abundance of oxygenated blood at the flap’s distal edge. Therefore, when the wound exceeds a certain size, it is difficult to achieve satisfactory results by simply covering it with a single large flap, especially for tendon-exposed wounds. For such problems, endovascular interventional therapy has long been used in flap transplantation, with obvious advantages and a wide application.³¹ For example, Li et al. reported the successful application of a chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral femoral muscle flap to repair a large area of deep wounds in the ankle, noting that this was an effective and relatively safe method.⁴¹ Similarly, Martin et al. reported the successful repair of an open wound with an exposed right forearm tendon using a flap by anastomosis of the radial artery.⁴²

In addition, the skin flap is generally accompanied by subcutaneous soft tissue, and there are apparent scars and other problems after healing. Therefore, the autologous skin flap may not meet the patients’ long-term functional and esthetic needs when it comes to hand and foot tendon exposure wounds. However, one study suggests that autologous dermal transplantation using the vacuum-assisted closure (VAC) system is an effective alternative for small, shallow wounds with surrounding tissue damage that cannot form a local flap.^43,44 They reported that the technique is simple, fast, and inexpensive and successfully repaired soft tissue defects of the Calf, foot, and toe. Similarly, in recent years, perifascial areolar tissue (PAT) has been commonly used in the wound surrounding the damaged tissue in tendon-exposed wounds.⁴² PAT refers to very thin, loose connective tissue on the deep fascia rich in blood supply due to the many vascular plexuses, and it has great advantages for healing wounds exposed to rigid structures, such as tendons.⁴⁵ The autologous flap is advantageous due to the rich blood supply, wear resistance, and lack of immune rejection. However, there are also well-known limitations, such as an insufficient flap donor area, immense surgical trauma, and postoperative appearance.⁴⁶

Adjunctive Treatment of Tendon Outgrowth Wounds

With advances in modern medicine, various techniques and materials have emerged to adjunctive treat exposed-tendon wounds, improve flap survival rate. In addition to the classic combined vacuum sealing drainage (VSD) therapy,⁴⁷ Platelet-rich plasma (PRP) therapy,⁴⁸ new dressings,⁴⁹ and cell therapy⁵⁰ have emerged. The following sections review the latest adjunctive treatment advances for tendon explants to provide ideas and treatment assistance.

Artificial Skin Combined With VSD

Developments in tissue engineering technologies have resulted in artificial dermal substitutes that effectively repair tendon-exposed wounds.^51–55 Applying an artificial dermis to soft tissue defect wounds overcomes the dependence of traditional flaps on autologous soft tissue, solves the problem of an insufficient supply of autologous skin, and is richly available. Moreover, the surgical method is simple and easy, the surgical trauma is minimal, and the postoperative limb function and appearance are greatly improved.^48,52 However, the artificial dermis alone may not quickly achieve sufficient granulation for tendon-exposed wounds, making the wound very susceptible to bacterial infection.⁵⁶

Many recent studies have demonstrated that negative pressure VSD can timely remove wound exudates, inhibit bacterial colonization, reduce tissue edema, increase local blood perfusion, and promote cell proliferation and the formation of protein synthesis factors.^44,57,58 Therefore, it is common to use an artificial dermis combined with VSD to reconstruct tendon-exposed wounds.^{36,46,58–60} For example, Zhu et al. used negative pressure VSD combined with an artificial dermis to successfully treat 36 cases of tendon and other structurally exposed wounds, shortening the patient’s hospitalization time with satisfactory curative effects.⁶⁰ Similar alternative VAC methods on the artificial dermis can also successfully repair soft tissue coverage of complex wounds in the foot and ankle.⁵⁸ However, successful tissue engineering requires a trinity of scaffolds, cells, and a rich environment.⁴³ Artificial dermis grafts have the scaffold function of vascular reconstruction and collagen formation, which allows fibroblast-like cell, macrophage, and lymphocyte migration and ingrowth and promotes capillary ingrowth.^51,55 At the same time, VSD provides a certain degree of mechanical force for wound healing, resulting in better attachment of the artificial dermis’ collagen layer to the wound. Sufficient attachment accelerates the process of fibroblast crawling and vascular ingrowth in the collagen layer of the artificial dermis, promoting dermis formation and vascularization of the wound, which creates a suitable wound bed for autologous grafts. Lee et al. provide an example of this; they used dermal substitutes and negative pressure wound therapy to treat hardware-exposed soft tissue defects.³⁶ Another report suggested that simple skin transplantation with many flaps had high tendon adhesion rates and noted that artificial skin had a considerable advantage for tendon sliding after reconstructing tendon-exposed wounds.⁵³

Although an artificial dermis combined with VSD has advantages for repairing tendon-exposed wounds, there are also apparent deficiencies. As a blood-deficient tissue, the tendon must form a sufficient wound bed before secondary autologous skin transplantation is possible, and it can take two to four weeks to form sufficient granulation tissue.^51,53 Thus, the total treatment time is relatively long. Additionally, the artificial dermis is a tissue engineering product that is relatively expensive. These disadvantages may be a psychological and economic burden for some patients.^47,52

Platelet-Rich Plasma (PRP) and Other Blood-Related Products

PRP is an autologous serum obtained by centrifugation and separation of whole blood in vitro with a platelet concentration higher than that of standard plasma.⁶¹ Hematologists first introduced this concept in 1970 for the main purpose of treating thrombocytopenia.⁶² However, studies have shown that PRP is rich in GFs, chemokines, and cytokines, so many researchers have a strong interest in the potential of PRP in regenerative medicine.⁶³ PRP has been widely used in dermatology, plastic surgery, sports medicine, and oral and maxillofacial surgeries, amongst other disciplines.⁶⁴ Many studies have demonstrated the beneficial effects and encouraging patient outcomes of PRP therapy in clinical practice (Figure 2).^63,65,66

Figure 2. Mechanisms of PRP for tendon exposure wounds. PRP promotes the secretion of growth factors of PDGF, egf other growth factors. At the same time, it inhibits the inflammatory response and reduces the production of local ROS. Finally, these cytokines act on MSCs, macrophages fibroblasts, etc., and ultimately promote wound healing by means of inflammatory responses, proliferation and remodeling.

Moreover, PRP has certain advantages for refractory wound healing (e.g., tendon-exposed wounds); for example, they promote faster wound healing.^64,67,68 In addition, platelet alpha-particles are rich in GFs, such as PDGF, insulin-like growth factor (IGF) 1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal GF, and TGF-β1.⁶⁹ These are hypothesized to stimulate cell proliferation and migration, angiogenesis, granulation tissue formation, and ECM production, thus involving the entire wound healing process.⁷⁰ However, the tendon belongs to fibrous connective tissue and has no abundant blood supply, leading to a relatively low GF level. Furthermore, effective healing becomes difficult once a skin defect occurs above the tendon. Therefore, applying PRP in these and other fields can induce supraphysiological levels of GF to theoretically stimulate the regression of chronic pathological processes.

As previously mentioned, platelets are the first cells to respond in wound healing, initiating wound reconstruction. Platelets activate once a clot has formed, releasing GFs from the alpha-particles to stimulate healing.^62,71 Like many cytokines, GFs bind ligands to related cell surface receptors, and then the membrane surface receptors change to transmit signals to the cell. These changes promote the phosphorylation and activation of specific protein kinases in cells, eventually leading to the translocation of phosphorylated kinases to the nucleus. This phosphorylated transcription factor enables the transcription and translation of wound healing-related target genes that ultimately perform coding functions.^61,72

The primary roles of various GFs differ, but in general, the goal is to coordinate wound healing. For example, PDGF initiates callus formation through fibroblast and mesenchymal stem cell (MSC) proliferation and wound chemotaxis.⁷³ PDGF is also important in promoting endothelial cell proliferation in granulation tissue and angiogenesis.⁷⁴ VEGF, corresponding to its name, strongly stimulates vascular endothelial cell proliferation, thereby participating in neovascularization.⁷⁵ TGF-β stimulates MSC proliferation and differentiation and contributes to ECM formation through collagen production; it also helps mediate angiogenesis.^76–78 enhances endothelial and fibroblast migration and mitosis, stimulates angiogenesis and collagen formation, and has an important effect on tissue repair.⁷⁹ Finally, IGF stimulates cell growth and proliferation to promote wound healing.⁸⁰

Although numerous studies have shown that GFs in PRP are beneficial for reconstructing refractory wounds with tendon exposure,^64,69,81 other components, such as pro-inflammatory cytokines, have a negative impact.⁸² For example, IL-1β plays an important role in cartilage damage and osteoarthritis and has been used to induce osteoarthritis in animal models.⁸³ Similarly, other inflammatory factors, such as TNF-α, induce cartilage damage and inhibit cartilage progenitor cell migration when it interacts with IL-1β, eventually leading to delayed cartilage healing. Furthermore, these inflammatory factors play a role in wound pain. Therefore, applying PRP to the joints may accelerate cartilage decomposition due to the pro-inflammatory reaction, ultimately inducing articular cartilage injury nonunion or aggravating existing arthritis.⁷⁰

In recent years, the effects of PRP on tendon-exposed wound healing have been verified in humans.^84,85 For instance, Cervelli et al. used plasma and hyaluronic acid-binding gel in Achilles tendon-exposed wounds, finding that wound severity significantly decreased compared to the control group, almost all patients achieved wound closure, and no infections were recorded during the treatment.⁸¹ Additionally, our group have performed a clinical study that included 12 patients (average age: 42 years) with tendon exposure due to soft tissue defects of various causes.⁴⁸ After fully debriding the patient’s wound, venous blood was extracted to obtain PRP by centrifugation. Then, the PRP was sprayed on the wound to form an autologous platelet gel, and healing was assessed based on the granulation tissue’s appearance and the wound’s size reduction. Overall, wound healing was observed in all patients, pain and serous discharge decreased within one week of treatment, and no side effects were observed throughout the follow-up period. Compared with other autologous cell therapies, the main advantage of using platelets as a regenerative agent in wound healing is that they can be extracted directly from the patient’s venous blood. Thus, PRP is readily available, has a high degree of safety, and has no possibility of immune rejection or blood-borne disease transmission. Moreover, it is simple to obtain and administer, does not require advanced preparation facilities, and can reduce postoperative pain and swelling.

In recent years, other blood-derived products have also been used to cover skin wounds,^86–88 for example, leukocyte- and PRF (L-PRF), which is a second-generation platelet concentrate for local use rich in fibrin, platelets, and white blood cells. It can also be obtained quickly and at a low cost without requiring activators and anticoagulants. Reports also indicate that L-PRF positively affects chronic ulcer wounds, and in vitro studies demonstrated that L-PRF exerted a very strong positive effect on the proliferation of all tested cell lines, especially fibroblasts and keratinocytes.^87,89 Therefore, PRP and other blood products are generally advantageous for wound healing.

New Dressings

Wound dressings influence and accelerate the healing process,⁴⁹ and the types of wound dressings have advanced in recent years. Traditional dressings such as mainly gauze, cotton pads and bandages, are still widely used in clinical practice due to their low manufacturing costs and simplicity. However, these dressings have considerable disadvantages, such as poor wound moisturization, poor hemostasis, and a tendency to adhere to exudate, resulting in pain and new soft tissue defects during dressing changes. Therefore, modern dressings may be a more appropriate option.

Compared to conventional dressings, modern dressings encourage a moist environment for wound healing and have better biocompatibility and degradability, significantly affecting wound healing. Modern dressings commonly used in clinical practice include hydrogels, foams, cell-free matrices, and honey. For example, absorbable gelatin sponges combined with polyurethane membranes for refractory wounds with bone or tendon exposure is a novel and cost-effective wound reconstruction method.⁹⁰

A wide variety of novel dressings have been reported. To date, the literature has reported that honey, silver ionomer, and cell-free matrix dressings are most applicable for refractory wounds, which include tendon exposures. Firstly, honey has long been used as a wound dressing worldwide. Honey contains many bioactive components that promote wound healing through four stages: hemostasis, inflammation, proliferation, and remodeling.^91,92 For example, Ahmed et al. recently reported a positive wound healing effect and confirmed the antibacterial and anti-inflammatory effects of honey,⁹³ reporting that the anti-inflammatory effect reduced edema and abnormal wound secretions and thus reduced the time to establish a clean wound bed. In addition, the bioactive substances in honey stimulate cell proliferation, collagen synthesis, and vascular and granulation tissue formation, all of which accelerate wound epithelialization and, thus, wound contraction, which facilitates wound healing and reduces the healing time. Honey also has antibacterial properties; its high viscosity protects against infection and reduces the wound’s bioburden.⁹⁴ Some have even noted pain relief and debris removal from wounds after applying honey.

Secondly, Loh et al. demonstrated the clinical efficacy of silver ionomer as a wound dressing for tendon-exposed lower limb wounds,⁹⁵ which provided a wet environment for the tissue defect, offering effective protection of the exposed tendon while absorbing wound exudate and promoting granulation tissue growth, resulting in safe and effective wound healing. Silver also has known antibacterial effects; silver ions in the dressing are oxidized upon contact with the wound, forming active silver ions. These ions interfere with bacterial function by chemically reducing or inactivating the biological activity of enzymes, inhibiting bacterial division, or directly killing the bacteria on the wound’s surface.^96–98

Finally, cell-free matrix dressings have been recently reported and well-received.^99–101 For example, Melandri et al. reported the excellent performance of a new human-derived cell-free dermal matrix for treating tendon-exposed distal lower limb wounds, suggesting this is a promising alternative for covering tendon-exposure wounds.¹⁰² However, the function of these dressings is similar to that of other dressing types, mainly to promote granulation tissue formation and wound epithelialization and provide a moist environment for the wound. Therefore, new dressings offer several options for treating tendon-exposure wounds.

Live-Cell Bioengineering

Some products contain live cells, such as live adipose stem cells, fibroblasts, and dermis in combination with epidermal cells. Applying one or several types of live cells is an important point of differentiation between this method and the above-mentioned reconstruction methods. Hefton et al. and Leigh et al. were the first to describe the application of cultured epidermal sheets for treating skin defects,^103,104 reporting that they healed or improved most soft tissue defect wounds and reduced the length of the patient’s hospital stay. Similarly, Jaime et al. concluded that frozen human allogeneic epidermal cultures were safe and effective for treating patients with tendon-exposure wounds, and they might apply to any lower limb skin defect.¹⁰⁵ However, in their study, all wounds were treated with a combination of VAC therapy and deepidermalized implants; as a result, they formed granulation tissue within a certain period postoperatively. Consequently, the exposed structures were effectively and adequately covered, and none of the patients’ wounds were infected. Therefore, sufficient granulation tissue and a clean wound surface created a suitable wound bed for the additional reconstructive treatments.¹⁰⁶ Nonetheless, tissue cultures are usually kept in a sterile environment and can directly cover the soft tissue defect after thawing; therefore, this method is simple, convenient, and free from donor complications.

Viable cryopreserved human placental membranes (vCHPM) are another effective wound coverage method.^107,108 vCHPM contains natural components of the tissue that remain intact, including a structural matrix, GFs, and a natural mixture of endogenous live cells, including MSCs. The collagen-rich ECM also provides a structural scaffold for cell migration, proliferation, and differentiation, which is required for tissue repair, and the accompanying GFs and various cell types form a suitable basal bed for abnormal wounds. Suzuki et al. reported positive effects of vCHPM for managing complex wounds characterized by hardware, such as exposed tendons (Figure 3).¹⁰⁹

Figure 3. Treatment of tendon exposed wounds. Treatment options for exposed tendon wounds include: flap grafting, artificial skin combined with VSD, platelet rich plasma and other blood-related products, new dressings, and so on.

In summary, these approaches make it apparent that non-surgical treatment options promoting outpatient-based anatomical and functional tissue replacement without donor site complications are necessary to maximize the patient’s chances of recovery and mobility.

Conclusions

Exposed-tendon wounds are commonly found on the dorsal surface of the hand and foot, where impaired blood flow, a relative lack of GFs, and infection make wound reconstruction difficult, considerably affecting the patient’s quality of life. Consequently, healing such wounds is one of the most important challenges in medicine. This short review briefly outlines the treatment advances for tendon-exposed wounds, including flap grafts, VSD combined with an artificial dermis, PRP and other blood-related products, novel dressings, and live-cell bioengineering, as well as describes the biological process of general wound recovery. Although the evidence for these new therapies is limited, they all have encouraging clinical data supporting their use as new therapies.

Authors’ contributions

ZD and ZSL wrote the manuscript. GC prepared the reference, data. All authors reviewed the manuscript and approved the final version.

Ethical approval

This article is a review and should not be reviewed by the ethics Committee.

Informed consent

Informed written consent was obtained from the patient to publish their personal or clinical details information.

Abbreviations
ECM	=	Extracellular matrix
FGF	=	Fibroblast growth factor
GF	=	Growth factor
IGF	=	Insulin-like growth factor
IL	=	Interleukin
L-PRF	=	Leukocyte- and platelet-rich fibrin
MSC	=	Mesenchymal stem cell
PAT	=	Perifascial areolar tissue
PDGF	=	Platelet-derived growth factor
PRF	=	Platelet-rich fibrin
PRP	=	Platelet-rich plasma
TGF-β	=	Transforming growth factor-beta
TNF-α	=	Tumor necrosis factor-alpha
VAC	=	Vacuum-assisted closure
vCHPM	=	viable Cryopreserved human placental membranes
VEGF	=	Vascular endothelial growth factor

Acknowledgments

Not Applicable

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data used or analyzed during this study are included in this published article.

Additional information

Funding

This study was supported by the Natural Science Foundation of China [Grant No. 32060222] for data collection costs.