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Biological Scaffolds from Placental Membranes: A New Frontier in Wound Care and Tissue Engineering

The following article explores the use of amniotic chorionic membrane, particulate scaffolds, and autograft transplantation in musculoskeletal injury healing, comparing their mechanisms, advantages, and clinical potential.

Biological Scaffolds from Placental Membranes

Written by

Angel Rigueras

Pain Management Specialist

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Written by

Angel Rigueras

Pain Management Specialist

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Table of content

Table of Content

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Musculoskeletal injuries encompass both acute and chronic damage to muscles, tendons, ligaments, peripheral nerves, joint structures, bones, and associated vasculature, often presenting as pain, stiffness, swelling, or functional impairment. These conditions afflict millions worldwide, frequently necessitating surgical intervention, immobilization, pharmacotherapy, and prolonged rehabilitation to restore mobility and quality of life. In the United States alone, work-related musculoskeletal disorders generate an estimated $45 to $54 billion in combined direct and indirect costs each year, reflecting a profound socioeconomic burden.

Initial management typically relies on non-surgical strategies—structured exercise programs, weight management, patient education, and physical therapy—to alleviate symptoms and improve function. Pharmacologic agents such as NSAIDs and acetaminophen can offer short-term pain relief, but neither reverse underlying tissue degeneration nor promote true regeneration, and their prolonged use carries risks of gastrointestinal, renal, and cardiovascular adverse effects. 

To address these limitations, regenerative musculoskeletal medicine has advanced markedly over the past decades, investigating biologic therapies designed to restore native tissue architecture and function. Biological sources fall into two primary categories:

  • Autologous therapies include platelet-rich plasma (PRP), bone marrow aspirate concentrate, and adipose-derived stromal vascular fraction (SVF). While these approaches deliver patient-derived cells and growth factors and have been associated with outstanding results, they can be related to certain inconsistencies, such as cell yields, heterogeneity in composition, and variable clinical outcomes. Standardized processing protocols and high-quality randomized trials are still in development.

  • Allogeneic perinatal tissues, notably amniotic–chorionic membranes, umbilical cord lining, and Wharton’s jelly. These off-the-shelf orthobiologics are rich in growth factors, anti-inflammatory cytokines, and extracellular matrix components, offering potent immunomodulatory and pro-regenerative cues without invasive harvest procedures

 

Emerging applications include tendon wrapping, cartilage scaffold seeding, and bone defect filling, positioning these biologics as promising tools to bridge the gap between symptomatic management and true tissue restoration in orthopedic care.

What Are Placental Membranes and Why Are They Important?

To understand the importance of using amniotic chorionic membrane, we need to know what it is and why it is important. Placental membranes are remarkable structures that protect and support the developing baby throughout pregnancy. These thin yet strong tissues surround the fetus and amniotic fluid, forming a barrier between the fetus and the outside world. Their multi-layered design and high collagen content give them a natural strength and flexibility, allowing them to absorb shocks and protect the fetus from physical harm.

But placental membranes do more than provide physical protection. They also act as a biological shield, preventing harmful bacteria from entering the womb. Their immune-regulating properties play a key role in keeping both the fetus and the reproductive tract healthy. Research has shown that these membranes have powerful anti-inflammatory and antimicrobial effects, which is why they are increasingly being used in medicine to help heal damaged tissues.

Additionally, placental membranes help regulate the volume and composition of the amniotic fluid, which is essential for the baby’s development. As pregnancy progresses, they also contribute to the natural process of childbirth by breaking down at the appropriate time.

 

The Layers of the Placental Membranes

Placental membranes are composed of two main layers: the amnion and the chorion, which are tightly joined together but serve different functions.

 

The Amnion: The Inner Shield

The amnion is the layer closest to the baby and the amniotic fluid. It is incredibly thin (only about 0.1 millimeters thick) but made up of five distinct layers that work together to provide strength, flexibility, and support.

  • The first layer is a single sheet of epithelial cells that directly contacts the amniotic fluid.

  • Beneath it lies the basement membrane, a strong support structure made of special proteins like collagen, laminin, and fibronectin.

  • The third layer, called the compact layer, is a dense mesh of collagen fibers that gives the amnion much of its strength.

  • Next is the fibroblastic layer, which contains special cells called amniotic mesenchymal cells (or fibroblasts) that help maintain the structure and produce the surrounding collagen.

  • The final layer, the spongy layer, acts as a cushion and allows the amnion and chorion to slide over each other. It’s rich in gel-like molecules called proteoglycans that help absorb movement and pressure from the growing fetus.

 

The amnion also contains a sugar molecule called hyaluronan, which makes it easier for cells to move around, a feature that’s particularly useful during wound healing.

 

The Chorion: The Outer Protective Layer

The chorion is thicker than the amnion (up to 0.4 millimeters) but not as strong. It also has a more complex structure, made up of three main layers:

  1. The reticular layer, closest to the amnion, is rich in collagen and proteoglycans and contains cells shaped like stars and spindles.

  2. The basement membrane, which connects and supports the upper layer, contains collagen and proteins that help keep the structure stable.

  3. The trophoblastic layer, made of several stacked layers of specialized cells, is the outermost part. It’s in close contact with the mother’s tissue and plays an important role in nutrient exchange and immune interaction.
Wound Care and Tissue Engineering

Healing Powers of Placental Membranes

What makes placental membranes especially exciting for modern medicine is their biological potential. Both the amnion and chorion have been shown to possess a range of healing properties:

  • Anti-inflammatory: They can reduce inflammation, which is essential for tissue repair.

  • Immunosuppressive: They help prevent harmful immune responses, especially important in transplant and graft procedures.

  • Antimicrobial: They naturally fight infection, reducing the risk of bacterial invasion.

  • Supports healing and growth: They release a mix of growth factors, cytokines (cell signaling molecules), and peptides that help tissues regenerate.

  • Prevents scarring: Their anti-fibrotic properties help minimize the formation of scar tissue.

  • Pain relief: Some studies suggest that these membranes can even help reduce pain.

 

Regulation of blood vessel growth: They can promote or inhibit the formation of new blood vessels depending on what the body needs.

Healing Faster and Better After Surgery

Clinical Application of Placental Membranes to Promote Wound Healing

In addition to accidental burns and trauma, millions of surgical wounds are created annually as part of routine medical procedures. Ensuring effective healing of both accidental and intentional injuries, while minimizing adverse aesthetic outcomes and promoting optimal tissue function restoration, is a central focus of clinical practice. While minor wounds typically heal without complication in healthy individuals, more extensive injuries or underlying conditions such as aging, infection, diabetes, vascular disorders, or cancer can significantly impair the healing process.

The amniotic membrane (AM), a component of the placental membrane, is a widely recognized biological material used in dermatology, ophthalmology, and surgical applications to support wound healing and tissue regeneration. Chorion, another placental membrane layer, has also demonstrated promising results, particularly in oral and periodontal surgery. AM possesses several beneficial biological properties, including anti-inflammatory, antimicrobial, anti-fibrotic, anti-scarring, and epithelialization-promoting effects, making it an ideal wound dressing.

AM has been extensively utilized as a biological scaffold due to its three-dimensional structure, mechanical support functions, and rich content of growth factors and cytokines. Both its cellular components and extracellular matrix contribute to the release of bioactive molecules (such as growth factors, cytokines, peptides, and soluble ECM components) that can interact with maternal tissues and promote regenerative processes.

Despite its well-documented therapeutic potential, the clinical use of placental membranes remains limited. Traditionally, AM is applied directly to wounds and secured using sutures, adhesives, or dressings. However, the membrane’s fragility, the need for fixation, and challenges associated with handling and positioning these thin sheets (combined with the high cost of using viable, cellularized tissue) have restricted its widespread adoption.

To address these limitations, novel AM-derived products have been developed, offering improved ease of production, storage, and application. These include hydrogel-based delivery systems containing solubilized AM, which facilitate more practical and efficient clinical use.

The clinical application of placental membranes dates back to 1910, beginning with skin grafts. By the 1940s, AM was being used in dermatology for treating burns and ulcers and in ophthalmology for conjunctival reconstruction. Since then, placental membranes have found utility in a broad array of medical specialties, including orthopedics, nerve regeneration, maxillofacial and oral surgery, chronic venous ulcers, and gynecological, obstetric, pulmonary, and fibrotic diseases.

While amnion is more frequently used in clinical settings, chorion has shown equal or even superior performance in oral and periodontal applications. Recent advances in hypothermic storage techniques have further improved the preservation of chorion’s structure and biological activity, enhancing its suitability as a regenerative scaffold.

Currently, numerous placental membrane-based wound healing and tissue repair products are commercially available, including:
EpiFix®, Grafix®, Life Patch®, AmnioExcel®, AmnioBand®, HSAM®, NEOX®1K, AMNIODERM+®, NuCel®, AmnioFIX®, ProKera Plus®, Visio-AMTRIX®, Orion™, Clarix® 1k, Omnigen®, PalinGen Flow®, AMEED®, AmnioCore, and BioXclude®.

The Layers of the Placental Membranes

Surgical Applications of Amniotic Membrane and Chorion in Regenerative Medicine.

Skin Repair

Placental membranes have been extensively used in dermatology to treat both acute and chronic skin wounds, including skin graft donor sites, diabetic foot ulcers (DFUs), venous leg ulcers, neuropathic ulcers, pressure sores, and burns. Effective wound management involves infection prevention, promotion of tissue regeneration, achievement of wound closure, and regulation of scar formation and remodeling.

Various wound care products are available, including basic protective layers, hydrogels, dressings infused with bioactive compounds, and synthetic skin substitutes, all designed to facilitate wound closure and healing. Numerous amniotic membrane (AM)-derived scaffolds have been developed in the United States and are currently undergoing clinical trials for dermatological applications.

Skin Graft Donor Sites

The use of AM in split-thickness skin graft donor sites has been evaluated. This reconstructive technique is frequently employed to promote healing in cases of burns, chronic ulcers, and tissue loss due to trauma or surgery, creating a secondary surgical site (the donor site).

An ideal dressing for donor sites should promote rapid healing, minimize pain and infection, prevent hypertrophic scarring, be easy to handle, and remain cost-effective. A meta-analysis with 219 patients demonstrated a significant improvement in healing time (mean difference −3.87 days) and healing rate (RR = 1.61) when AM was used compared to the standard of care. A separate clinical study confirmed the benefits of biological over non-biological dressings, although no significant differences were found in infection rates or pain relief.

Orthopedic Applications

The use of AM in orthopedic medicine is an emerging area of clinical investigation and use.  AM has also been used in flexor tendon repair surgery to promote healing and prevent adhesions. In a study involving 89 patients, freeze-dried AM was applied to wrap the severed tendon ends. The findings supported AM as a safe, effective, and absorbable biological barrier that reduced the incidence of postoperative tendon adhesions, a common complication. 

Applications in Other Surgical Fields

AM has also been successfully utilized across various surgical specialties due to its pro-healing properties, biocompatibility, and safety profile.

Nerve Repair

The reconstruction of peripheral nerves following injury remains a surgical challenge. Ideal nerve repair aims to restore both motor and sensory function. Current strategies include direct nerve repair with autografting, the gold standard, and the use of engineered tissue conduits, which have shown comparable effectiveness for gaps exceeding 4 cm.

While clinical applications of AM in nerve repair are still limited, several studies have demonstrated its potential. Wrapping the injury site with AM at the end of surgery has been shown to reduce scar tissue formation, prevent adhesion, and enhance functional recovery. AM also protects against endoneurial inflammation.

A tubulization technique combining amnion and muscle grafts was tested in five patients with median nerve damage at the wrist with gaps over 4 cm. Nerve regeneration was observed within one week, and the appearance of myelinated fibers was noted after three weeks, indicating early signs of functional restoration.

Removing Placental Membranes

Conclusion

Human placental membranes, particularly the amniotic membrane (AM) and chorion, offer a biocompatible scaffold enriched with collagen, growth factors, and antimicrobial peptides that support all phases of wound healing. These membranes help reduce inflammation, minimize scarring, and lower the risk of infection. Clinically, they have demonstrated significant benefits in promoting ulcer closure, accelerating epithelialization, and improving outcomes in burns, chronic wounds, and ocular injuries.

The next-generation products such as solubilized AM hydrogels and dehydrated membrane formulations, are being developed to improve shelf life, ease of application, and bioactivity retention. 

If you’re experiencing symptomatic degenerative joints or are exploring regenerative options for your recovery, University Orthopedic Care offers cutting-edge treatments grounded in the latest advancements in regenerative medicine.

Call us at (866) 961-1744 to schedule a consultation with one of our board-certified physicians and discover personalized solutions to support your healing journey.