We've worked with hundreds of clinicians across the Southwest over the past several years, and we've learned one thing with absolute certainty: the single most important predictor of whether an advanced biologic wound dressing will succeed or fail isn't the product itself. It's the wound bed you're applying it to.
This distinction matters enormously. We've seen the same fish skin graft fail on an improperly prepared wound and succeed spectacularly on an adjacent case where the clinician took time to prepare the bed correctly. The difference isn't the product quality—it's tissue readiness.
This article walks you through the evidence-based framework we use to evaluate wound readiness, the debridement strategies that matter most, and the practical preparation protocols that maximize outcomes. If you're deploying advanced biologics as a standard part of your wound care practice, mastering this foundation is non-negotiable.
The TIME/TIMERS Framework: The Industry Standard for Wound Assessment
The TIME framework emerged from clinical consensus in the early 2000s as a structured approach to wound bed evaluation. It stands for Tissue, Inflammation/Infection, Moisture, and Epithelial edge. The expanded TIMERS version adds Regeneration and Social factors[DOI]. This isn't theoretical—it's the foundation most health systems use to determine readiness for advanced interventions.
Understanding this framework is essential because Medicare and most payers now expect documented evidence that you've applied systematic wound assessment before deploying higher-tier interventions like biologic grafts. When an auditor looks at your chart, they're asking: did you follow a structured assessment protocol, or did you simply apply an expensive product because the patient's wound wasn't healing?
Tissue Assessment: The Foundation
The first pillar of wound readiness is tissue composition. A wound bed ready for biologic integration must contain primarily granulation tissue, not necrotic tissue, slough, or eschar.
Here's what we mean by each:
Necrotic (black) tissue is dead cellular material that prevents angiogenesis and cell migration. It's a physical barrier to healing. If more than 25% of the wound bed is covered in necrosis, the wound simply isn't ready for biologics. The product will be applied over dead tissue, and integration won't occur.
Slough (yellow) is devitalized tissue that's partially separated. It needs to come off before biologic application. This is where the debridement decision tree matters most.
Granulation tissue (beefy red) is what you're looking for. It indicates active angiogenesis and is the appropriate substrate for biologic integration.
The Five Debridement Modalities: When to Use Each
Debridement isn't one-size-fits-all. Clinical evidence supports different approaches depending on wound characteristics, patient factors, and clinical urgency.
Surgical Debridement is the gold standard for rapid, complete removal of necrotic tissue. It's especially indicated when you're dealing with thick eschar, large necrotic burden, or signs of advancing cellulitis. Surgical debridement allows you to see the wound bed clearly and remove unhealthy tissue definitively. For wounds with significant necrotic burden, this is your most efficient pathway to wound readiness. The downside: it requires operating room time and carries anesthesia risk.
Sharp (Mechanical) Debridement at bedside is faster than surgical debridement but requires skill and patient tolerance. It's appropriate for slough-predominant wounds where the necrotic tissue is loosely adhered. Your PT team or wound nursing staff can perform this, making it practical for frequent assessment intervals. This is what most outpatient wound centers rely on.
Autolytic Debridement relies on the body's own enzymes to break down necrotic tissue. Moisture-rich environments accelerate this process. Hydrogels, alginates, and hydrocolloids all support autolytic debridement. The advantage: it's non-traumatic and suitable for patients who can't tolerate active debridement. The disadvantage: it's slow. For a patient with 2-3 weeks until their biologic appointment, autolytic debridement is reasonable. For someone scheduled for grafting in 5 days with significant eschar, it won't cut it.
Enzymatic Debridement uses topical enzyme products (like collagenase) to selectively break down collagen in necrotic tissue while sparing healthy granulation. The evidence is solid—multiple RCTs show enzymatic debridement accelerates tissue removal when combined with manual removal of loosened debris. This is often our preferred approach for slough-heavy wounds on patients who can't tolerate sharp debridement. Cost is meaningful but often justified by faster healing progression.
Biologic Debridement (sterile larvae therapy) is underutilized in clinical practice but has compelling evidence. Certain species of fly larvae selectively consume necrotic tissue without damaging healthy tissue. For clinicians experienced with this approach, it's remarkably effective. It's rarely needed in standard practice but is worth knowing about for difficult cases.
The practical approach we recommend: assess necrotic burden and patient factors, then sequence debridement methods. For a patient with thick eschar and good performance status, schedule surgical debridement. For a stable patient with slough-predominant wounds, start with sharp debridement at clinic visits plus enzymatic support between visits. For a frail patient, autolytic support with manual removal as tolerated.
Infection and Inflammation: The Hidden Wound Killer
This is where we see the most common errors in practice. Clinicians sometimes apply biologics to wounds that have uncontrolled infection or excessive biofilm burden, then are surprised when integration fails.
The distinction between localized infection and systemic infection is clinically crucial. A wound with elevated bacterial counts and localized inflammation (warmth, increased drainage) but stable vitals and no fever may respond to topical antimicrobial management without systemic antibiotics. Topical silver, iodine-based products, and antimicrobial dressings can control biofilm effectively when infection is local.
But if the patient has fever, lymphadenopathy, elevated WBC, or systemic signs, you need systemic antibiotics before considering biologics. A biologic graft applied to an actively infected wound will fail. The infection will prevent integration and waste product.
The biofilm question is subtler. Most chronic wounds have biofilm—a structured community of bacteria protected by extracellular matrix. Standard bacterial cultures won't detect biofilm because the organisms aren't in planktonic form. Histopathology is the gold standard for biofilm assessment, but most practices don't routinely perform this.
Here's the clinical principle: if a wound has been static for 4+ weeks despite standard care, assume biofilm is a factor. Mechanical disruption (sharp debridement, irrigation) helps break biofilm architecture. Adding enzymatic debriders and antimicrobial dressings creates an environment hostile to biofilm regrowth. We've observed that 2-3 weeks of aggressive biofilm management before biologic application significantly improves outcomes versus applying the graft immediately.
Moisture Balance: The Goldilocks Problem
Too dry and the wound desiccates, halting cell migration. Too wet and you get maceration, increased bacterial proliferation, and periwound breakdown. The biologic you're applying needs an environment with optimal moisture—moist enough for cell migration and angiogenesis, not so wet that the surrounding tissue breaks down.
Most modern dressings are designed around moisture balance principles. Alginates and foams absorb moderate exudate while maintaining moisture. Hydrogels add moisture to dry wounds. Antimicrobial foams and alginates provide both moisture management and infection control.
Before biologic application, the wound should have balanced exudate—enough that the wound bed looks moist and granulation is visible, but not so much that it's saturating gauze every 4 hours. If a wound is heavily exudative, you need to understand why: Is it infection? Venous insufficiency? High protease activity? Address the root cause before you graft, or the same environment will challenge your biologic.
Epithelial Edge: The Margin Migration Question
Here's the critical teaching point that separates evidence-based wound management from product-driven medicine: is the epithelial margin migrating? If edges are advancing, the wound is responding to standard care. If they've been static for 4+ weeks despite optimal pressure management, infection control, and moisture balance, then the wound has become chronic and may benefit from biologic augmentation.
The endpoint we're looking for is wound readiness—a wound bed that's clean, free of infection, adequately perfused, and prepared for the biological demands of integrating a graft. For fish skin products like Kerecis, you want clean granulation tissue that will accept the graft and support angiogenic integration. For spider silk dressings like SYLKE, you want an environment where the dressing can manage exudate while maintaining moisture and allowing cell migration.
Practical Preparation Protocols Before Fish Skin and Spider Silk Application
Here's where the framework translates to clinic reality. The protocols we recommend differ slightly between product types because the biological mechanisms differ.
Before Kerecis Fish Skin Application
Fish skin grafts require integration with host tissue. The allogeneic graft needs to be vascularized and incorporated. This demands a wound bed that's ready to accept and integrate the graft.
Minimum 72 hours before application: Sharp debridement to remove all slough and minimize necrotic burden to less than 10% of wound surface. Fish skin works best on clean granulation tissue.
Minimum 48 hours before application: Culture or swab if infection is suspected. If bacterial counts are elevated but no systemic signs, apply topical antimicrobial support. If systemic signs are present, delay grafting until antibiotics have achieved 48-72 hours of systemic coverage.
Day of application: Irrigate thoroughly with normal saline to remove bioburden. Pat dry gently. The wound should be moist but not dripping—this is the ideal substrate for graft integration. Apply the fish skin graft as specified in the product protocol. Most fish skin grafts are sutured or stapled initially, then covered with a non-adherent dressing.
Post-application care: Minimize disruption for the first 10-14 days to allow integration. Graft take is typically assessed at 2-3 weeks when you first lift the dressing. Full integration takes 3-4 weeks.
Before SYLKE Spider Silk Application
Spider silk dressings function differently—they're not grafts that need vascularization and incorporation, but rather an advanced dressing matrix that manages moisture, provides antimicrobial activity, and facilitates epithelialization. This means the preparation is somewhat less stringent.
Minimum 48 hours before application: Remove gross slough and obvious necrotic material. Spider silk dressings can be applied to wounds with light slough as long as heavy bioburden isn't present. The dressing itself has antimicrobial properties that can help control biofilm in the early post-application phase.
Infection status: Assess for systemic infection, but localized biofilm is less of a contraindication for spider silk application than for fish skin grafting. The dressing's antimicrobial properties mean it can be part of your biofilm management strategy rather than something that requires pre-treatment.
Day of application: Clean the wound gently. Spider silk can be applied to moderate exudate—in fact, the dressing's moisture-handling properties mean it performs well in exudative wounds. This is actually a practical advantage in many diabetic and venous ulcer cases where exudate is persistent.
Common Mistakes That Waste Product and Worsen Outcomes
We've documented these repeatedly in the field, and they're entirely preventable with proper planning.
Mistake 1: Applying biologics to insufficiently debrided wounds. If the wound still has significant slough or necrotic tissue, integration won't occur. You've wasted a graft and demoralized the patient. Spend the time and resources upfront to get the bed clean.
Mistake 2: Applying biologics in the presence of active systemic infection. The infection will consume resources that should go to graft integration. Delay grafting until infection is controlled. This isn't a setback—it's appropriate clinical sequencing.
Mistake 3: Applying biologics without understanding root cause. If the wound isn't healing, something is wrong. Is it pressure? Perfusion? Infection? Continued trauma? If you don't address the root cause, the biologic will fail and the underlying problem will persist. Biologics augment healing—they don't replace fundamental wound management principles.
Mistake 4: Inadequate post-application immobilization and dressing. The product's success depends on the weeks immediately after application. If you don't protect the graft adequately, the patient will disrupt it (often unintentionally), and integration won't occur.
Documentation for Medicare Coverage and Payer Requirements
The Centers for Medicare & Medicaid Services and private payers now expect documented evidence of wound assessment and failed conservative care before approving biologic products. Here's what your documentation needs to include:
TIME/TIMERS Assessment: Document tissue composition (percentage necrotic, slough, granulation), infection status, moisture level, and epithelial margin status. This shows you followed a systematic framework.
Failed Conservative Care Duration: Document the timeline. How long has the wound been treated with standard care? Most payers expect minimum 30 days of documented conservative care (pressure management, moisture balance, infection control, debridement as needed) before advancing to biologics.
Debridement Documentation: Record type, frequency, and response. This creates a timeline showing progressive improvement or stasis.
Wound Measurements: Length, width, depth, and area. Photograph before debridement and before biologic application. This provides objective evidence of wound status.
Infection Assessment: Document culture results if available, or clinical assessment of infection risk. Document any systemic or local antimicrobial therapy.
Medical Necessity Statement: A 2-3 sentence summary explaining why the biologic is appropriate for this specific wound at this specific time. "Patient's [chronic diabetic/venous] ulcer has failed 6 weeks of optimized standard care including [specific interventions]. The wound demonstrates [current tissue status], requiring advanced biologic support to achieve closure."
This documentation isn't busy work—it's the foundation for coverage decisions and, increasingly, the audit trail that protects your practice.
The Practical Readiness Checklist
Before you reach for the biologic product, use this checklist:
- Is the wound bed primarily granulation tissue (>75%)? YES / NO
- Have you performed or documented debridement within the past 72 hours? YES / NO
- Is the patient afebrile with normal vitals and no signs of systemic infection? YES / NO
- Have you addressed any localized biofilm burden? YES / NO
- Is the moisture balance appropriate—moist granulation visible, but not macerated periwound? YES / NO
- Has the epithelial margin been static for 4+ weeks despite optimized standard care? YES / NO
- Do you have photographs and measurements documenting the wound? YES / NO
- Have you documented at least 30 days of conservative care? YES / NO
- Have you communicated the treatment plan and realistic expectations to the patient? YES / NO
If you can answer yes to all nine questions, the wound is ready. If you're answering no to any of them, spend the additional time preparing the wound bed. The outcome difference is dramatic.
Closing Thoughts: Preparation is the Real Intervention
Advanced wound care biologics are powerful tools. But they work best when deployed in a scientifically prepared environment. The TIME/TIMERS framework gives you the language and structure to assess readiness systematically. The debridement modalities give you the tactical options to remove barriers to healing. And the preparation protocols give you the specific workflows to maximize integration and outcomes.
We work with practices that have learned to sequence their interventions—starting with the fundamentals, building to biofilm management and infection control, then deploying biologics into a prepared bed. Those practices see consistent outcomes. They see graft take. They see wounds closing. And they see satisfied patients who healed the first time.
If you'd like to discuss preparation protocols for your specific wound types or patient population, our team is here. We've documented what works, and we're invested in helping your practice build a sustainable advanced wound care program.